IADVL
Indexed with PubMed and Science Citation Index (E) 
 
Users online: 4182 
     Home | Feedback | Login 
About Current Issue Archive Ahead of print Search Instructions Online Submission Subscribe What's New Contact  
  Navigate here 
  Search
 
  
 Resource links
   Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
   Article in PDF (796 KB)
   Citation Manager
   Access Statistics
   Reader Comments
   Email Alert *
   Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
    Introduction
Vaccines for Vir...
Vaccines for Bac...
Vaccines for Tre...
Vaccines in Immu...
Vaccine-Induced ...
Conclusion and F...
   References
   Article Tables

 Article Access Statistics
    Viewed5416    
    Printed184    
    Emailed0    
    PDF Downloaded848    
    Comments [Add]    

Recommend this journal

 


 
 Table of Contents    
REVIEW ARTICLE
Year : 2018  |  Volume : 84  |  Issue : 4  |  Page : 388-402

Updates on the use of vaccines in dermatological conditions


1 Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
2 Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
3 Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
4 Department of Dermatology, American University of Beirut Medical Center; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon; Department of Dermatology, Columbia University, New York, USA

Date of Web Publication22-May-2018

Correspondence Address:
Mazen Kurban
Department of Dermatology and Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdvl.IJDVL_1036_16

Rights and Permissions

  Abstract 


Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.


Keywords: Genetics, immunotherapy, vaccines


How to cite this article:
Hanna E, Dany M, Abbas O, Kreidieh F, Kurban M. Updates on the use of vaccines in dermatological conditions. Indian J Dermatol Venereol Leprol 2018;84:388-402

How to cite this URL:
Hanna E, Dany M, Abbas O, Kreidieh F, Kurban M. Updates on the use of vaccines in dermatological conditions. Indian J Dermatol Venereol Leprol [serial online] 2018 [cited 2019 Oct 16];84:388-402. Available from: http://www.ijdvl.com/text.asp?2018/84/4/388/232981





  Introduction Top


Vaccines are among medicine's greatest achievements and most successful strategies to prevent diseases. Not only have they helped eradicate smallpox, but they also prevent around 2–3 million deaths every year from diphtheria, tetanus, pertussis and measles.[1] The concept of vaccination entails improving immunity to a specific disease. This is accomplished by introducing a weak form of the disease-causing agent, an antigen, which induces a specific immune response to produce specific types of antibodies. When the actual disease antigens are introduced to the body of a vaccinated individual, the pre-formed antibodies produced in response to the vaccine are already present and they either prevent the disease from happening or help in diminishing the severity of the disease presentation.

The World Health Organization recommended, through its Expanded Program on Immunization in 1961, inclusion of vaccines for preventable diseases in the national health programs of countries. Since then, there was increasing worldwide recognition of the role of vaccines in limiting the spread of infectious diseases in the community. India, for example, has expanded its immunization efforts and has strategically introduced several new vaccines in its adopted Universal Immunization Program, with 42% of spending on routine vaccination being made by the Indian government itself.[2],[3]. As a result, the under-five mortality rate has dropped from 233 to 63 per 1000 over the last 5 decades.

Due to the recent developments in the medical field, immunotherapy has not only played a pivotal role as a cost-effective public health intervention for prevention of infectious diseases but also has surged as an attractive method aimed at treating and preventing other types of diseases, including malignancy, autoimmune disorders and allergies. In fact, the identification of specific antigens and immunological epitopes has allowed the creation of vaccines derived from multiple types of antigen sources including glycolipids, tumor-associated antigens, dendritic cells, autologous and allogeneic peptide antigens.[4] Such vaccines are actively being developed and tested in multiple ongoing clinical trials to target a wide variety of diseases. This review aims at summarizing the use of vaccines in dermatological diseases.


  Vaccines for Viral Infections Affecting the Skin Top


Skin infections are very common. Some are primary, such as herpes simplex virus, human papillomavirus, varicella/zoster or leishmanial infections. Other infections can have secondary skin manifestations such as measles, rubella, human immunodeficiency virus, cutaneous tuberculosis and Lyme disease.

Interestingly, the first vaccine (vaccinia-cowpox) for immunization was developed to prevent smallpox, a highly contagious and fatal blister-forming infection. The vaccine was introduced by Edward Jenner in 1798 and allowed the worldwide eradication of this deadly disease in 1980.[5] The great success of this global immunization campaign led by the World Health Organization in 1967 urged researchers to develop further vaccines for both prophylaxis and treatment of certain diseases.

Human papillomavirus infection

Infection with high-risk human papillomaviruses, particularly human papillomavirus types 16 and 18, promotes the development of genital warts and cervical, anal and oral cancers.[6] This represents a substantial public health burden. Indeed, cervical cancer is a major cause of cancer deaths in women.[7] Men are also at a risk of human papillomavirus-associated verrucae and cancers, especially anal and penile cancer. The incidence of human papillomavirus-associated genital cancers is particularly high in men who have sex with men, suggesting an acute need for prevention in this population.[8]

Three human papillomavirus vaccines are currently available. The bivalent/2vHPV vaccine (Cervarix) by GlaxoSmithKline protects against human papillomaviruses16 and 18. The quadrivalent/4vHPV vaccine (Gardasil) by Merck covers strains 6, 11, 16 and 18. Finally, the 9-valent/9vHPV vaccine (Gardasil 9) by Merck produces immunity against human papillomavirus types 6, 11, 16, 18, 31, 33, 45, 52 and 58. Any of these vaccines can be used in females.[8],[9],[10] According to the Advisory Committee on Immunization Practices, it is recommended that females between ages 11 and 12 are vaccinated with three doses of the human papillomavirus vaccine. These can be given to females as young as 9 years and to those whose ages range between 13 and 26 as well who have not been previously vaccinated. There is no need to test by  Pap smear More Details or human papillomavirus DNA or antibodies prior to vaccination. On the other hand, the American Cancer Society does not recommend routine vaccination for women older than 18 years because they are more likely to have been already exposed to human papillomavirus. Therefore, according to the American Cancer Society, this decision should be made on an individual basis. In addition, vaccination is also recommended below 26 years of age for men who have sex with men and immunocompromised individuals, including those with HIV infection, if they have not received the vaccine previously. At a population level, use of the 9vHPV vaccine was found to be more cost-effective compared with 4vHPV for both men and women.[8],[9],[10],[11] The human papillomavirus vaccines are generally well-tolerated with the most common side effects, reported in up to 50% of patients, being injection site pain, mild fever and injection site reaction.[12] [Table 1] includes the recommended immunization schedule for human papillomavirus vaccine with possible adverse events, and [Table 2] shows the available human papillomavirus vaccines and their price.
Table 1: Recommended immunization schedule for persons aged 21 years or younger

Click here to view
Table 2: List of available vaccines, their trade names and price*

Click here to view


Despite the benefits of the available human papillomavirus vaccines, controversy remains regarding whether their benefits outweigh the risks. This has led to resistance to implementation of these vaccines by some communities. Concerns about human papillomavirus vaccines have been led not only by people but also by some physicians and healthcare professionals. The most common reason lies in some studies that suggest mild documented adverse events with a positive risk-benefit assessment against human papillomavirus vaccines.[13],[14],[15] For example, a large systematic review, that included a total of 29, 540 individuals, showed that pain, swelling and fever were the most frequently reported events, in addition to mild headache, fatigue and gastrointestinal symptoms.[13] Interestingly, association between these vaccines and autoimmune manifestations has also been reported in some studies. However, recent reports have emphasized the importance of genetic background and previous history of adverse events to other vaccinations in developing autoimmune disease post human papillomavirus vaccination. Therefore, despite all the controversy, human papillomavirus vaccination remains the most effective way to prevent cervical cancer.[13],[14]

In addition to such controversies, there are several limitations that limit the successful implementation of human papillomavirus vaccines, especially in developing countries. Such limitations include high vaccine costs, lack of public awareness about cervical cancer and about early screening and detection and most importantly the nature of human papillomavirus transmission, which carries the stigma of unacceptable sexual behavior. In many communities, not only is human papillomavirus vaccine expensive but promotion of human papillomavirus vaccines may be perceived by some as promotion of promiscuity. In India, for example, the introduction of human papillomavirus vaccine clinical trials was met with strong resistance from civil society organizations who expressed their worries to the Indian Government.[16] Two important factors highly associated with increased acceptance of the human papillomavirus vaccine were community awareness of its benefits and understanding that all children are at risk regardless of religious or moral values. This emphasizes the importance of continuous efforts to break these barriers and to spread awareness of the importance of human papillomavirus vaccine in the prevention and control of communicable human papillomavirus infections and malignancies.[17],[18]

While human papillomavirus vaccines resulted in significant achievement in terms of prevention of human papillomavirus infections and its associated diseases, there remains a great human papillomavirus-associated disease burden worldwide. In fact, to date, it is estimated that 5 million women are infected with human papillomavirus worldwide that carry a risk for developing invasive cervical cancer. In India, for example, the annual incidence of cervical cancer is approximately 130,000 cases with 75–80,000 deaths, which makes about one-fourth of the global cervical cancer burden. As a result, there is a need to develop therapeutic human papillomavirus vaccines for better control and eradication of existing human papillomavirus-associated diseases.[16],[17],[18]

Multiple types of therapeutic human papillomavirus vaccine candidates have been developed and are being tested in pre-clinical studies and clinical trials. These include live vector, protein/peptide, nucleic acid and cell-based vaccines. The rationale behind designing these vaccines lies in targeting the E6 and E7 oncoproteins. These are constitutively expressed by human papillomavirus-associated tumors and are important for the introduction and maintenance of cellular transformation by human papillomavirus-infected cells and result in activation of cytotoxic T cells.[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35] These vaccines have shown promising results in clinical trials involving patients with human papillomavirus-related infections and malignancies. The vaccine candidate HPV-16 SLP, for example, has been shown to be safe and highly immunogenic and resulted in significant enhancement of CD8 positive T cell response to E6 and E7 in patients with genital warts who were vaccinated as compared to placebo recipients.[21],[36] In addition to genital warts, therapeutic human papillomavirus vaccines candidates have been tested with mild success in human papillomavirus-associated malignancies, including vulvar intraepithelial neoplasia and vaginal intraepithelial neoplasia. In a clinical trial by Baldwin et al., vaccination with therapeutic HPV vaccine (TA-HPV) candidate resulted in 50% reduction in lesion diameter over a six-month period in 5 out of 12 patients, and one patient had complete response.[21],[36] Details regarding therapeutic human papillomavirus vaccine candidates are listed in [Table 3].
Table 3: List of therapeutic human papilloma viruses vaccine candidates

Click here to view


Herpes simplex virus

Herpes simplex viral infections are some of the most ubiquitous of all infections, with prevalence in the United States ranging from 65% for herpes simplex virus-1 and 16% for herpes simplex virus-2.[37],[38] Prevalence varies among different countries. India for example, has herpes simplex virus-2 infections ranging between 11.4 and 28.82% in retrospective data analysis studies.[39] Herpes simplex virus-2 seroprevalence ranges between 43 and 83% among sexually transmitted diseases patients and between 7.9 and 14.6% in population-based cross-sectional studies. Herpes simplex virus-1 seroprevalence, on the other hand, ranges between 36.5 and 92.5% in cross-sectional studies.[40],[41] Given that significant morbidity and mortality are associated with those viruses and that antiviral medication have a minimal impact on prevalence, numerous efforts have been made to develop an efficacious vaccine. Multiple strategies are being studied now for eventual development of a herpes simplex virus-2 vaccine, especially that reducing genital herpes would be expected to reduce HIV spread.[42]

While no effective vaccines against herpes simplex virus infection are available yet, multiple vaccine candidates have been tested in the preclinical phase on animals and are being studied in clinical trials.[37],[43] [Table 4] shows a list of herpes simplex virus vaccine candidates and their current developmental status.
Table 4: List of herpes simplex virus vaccine candidates

Click here to view


To date, the largest clinical trial of a herpes simplex virus vaccine candidate was the Herpevac trial, which studied the efficacy of herpes simplex virus-2 gD vaccine against herpes simplex virus disease in herpes simplex virus-1 and herpes simplex virus-2 seronegative patients. Interestingly, the vaccine, which consisted of glycoprotein D from HSV-2 with 3-O-deacylated monophospholipid A (MPL) adjuvant, provided 35% efficacy against herpes simplex virus-1 disease and 58% efficacy against herpes simplex virus-1 genital disease, but was not efficacious against herpes simplex virus-2 acquisition.[44] Within the past 3 years, four additional herpes simplex virus vaccine candidates have entered into phase II trials as therapeutic vaccine candidates. These have novel adjuvants which stimulate T cell immunity. GEN-003, a subunit vaccine consisting of glycoprotein D2 and Infected Cell Protein 4 (GD2-ICP4) with Matrix M adjuvant, showed a 50% decrease in genital HSV-2 shedding rate after the therapeutic vaccine series.[45],[46],[47] Another candidate was HerpV, a 32 peptides vaccine linked to heat shock protein and QS-21 adjuvant. It showed a 15% decrease in viral shedding up to 6 months after the initial vaccine series.[48] VCL-HB01/HM01, a plasmid DNA vaccine encoding glycoprotein D2 and Unique Long (UL)-46 protein adjuvanted with Vaxfectin®, a lipid-based formulation, has also shown a statistically significant reduction in genital lesion rate compared to baseline. Interestingly, HSV529, a live attenuated herpes simplex virus-2 that is replication defective with deletion of UL-5 and UL-29 proteins, is currently in phase I trials and is being studied as both therapeutic and preventive vaccine candidate.[49]

On the other hand, several vaccine candidates are currently undergoing pre-clinical experiments on animals, mostly mice and guinea pigs. These include Glycoprotein D2/Glycoprotein C2/Glycoprotein E2, HSV-2 0 ΔNLS, HF10, ΔGlycoprotein D2, AD472, CJ2-Gd2, Inactivated herpes simplex virus-2 in MPL, HSV-1 Glycoprotein B Lentiviral vector and Glycoprotein B1s-NISV.[50],[51],[52],[53],[54],[55] Details regarding these vaccines are delineated in [Table 3].

Varicella-zoster virus

Varicella-zoster virus causes both varicella, also known as chickenpox, and herpes zoster, also known as shingles. Not only did the introduction of the varicella vaccine in 1984 lead to a marked decrease in the incidence of chickenpox and shingles but it also resulted in a significant drop in varicella-related hospitalization to 14.5 per 100000 cases worldwide. In fact, the World Health Organization recommends that, in countries where varicella is an important public health burden, its vaccine should be introduced into their routine immunization programs. As a result, varicella vaccine was added to the immunization schedule by the Indian Academy of Pediatrics in 2011, and its incidence has dropped by almost 50%.[56],[57],[58]

[Table 1] includes the recommended immunization schedule for varicella vaccine with possible adverse events, and [Table 2] shows the available varicella vaccines and their price. The immunization schedule consists of a first dose at 12–18 months followed by a second dose between 4 and 6 years of age. The second dose can be administered 3 or more months following the first dose in children below 4 years of age.[59] Breakthrough varicella is defined as chickenpox occurring more than 42 days after vaccination. It is manifested by atypical features with fewer and predominantly maculopapular lesions. This entity was initially reported in 2 to 4% of cases per year with a recently reported 14% cumulative incidence over 7 years. Interestingly, the time from varicella vaccination was the most important risk factor for breakthrough varicella.[60]

Measles-mumps-rubella

Another pivotal vaccine that prevents two dermatologic entities is the measles-mumps-rubella vaccine, which was combined in 1971. Vaccination against measles led to a 75% decrease in deaths from 2000 to 2013 according to the World Health Organization. As the vaccination programs got incorporated globally, the number of reported rubella cases decreased from 135,947 in 1998 to less than 1,000 cases in 2003 according to the National Center for Infectious Diseases.[61] Despite it being no longer endemically transmitted in the United States, rubella continues to be endemic in several parts of the world, and only two World Health Organization regions – European and American regions – have established rubella elimination goals for the year 2010.[62] This emphasizes the need for accelerating measles-mumps-rubella vaccination campaigns in other areas such as south Asia. For example, a study from Jammu in India showed that 32.7% of girls aged between 11 and 18 were not immune to rubella.[63]

The measles-mumps-rubella vaccine can be administered in combination with varicella as a tetravalent vaccine, the measles-mumps-rubella-varicella vaccine. Some reports showed an increased risk for febrile seizures with this combined vaccine, and thus preference was expressed for use of separate varicella vaccination only for the first dose.[64] Although varicella is considered to be a benign disease, the burden of varicella with its associated morbidity and mortality, has proven the vaccine to be cost-effective.[65] The live zoster vaccine, Zostavax®, was approved in 2006 for prevention of shingles and post-herpetic neuralgia in immunocompetent people aged more than 60 years.[65] This vaccine contains 14-fold more virions than the varicella vaccine.[66] However, the efficacy of this live attenuated zoster vaccine was shown to decrease within 5 years' post-vaccination, mandating the need for proper patient education regarding its safety and efficacy. In general, the zoster vaccine is well-tolerated causing minimal systemic side effects and mostly mild-to-moderate symptoms at the injection site. In addition, vaccinated individuals aged 60 to 69 years were shown to be more susceptible to such adverse events when compared to those aged 70 years or above.[66] [Table 1] includes the recommended immunization schedule for measles-mumps-rubella vaccine with possible adverse events, and [Table 2] shows the available measles-mumps-rubella vaccines and their price.

Not only has measles-mumps-rubella vaccine proven to be efficacious in the prevention of measles, mumps and rubella, it also showed promising results when used for other diseases, namely recalcitrant warts and molluscum contagiosum. The hypothesis behind this was that it can result in induction of cellular immune response, which can accelerate the destruction of virus and virus-infected host cells. Being recurrent and often resistant to treatment, warts represent a frustrating challenge for both patients and physicians. Studies have shown that intralesional immunotherapy by measles-mumps-rubella vaccine is a promising, effective and safe treatment modality for warts.[67] Nofal et al. evaluated this vaccine in a randomized placebo-controlled trial and noted complete response in 81.4% of patients as compared to 27.5% in the placebo group.[68] Although we could not find clinical trials that study measles-mumps-rubella vaccine in molluscum contagiosum, we found two case reports in which successful treatment was reported.[69]

Human immunodeficiency virus

HIV had a prevalence of 0.8% in 2015 with 36.7 million people living with the virus worldwide.[70] Ever since its identification as the cause of acquired immunodeficiency syndrome (AIDS) in 1984, significant advancement has been made towards its prevention and treatment. Interestingly, India, which has the third largest HIV epidemic in the world after South Africa and Nigeria, had a 32% decline in new HIV infections between 2007 and 2015.[71] Despite this improvement, the quest for developing an HIV vaccine that can be therapeutic and preventive remains of significant importance to public health.

Although there is no Food and Drug Administration-approved vaccine to date, multiple candidates have been studied in pre-clinical experiments and clinical trials. The first HIV vaccine candidates consisted of recombinant subunit vaccines that mimic the viral envelope protein gp120 and its precursor gp160 in the hope that they would prevent HIV from entering human cells. These were the basis for the AIDSVAX vaccines. Two recombinant gp120 vaccine, bivalent subtype B/B and bivalent subtype B/E, could reach phase III clinical trials testing, but both failed to prove efficacious.[72],[73],[74],[75],[76],[77],[78] Following the failure of recombinant envelope vaccines, attempts at developing vaccines that can induce immune responses that would achieve cross-strains immunity began. These vaccines began with the replication-defective recombinant Ad5 vector with HIV-1 clade B gag/pol/nef inserts. It was designed to induce a CD8+ T-cell response to HIV-1 in the hope that immunity would be directed at conserved regions of HIV and would be effective against its different clades. While pre-clinical studies showed promising immunogenicity, two phase II clinical trials, STEP and Phambili, were stopped after interim efficacy analysis. The STEP study, conducted among men who have sex with men, showed that vaccine recipients had an increased risk of HIV-1 acquisition. Phambili, conducted in heterosexual adults, showed no vaccine effect on HIV acquisition during blinded follow-up but increased risk of HIV-1 acquisition during the unblinded follow-up.[76],[77] Following the Adenovirus 5 (Ad5) vector vaccine was the prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine. It was designed to elicit HIV-specific, multifunctional responses in CD4+ and CD8+ T-cells and antibodies to envelopes of the major circulating strains. The vaccine is a 6-plasmid mixture encoding HIV envelope glycoprotein (env) from subtypes A, B and C and subtype B gag, pol and nef proteins, and rAd5 vector expressing identical genes, with the exception of nef. The HIV Vaccine Trials Network conducted a phase II trial of this vaccine in men or transgender women who have sex with men and showed lack of efficacy in reducing the rate of acquiring HIV-1 infection (W).[53] Interestingly, Canarypox ALVAC-vCP1521 vaccine is the only vaccine to date that has proven efficacious in reduction of HIV-1 acquisition rates in both pre-clinical studies and phase III clinical trials that are still ongoing.[73],[74] The RV144 trial, a multicenter, double-blind phase III trial, demonstrated 60% efficacy over the first year compared with placebo.[79] Although there is not yet a Food and Drug Administration-approved HIV vaccine, these results are encouraging for the future development of a successful HIV vaccine.[80]

In addition to preventive vaccines, vaccine developers have recently experimented therapeutic vaccine candidates that can be used as adjunctive treatment to highly active antiretroviral therapy. Tat vaccine, which consists of antibodies against HIV-1 transactivator of transcription (Tat) protein, have shown a statistically significant reduction of blood HIV-1 DNA load that persisted for up to 3 years post-vaccination.[81] Another therapeutic vaccine candidate was AGS-004, which is a personalized vaccine consisting of patient-derived dendritic cells and HIV antigens. It is currently being studied in phase II clinical trials.[82] [Table 5] shows a list of HIV vaccine candidates and their current developmental status.
Table 5: List of human immunodeficiency virus vaccine candidates

Click here to view



  Vaccines for Bacterial or Parasitic Infections Affecting the Skin Top


Propionibacterium acnes mediated acne vulgaris

The treatment of acne encompasses a wide variety of topical and oral agents ranging from antibiotics to retinoids. Interestingly, a research group from the University of California is currently investigating the use of vaccines for treating Propionibacterium acnes-associated diseases including acne vulgaris. This stems from the idea that cell wall-anchored sialidase of P. acnes or killed-whole organisms of P. acnes have been shown to induce in-vivo protective immunity against P. acnes along with downregulation of cytokine production.[83] Multiple other vaccines are currently being developed based on killed pathogens, cell wall-anchored sialidase, monoclonal antibodies to the Christie, Atkins, Munch-Peterson factor of P. acnes, anti-Toll-like receptors and antimicrobial peptides.[83]

Mycobacterium leprae

Caused by the bacterium Mycobacterium leprae, leprosy affects the skin, nervous system, respiratory tract and eyes and can result in disfigurement and disability in advanced stages. Interestingly, 58% of new annual leprosy cases in the world are from India. According to the latest published annual report of the National Leprosy Elimination Program, a total of 86,028 leprosy cases were reported up until April 1, 2016 for the year 2015–2016 in India.[84] While India has an ongoing national program for eradication of leprosy, the number of cases increased from 1, 25, 785 to 1, 27, 326 between 2014 and 2015.[84],[85] Even though multidrug therapy is the gold standard for treating leprosy, the use of vaccines has been suggested as immune-prophylactic and immunotherapeutic. M. leprae expresses a varied amount of surface-associated and secretory proteins such as lipoproteins, outer membrane proteins and secretory proteins that may be utilized as antigenic targets in vaccine development. In fact, recent clinical trialists and vaccine developers have employed live or killed whole mycobacteria, such as bacillus Calmette–Guérin, Indian Cancer Research Center bacilli and Mycobacterium w either alone or admixed with killed M. leprae.[86] Interestingly, an Indian research group recently identified a penicillin-binding protein, ML0018c, as a possible candidate which may elicit both cellular and humoral immune response in M. leprae-infected patients. This protein can be used for the development of a peptide-based vaccine conveying immunity against leprosy.[87]

A vaccine prepared from heat-killed M. welchii has shown very promising results in leprosy prevention and treatment. The vaccine was initially developed in 1990s and consisted of heated M. welchii, a cultivable, non-pathogenic and rapidly growing saprophyte. Clinical trials were initiated by the Indian Council for Medical Research institute in endemic areas in India, namely Madhya Pradesh, Orissa, Bihar, UP, West Bengal, Uttaranchal, Chhattisgarh and Jharkhand. Sharing a number of common B and T cell determinants with M. leprae, the vaccine significantly reduced the disease burden. Its efficacy was 70% tested over a 10-year period. The vaccine has gained approval as a therapeutic and preventive vaccine against leprosy from the Drug Controller General of India (DCGI), Central Drugs Standard Control Organization, the National Regulatory Body under the Ministry of Health and Family Welfare in India and the US Food and Drug Administration. Its inclusion in the treatment regimen not only accelerates bacterial clearance but also shortens the recovery period and is effective in patients who are slow responders to multidrug therapy.[84],[88],[89],[90],[91]

M. welchii vaccine was renamed M. Indicus Pranii (MIP). The new name was a combination of the site of isolation of the bacterial species from India (indicus), the founder of the National Institute of Immunology in India Professor Pran Talwar (pran ii) and the National Institute of Immunology India (nii in pra-nii). Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of the cases reported annually. However, the Indian government aims at eliminating leprosy by 2020.[92] As a result, the National Leprosy Elimination Program initiated in August 2016 the Leprosy Case Detection Campaign aiming at detection of all leprosy cases in the community and their treatment. M. indicus pranii is being used to vaccinate contacts of leprosy patients, and, along with multidrug therapy, for the treatment of leprosy patients. This vaccine may prove to be India's landmark step towards eradication of leprosy.[87],[93],[94] [Table 1] includes the M. indicus pranii vaccine as part of the immunization schedule with adverse events reported to date.

Lyme disease

Despite adequate clinical results, the only Food and Drug Administration approved vaccine for prevention of Lyme disease, LYMErix™, was withdrawn from the market 3 years after its initiation. This was mainly due to significant local effects at the injection site, 26.8% vs 8.3% in controls, as well as systemic symptoms, 19.4% vs. 15.1% in controls.[95] In the absence of a Lyme vaccine, efforts are being tailored towards developing a reservoir targeted vaccine. Ongoing trials done over a period of 1 year and 5 years have shown a reduction in Lyme disease prevalence ranging from 24 to 76%, respectively.[96] In addition, adverse events to Lyme vaccines were mild and transient including local reactions such as swelling, redness and pain.[96]

Cutaneous leishmaniasis

Given that 90% of Leishmania infections present as a localized cutaneous reaction,[97] dermatologists have sought after different treatment strategies for this mucocutaneous disease, including pentavalent antimonials, second-line pentamidine, amphotericin B, allopurinol and ketoconazole. Studies in mice have highlighted the role of dendritic cells as important inducers of a T-helper (Th) 1/cytotoxic T (Tc) 1 protective immunity against leishmaniasis.[97] This fact has allowed the development of multiple experimental prophylactic vaccines, using dendritic cells pulsed with parasite lysate,[98] recombinant parasitic proteins [99] or even adjuvants such as CpG oligodeoxynucleotide motifs promoting IL-12 release.[99] One vaccine containing killed Leishmania amazonensis was shown to be safe in phase II clinical trials, however, did not demonstrate efficacy in phase III trials.[100] The use of bacillus Calmette–Guerin vaccine for the treatment of cutaneous leishmaniasis has shown promising results in murine, canine and hamster models but is still in pre-clinical studies.[101]

Cutaneous tuberculosis

Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette–Guérin. It is characterized by numerous papulovesicular lesions, which can leave residual hypochromic scars upon healing. Bacillus Calmette–Guerin was initially introduced as a prophylactic agent against tuberculosis. The World Health Organization currently recommends that bacillus Calmette–Guerin vaccine should be administered to all those living in areas of endemic tuberculosis. In India, for example, the vaccine is part of the national immunization schedule and is administered directly after birth. [Table 1] includes bacillus Calmette–Guerin as part of the Indian Academy of Paediatrics immunization schedule with possible adverse events, and [Table 2] shows the available vaccines, their trade names and their price. Interestingly, it was noticed that the incidence of leprosy decreased markedly after administration of bacillus Calmette–Guérin vaccine, especially when used as an adjuvant to multidrug therapy in the treatment regimen compared to multidrug therapy alone.[102]

Owing to its beneficial effect in cutaneous tuberculosis and leprosy, which was most likely related to cell-mediated immune response, interest rose in using bacillus Calmette–Guerin vaccine as a therapeutic agent in other skin conditions, including warts, cutaneous leishmaniasis and oral lichen planus.[103] A total of 122 patients have received intralesional bacillus Calmette–Guérin vaccine as a treatment of warts in all studies published to date. Only one study was a single-blind, placebo-controlled study conducted on 154 patients divided into a control and placebo groups. Intralesional bacillus Calmette–Guérin vaccine proved to be an effective and safe modality for the treatment of viral warts. Most studies showed complete clearance of the warts within 6 weeks to 2.5 months.[104] Topical and intralesional bacillus Calmette–Guérin vaccine has also proven efficacious and safe in oral lichen planus when compared to triamcinolone. This suggests a possible role as a promising therapeutic alternative for erosive oral lichen planus, especially for those resistant to glucocorticoids.[105]


  Vaccines for Treatment of Skin Malignancies Top


Melanoma

According to the National Cancer Institute, the incidence of invasive melanoma in the United States was estimated to be about 73,870 cases in 2015, and one American dies of melanoma every hour. Melanoma treatment depends on the stage of the cancer. Early lesions (Stage 0 melanoma) are often cured by surgical excision alone. Stage II and stage III resectable melanoma are managed with surgery and lymph node resection. Stage III unresectable and stage IV are aggressively treated with chemotherapy, targeted therapy and recently immunotherapy.[106] The 10-year overall survival rate for advanced melanoma is improving but is still only 10–15%.[107]

The use of melanoma vaccines in the treatment of malignant melanoma is currently being intensely investigated. The use of such vaccines is reasonable given the antigenic differences between normal adult melanocytes and melanoma cells in addition to the resulting immune anti-melanoma response triggered by immunocompetent cells.[108] Melanoma vaccines have utilized many antigen sources such as peptide antigens, glycolipids, tumor-associated antigens and dendritic cells.[4] [Table 6] summarizes the different vaccines used in melanoma.
Table 6: Vaccines used for melanoma treatment

Click here to view


Experimental clinical trials with “melanoma vaccines” are currently in progress and few have shown significant benefit as adjuvants in the setting of high-risk melanoma. However, ongoing trials have been more promising, especially with the advances in the immunology of melanoma. One recent study demonstrated higher response rates and longer progression-free survival in advanced melanoma patients when gp100 vaccine was combined with interleukin-2 (IL-2) immune activating agent.[109] The median overall survival was also longer in the gp100+IL-2 group than in the IL-2 only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P = 0.06).[109]

Multiple types of antigen sources have been used in the production of melanoma vaccines including autologous/allogenic peptide antigens, glycolipids, tumor-associated antigens and dendritic cells.[4] Vaccines using tumor cell-derived antigens are divided into two categories – autologous and allogeneic vaccines. In autologous vaccines, the patient's tumor cells are used, thus providing a narrow antigen spectrum specific to a particular patient. Limitations to its use include limited amount of tumor tissue accessible for vaccine preparation, especially after complete resection of clinically evident disease. In a recent phase II clinical trial for metastatic melanoma, an autologous vaccine composed of tumor-derived heat shock protein peptide complexes gp96 was shown to induce an anti-melanoma, class I HLA-restricted T-cell-mediated immune reaction in a proportion of treated patients. However, of the 28 patients enrolled, only two had a complete response and only three had stable disease at the end of follow-up.[110]

Allogeneic vaccines may be more representative as they are composed of melanoma cells from other patients selected for a variety of shared antigens. Even though they may not contain all the tumor-associated antigens on the treated patient's tumor, they do allow for large-scale randomized trials. One studied allogenic vaccine is Canvaxin polyvalent cancer vaccine. The cumulative data for Canvaxin therapeutic cancer vaccine represent the largest phase II clinical trial of any cancer vaccine. The vaccine exhibited prognostic significance for patients with stage III and IV melanoma. However, a phase III clinical trial for stage III unresected and stage IV melanoma showed unfavorable results.

Another category of vaccines is composed of cell surface glycolipids such as gangliosides GD3 and GM2.[111] In a phase III clinical trial for stage II resected melanoma, adjuvant ganglioside GM2 vaccine was not shown to improve clinical outcome.[112]

In addition to the use of tumor cell-derived antigens and gangliosides, tumor-associated antigens have been integrated into vaccines and often combined with adjuvants such as GM-CSF. Melanoma specific tumor-associated antigens include Melan-A/MART-1, gp100, tyrosinase, tyrosinase-related protein-1 (trp-1) and tyrosinase-related protein-2 (trp-2).[113],[114]

Dendritic cells, being antigen-presenting cells specialized for the induction of a primary T-cell response, have also been explored for manufacturing vaccines in advanced melanoma. Mouse studies have shown that dendritic cells do induce antitumor immunity, and thus multiple studies aimed at demonstrating the clinical effect of such vaccines on the survival of melanoma patients have been done.[83] However, one study showed that vaccinating with peptide-loaded dendritic cells can result in long-term clinical response in only a minority of metastatic melanoma patients (2 out of 15 patients).[115] In addition, a recent phase I/IIa clinical trial in stage IV melanoma using autologous tumor–dendritic cell fusion (dendritoma) vaccine with low-dose interleukin-2 showed that overall survival was significantly higher in the experimental group (23.8 versus 8.7 months, P = 0.004).[116]

Another vaccine tested in melanoma is herpes simplex virus-1 oncolytic vaccine known as Talimogenelaherparepvec (T-VEC). T-VEC is designed to induce systemic antitumor immunity and was effective in increasing the response rate and survival (≥6 months) vs GM-CSF in a phase 3 melanoma trial.[117] A phase 1 trial studied its toxicity and showed that combining T-VEC with Ipilimumab was tolerable and did not result in dose limiting toxicities (DLTs) but resulted in grade 3 or 4 adverse events in 32% of the patients. The adverse events included hypophysitis, adrenal insufficiency and diarrhea. Studies on T-VEC suggest T-VEC+ipilimumab is more effective than Ipilimumab alone.[108]

Advanced techniques using cDNA-expression cloning and autologous antibodies have allowed for the identification of a wide array of antigens and peptides utilized in manufacturing melanoma vaccines. Further trials are imperative at this point to establish the therapeutic benefit of those vaccines in advanced melanoma as evidence so far is lacking.

Even though treating melanoma using a cancer vaccine is an ingenious approach, several challenges are arising with this strategy. So far, vaccines have been developed based on tumor antigens that are commonly overexpressed and shared across many patients and tumors. One challenge is to develop vaccines that are personalized to each patient, i.e. vaccines based on the antigens the tumor expresses in a particular patient. This approach will add more cost and time but might be more beneficial compared with the general vaccines. In addition, another challenge is to develop vaccines composed of nucleic acids that encode antigens. Developing vaccines based on these nucleic acids might allow more specific immune responses towards the tumor rather than normal tissue. It also allows for vaccinating against several antigens rather than one because of the ability to administer several nucleic acid sequences encoding different antigens. For example, a recent vaccine was developed composed of a nanoparticle containing tetravalent RNA sequences, each encoding a separate antigen, for the treatment of patients with malignant melanoma. The approach allows more efficient targeting of antigen-presenting cells.[118],[119] Despite the ambiguous clinical effectiveness of current melanoma vaccines, they are relatively safe in the management of malignant melanoma.[120]

Cutaneous T-cell lymphoma

Primary cutaneous T-cell lymphomas are defined as clonal proliferation of skin-infiltrating T lymphocytes, which manifest initially in the skin. Cutaneous T-cell lymphomas are generally incurable and therapeutic options are limited, especially in advanced stages. This lead to the development of various treatment strategies including attempts to vaccinate against the malignant tumor.[121]

Neoplastic T cells from cutaneous T-cell lymphomas patients express tumor specific antigens that serve as the targets of an immune response. Thus, one possible vaccination modality is using whole tumor cells or tumor cells fused with dendritic cells to improve delivery to antigen presenting cells.[122] Multiple investigated targets included cancer/testis antigens, anaplastic lymphoma kinase fusion proteins, and mimotopes.[123] Vaccinations of few individuals have shown short partial remissions, but studies have not been published yet and further research is required.


  Vaccines in Immunocompromised Individuals Top


The use of vaccines in immunocompromised individuals is relatively safe and effective. In fact, guidelines have recommended that HIV-infected patients older than 18 years of age receive one dose of the 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with the pneumococcal polysaccharide vaccine (PPV23).[124] Multiple vaccines are currently encouraged and considered safe in the immunocompromised such as the inactivated influenza vaccine in young children,[125] the human papillomavirus vaccine,[126] the live attenuated Oka zoster vaccine,[127] whole-virus cell culture-derived H5N1 influenza vaccines [128] and the heat-treated zoster vaccine.[129]

However, there are a few exceptions that should be noted. First, the varicella vaccine is not recommended in immunocompromised individuals as such individuals may be unable to limit the replication of live attenuated vaccine viruses.[130] Second, the use of replicating smallpox vaccines such as the LC16m8, licensed in Japan, should not be promoted given the limited data on safety and efficacy in immunocompromised individuals.[131] If needed, the World Health Organization advisory group recommends use of a nonreplicating smallpox vaccine comprised modified vaccinia virus Ankara instead.

Currently studies are being designed to examine the potential role of a new vaccine against tuberculosis meningitis,[132]  Brucellosis More Details,[133]Candida albicans infection [134] and Ebola virus [135] in the immunocompromised population.


  Vaccine-Induced Dermatological Adverse Effects Top


Vaccines have been established to be significant contributors in the prevention and treatment of some dermatologic entities. However, just like any modality, their use has been associated with multiple cutaneous adverse effects.

Hepatitis B vaccine

Hepatitis B vaccination has been found to trigger an intense lichenoid reaction in one patient.[136] In another case, lichen planus was induced by anti-hepatitis B vaccination and was successfully treated with prednisone 1 mg/kg/day for 2 weeks.[137] Infantile bullous pemphigoid has been reported in three infants following vaccination for diphtheria, pertussis, tetanus, poliomyelitis, hepatitis B, Haemophilus influenzae B and meningococcus C. However, the etiology remains uncertain. Systemic steroids when given led to resolution of lesions in 2–6 months for two infants, whereas high-potency topical steroids were required for the third infant.[138] [Table 1] includes hepatitis B vaccine as part of the Indian Academy of Paediatrics immunization schedule with possible adverse events, and [Table 2] shows available vaccines, their trade names and their prices.

Smallpox vaccine

A characteristic smooth scar develops following administration of the smallpox vaccine. Based on previous published reports, exaggerated scarring, dermatofibroma and nevus sebaceous (Jadassohn tumor) have been described at the scar site.[139]

Bacillus Calmette–Guérin vaccine

Two case reports describe cutaneous M. bovis infection in two infants with immune disorders following the bacillus Calmette-Guérin vaccination.[140] Another nine case reports published in Japan describe atypical popular tuberculides after bacillus Calmette-Guérin vaccination.[141]


  Conclusion and Future Directions Top


Multiple vaccines are being actively developed for use in dermatologic diseases. Recent advances in the fields of immunotherapy, genetics and molecular technology have allowed for the design of prophylactic and therapeutic vaccines with enormous potential in the field of dermatology. Dermatologists should be aware of the availability and possible use of newer vaccines developed against acne, human papillomavirus, melanoma and other dermatologic disorders. Further studies are necessary to investigate the potential use and benefits of vaccines in the prevention of dermatologic entities such as invasive staphylococcal disease,[142]Streptococcus pyogenes infections [143] and scabies.[144] In the foreseeable future, the development of vaccines will rely more on supplying an RNA molecule instead of an antigen. This method can potentially enable a wide range of cells in our body to form a larger number of proteins and present them to the immune system in a more efficient way.[145] Ongoing active research in vaccine development has opened a new promising era in the field of dermatology. However, many questions remain unanswered, e.g. whether such vaccines offer adequate clinical benefits or even convincing survival advantages.

Limitations

The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. Also, we did not cite any of our authors' own publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
A.F. NicolAndradeRussomanoRodriguesBraz J Med Biol ResKaarthigeyanIndian J Med Paediatr Oncol Hung Ma MonieIndian J DermatolBMJNofal ANofal EYosef ANofal HInt J Dermatol. TalwarGuptaMustafaKarKatochBiologicsThe Leprosy Misison Trust IndiaVaccine for leprosyBrook CEBeauclair RNgwenya OWorden LNdeffo-Mbah MLietman TMParasit Vectors. Xiong CLi QLin MLi XMeng WWu YZeng XJ Oral Pathol Med. Sharma SKKatoch KSarin RBalambal RKumar Jain NSci Rep. Ali MK, Jaacks LM, Kowalski AJ, Siegel KR, Ezzati M. Noncommunicable diseases: Three decades of global data show A mixture of increases and decreases in mortality rates. Health Aff (Millwood) 2015;34:1444-55.  Back to cited text no. 1
[PUBMED]    
2.
World Health Organization. The Expanded Program on Immunization; August 31, 2016. Available from: http://www.searo.who.int/entity/immunization/data/en. [Last accessed on 2017 Jul 15].  Back to cited text no. 2
    
3.
Vashishtha VM, Kumar P. 50 years of immunization in India: Progress and future. Indian Pediatr 2013;50:111-8.  Back to cited text no. 3
    
4.
Ozao-Choy J, Lee DJ, Faries MB. Melanoma vaccines: Mixed past, promising future. Surg Clin North Am 2014;94:1017-30, viii.  Back to cited text no. 4
    
5.
Lakhani S. Early clinical pathologists: Edward Jenner (1749-1823). J Clin Pathol 1992;45:756-8.  Back to cited text no. 5
    
6.
Castle P, Maza M. Prophylactic HPV vaccination: Past, present, and future. Epidemiol Infect 2016;144:449-68.  Back to cited text no. 6
    
7.
Nyitray AG, Iannacone MR. The epidemiology of human papillomaviruses. Curr Probl Dermatol 2014;45:75-91.  Back to cited text no. 7
    
8.
Dany M, Chidiac A, Nassar AH. Human papillomavirus vaccination: Assessing knowledge, attitudes, and intentions of college female students in Lebanon, a developing country. Vaccine 2015;33:1001-7.  Back to cited text no. 8
    
9.
Division of Cancer Prevention and Control, Centers for Disease Control and Prevention. Cervical Cancer Rates by State; July 6, 2016.  Back to cited text no. 9
    
10.
Navalpakam A, Dany M, Hajj Hussein I. Behavioral perceptions of Oakland university female college students towards human papillomavirus vaccination. PLoS One 2016;11:e0155955.  Back to cited text no. 10
    
11.
Petrosky E, Bocchini JA Jr., Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-valent human papillomavirus (HPV) vaccine: Updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015;64:300-4.  Back to cited text no. 11
    
12.
Khatun S, Akram Hussain SM, Chowdhury S, Ferdous J, Hossain F, Begum SR, et al. Safety and immunogenicity profile of human papillomavirus-16/18 AS04 adjuvant cervical cancer vaccine: A randomized controlled trial in healthy adolescent girls of Bangladesh. Jpn J Clin Oncol 2012;42:36-41.  Back to cited text no. 12
    
13.
Nicol AF, Andrade CV, Russomano FB, Rodrigues LL, Oliveira NS, Provance DW Jr., et al. HPV vaccines: A controversial issue? Braz J Med Biol Res 2016;49:e5060.  Back to cited text no. 13
    
14.
Kaarthigeyan K. Cervical cancer in India and HPV vaccination. Indian J Med Paediatr Oncol 2012;33:7-12.  Back to cited text no. 14
  [Full text]  
15.
Yang A, Farmer E, Wu TC, Hung CF. Perspectives for therapeutic HPV vaccine development. J Biomed Sci 2016;23:75.  Back to cited text no. 15
    
16.
Larson HJ, Brocard P, Garnett G. The India HPV-vaccine suspension. Lancet 2010;376:572-3.  Back to cited text no. 16
    
17.
Hawkes S, Kismödi E, Larson H, Buse K. Vaccines to promote and protect sexual health: Policy challenges and opportunities. Vaccine 2014;32:1610-5.  Back to cited text no. 17
    
18.
Graham JE, Mishra A. Global challenges of implementing human papillomavirus vaccines. Int J Equity Health 2011;10:27.  Back to cited text no. 18
    
19.
Maciag PC, Radulovic S, Rothman J. The first clinical use of a live-attenuated listeria monocytogenes vaccine: A Phase I safety study of lm-LLO-E7 in patients with advanced carcinoma of the cervix. Vaccine 2009;27:3975-83.  Back to cited text no. 19
    
20.
Kaufmann AM, Stern PL, Rankin EM, Sommer H, Nuessler V, Schneider A, et al. Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. Clin Cancer Res 2002;8:3676-85.  Back to cited text no. 20
    
21.
Baldwin PJ, van der Burg SH, Boswell CM, Offringa R, Hickling JK, Dobson J, et al. Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia. Clin Cancer Res 2003;9:5205-13.  Back to cited text no. 21
    
22.
Brun JL, Dalstein V, Leveque J, Mathevet P, Raulic P, Baldauf JJ, et al. Regression of high-grade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy. Am J Obstet Gynecol 2011;204:169.e1-8.  Back to cited text no. 22
    
23.
Rosales R, López-Contreras M, Rosales C, Magallanes-Molina JR, Gonzalez-Vergara R, Arroyo-Cazarez JM, et al. Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine. Hum Gene Ther 2014;25:1035-49.  Back to cited text no. 23
    
24.
van Poelgeest MI, Welters MJ, van Esch EM, Stynenbosch LF, Kerpershoek G, van Persijn van Meerten EL, et al. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J Transl Med 2013;11:88.  Back to cited text no. 24
    
25.
Zandberg DP, Rollins S, Goloubeva O, Morales RE, Tan M, Taylor R, et al. Aphase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Cancer Immunol Immunother 2015;64:367-79.  Back to cited text no. 25
    
26.
Coleman HN, Greenfield WW, Stratton SL, Vaughn R, Kieber A, Moerman-Herzog AM, et al. Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination. Cancer Immunol Immunother 2016;65:563-73.  Back to cited text no. 26
    
27.
Van Damme P, Bouillette-Marussig M, Hens A, De Coster I, Depuydt C, Goubier A, et al. GTL001, A therapeutic vaccine for women infected with human papillomavirus 16 or 18 and normal cervical cytology: Results of a phase I clinical trial. Clin Cancer Res 2016;22:3238-48.  Back to cited text no. 27
    
28.
Daayana S, Elkord E, Winters U, Pawlita M, Roden R, Stern PL, et al. Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. Br J Cancer 2010;102:1129-36.  Back to cited text no. 28
    
29.
Smyth LJ, Van Poelgeest MI, Davidson EJ, Kwappenberg KM, Burt D, Sehr P, et al. Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination. Clin Cancer Res 2004;10:2954-61.  Back to cited text no. 29
    
30.
Maldonado L, Teague JE, Morrow MP, Jotova I, Wu TC, Wang C, et al. Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Sci Transl Med 2014;6:221ra13.  Back to cited text no. 30
    
31.
Alvarez RD, Huh WK, Bae S, Lamb LS Jr., Conner MG, Boyer J, et al. Apilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 2016;140:245-52.  Back to cited text no. 31
    
32.
Kim TJ, Jin HT, Hur SY, Yang HG, Seo YB, Hong SR, et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun 2014;5:5317.  Back to cited text no. 32
    
33.
Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, et al. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 2012;4:155ra138.  Back to cited text no. 33
    
34.
Santin AD, Bellone S, Palmieri M, Zanolini A, Ravaggi A, Siegel ER, et al. Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: A phase I escalating-dose trial. J Virol 2008;82:1968-79.  Back to cited text no. 34
    
35.
Ramanathan P, Ganeshrajah S, Raghanvan RK, Singh SS, Thangarajan R. Development and clinical evaluation of dendritic cell vaccines for HPV related cervical cancer – A feasibility study. Asian Pac J Cancer Prev 2014;15:5909-16.  Back to cited text no. 35
    
36.
Hung CF, Ma B, Monie A, Tsen SW, Wu TC. Therapeutic human papillomavirus vaccines: Current clinical trials and future directions. Expert Opin Biol Ther 2008;8:421-39.  Back to cited text no. 36
    
37.
Xu F, Sternberg M, Gottlieb S, Berman S, Markowitz L, Forhan S, et al. Seroprevalence of herpes simplex virus type 2 among persons aged 14-49 years-United States, 2005-2008. Morb Mortal Wkly Rep 2010;59:456-9.  Back to cited text no. 37
    
38.
Zhu XP, Muhammad ZS, Wang JG, Lin W, Guo SK, Zhang W, et al. HSV-2 vaccine: Current status and insight into factors for developing an efficient vaccine. Viruses 2014;6:371-90.  Back to cited text no. 38
    
39.
Madhivanan P, Krupp K, Chandrasekaran V, Karat C, Arun A, Klausner JD, et al. The epidemiology of herpes simplex virus type-2 infection among married women in Mysore, India. Sex Transm Dis 2007;34:935-7.  Back to cited text no. 39
    
40.
Cowan FM, French RS, Mayaud P, Gopal R, Robinson NJ, de Oliveira SA, et al. Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka. Sex Transm Infect 2003;79:286-90.  Back to cited text no. 40
    
41.
Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics. J Acquir Immune Defic Syndr 2004;35:435-45.  Back to cited text no. 41
    
42.
Vaccines Licensed for the Use in the United States. U.S. Food and Drug Administration. Available from: https://www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts. [Last accessed on 2017 Jul 12].  Back to cited text no. 42
    
43.
Belshe RB, Leone P, Bernstein D, Wald A, Levin M, Stapleton J, et al. Efficacy results of a trial of a herpes simplex vaccine herpevac trial for women. N Engl J Med 2012;366:34-43.  Back to cited text no. 43
    
44.
Wald A, Bernstein D, Fife K, Lee P, Tyring S, Van Wagoner N. Novel Therapeutic Vaccine for Genital Herpes Reduces Genital HSV-2 Shedding. In: 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2013.  Back to cited text no. 44
    
45.
Long D, Skoberne M, Gierahn TM, Larson S, Price JA, Clemens V, et al. Identification of novel virus-specific antigens by CD4+ and CD8+ T cells from asymptomatic HSV-2 seropositive and seronegative donors. Virology 2014;464-465:296-311.  Back to cited text no. 45
    
46.
Skoberne M, Cardin R, Lee A, Kazimirova A, Zielinski V, Garvie D, et al. An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in guinea pigs. J Virol 2013;87:3930-42.  Back to cited text no. 46
    
47.
Wald A, Koelle DM, Fife K, Warren T, Leclair K, Chicz RM, et al. Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons. Vaccine 2011;29:8520-9.  Back to cited text no. 47
    
48.
Johnston C, Gottlieb SL, Wald A. Status of vaccine research and development of vaccines for herpes simplex virus. Vaccine 2016;34:2948-52.  Back to cited text no. 48
    
49.
Petro C, González PA, Cheshenko N, Jandl T, Khajoueinejad N, Bénard A, et al. Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease. Elife 2015;4 doi: 10.7554/eLife. 06054.  Back to cited text no. 49
    
50.
Prichard MN, Kaiwar R, Jackman WT, Quenelle DC, Collins DJ, Kern ER, et al. Evaluation of AD472, a live attenuated recombinant herpes simplex virus type 2 vaccine in guinea pigs. Vaccine 2005;23:5424-31.  Back to cited text no. 50
    
51.
Zhang P, Xie L, Balliet JW, Casimiro D, Yao F. Herpes simplex virus 2 (HSV-2) glycoprotein D-expressing nonreplicating dominant-negative HSV-2 virus vaccine is superior to a gD2 subunit vaccine against HSV-2 genital infection in guinea pigs. PLoS One 2014;9:1-9.   Back to cited text no. 51
    
52.
Morello CS, Kraynyak KA, Levinson MS, Chen Z, Lee KF, Spector DH, et al. Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge. Vaccine 2012;30:6541-50.  Back to cited text no. 52
    
53.
Chiuppesi F, Vannucci L, De Luca A, Lai M, Matteoli B, Freer G, et al. Alentiviral vector-based, herpes simplex virus 1 (HSV-1) glycoprotein B vaccine affords cross-protection against HSV-1 and HSV-2 genital infections. J Virol 2012;86:6563-74.  Back to cited text no. 53
    
54.
Cortesi R, Ravani L, Rinaldi F, Marconi P, Drechsler M, Manservigi M, et al. Intranasal immunization in mice with non-ionic surfactants vesicles containing HSV immunogens: A preliminary study as possible vaccine against genital herpes. Int J Pharm 2013;440:229-37.  Back to cited text no. 54
    
55.
Seward J, Marin M. World Health Organization SAGE Meeting. Varicella Disease Burden and Varicella Vaccines; April, 2014. Available from: http://www.who.int/immunization/sage/meetings/2014/april/2_SAGE_April_VZV_Seward_Varicella.pdf?ua=1&ua=1.. [Last accessed on 2018 Jan 30].  Back to cited text no. 55
    
56.
Katakam BK, Kiran G, Kumar U. A prospective study of herpes zoster in children. Indian J Dermatol 2016;61:534-9.  Back to cited text no. 56
[PUBMED]  [Full text]  
57.
World Health Organization. Background Paper on Varicella Vaccine; SAGE Working Group on Varicella and Herpes Zoster Vaccines; April, 2014. Available from: http://www.who.int/immunization/sage/meetings/2014/april/1_SAGE_varicella_background_paper_FINAL.pdf., accessed January 30, 2018  Back to cited text no. 57
    
58.
Wutzler P, Bonanni P, Burgess M, Gershon A, Sáfadi MA, Casabona G, et al. Varicella vaccination – The global experience. Expert Rev Vaccines 2017;16:833-43.  Back to cited text no. 58
    
59.
Tafuri S, Guerra R, Cappelli MG, Martinelli D, Prato R, Germinario C, et al. Determinants of varicella breakthrough: Results of a 2012 case control study. Hum Vaccin Immunother 2014;10:667-70.  Back to cited text no. 59
    
60.
Centers for Disease Control and Prevention (CDC). Elimination of rubella and congenital rubella syndrome – United States, 1969-2004. MMWR Morb Mortal Wkly Rep 2005;54:279-82.  Back to cited text no. 60
    
61.
Singh M, Devi R, Chauhan A. India to introduce rubella and rotavirus vaccines and inactivated polio vaccine. Br Med J 2014;349:g4844.  Back to cited text no. 61
    
62.
Chakravarti A, Jain M. Rubella prevalence and its transmission in children. Indian J Pathol Microbiol 2006;49:54-6.  Back to cited text no. 62
[PUBMED]  [Full text]  
63.
Klein NP, Fireman B, Yih WK, Lewis E, Kulldorff M, Ray P, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics 2010;126:e1-8.  Back to cited text no. 63
    
64.
Scuffham PA, Lowin AV, Burgess MA. The cost-effectiveness of varicella vaccine programs for Australia. Vaccine 1999;18:407-15.  Back to cited text no. 64
    
65.
Cook SJ, Flaherty DK. Review of the persistence of herpes zoster vaccine efficacy in clinical trials. Clin Ther 2015;37:2388-97.  Back to cited text no. 65
    
66.
Nofal A, Nofal E, Yosef A, Nofal H. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: A promising approach. Int J Dermatol 2015;54:667-71.  Back to cited text no. 66
    
67.
Saini P, Mittal A, Gupta LK, Khare AK, Mehta S. Intralesional mumps, measles and rubella vaccine in the treatment of cutaneous warts. Indian J Dermatol Venereol Leprol 2016;82:343-5.  Back to cited text no. 67
[PUBMED]  [Full text]  
68.
Na CH, Kim DJ, Kim MS, Kim JK, Shin BS. Successful treatment of molluscum contagiosum with intralesional immunotherapy by measles, mumps, and rubella vaccine: A report of two cases. Dermatol Ther 2014;27:373-6.  Back to cited text no. 68
    
69.
National AIDS Control Organization NACO, India Annual Report 2015-16; 2015. Available from: http://www.naco.gov.in/sites/default/files/Annual%20Report%202015-16_NACO.pdf. [Last accessed on 2018 Jan 30].  Back to cited text no. 69
    
70.
World Health Organization, Global Health Observatory (GHO) Data: HIV/AIDS. Available from: http://www.who.int/gho/hiv/en.[Last accessed on 2018 Jan 30].  Back to cited text no. 70
    
71.
Trivedi S, Jackson RJ, Ranasinghe C. Different HIV pox viral vector-based vaccines and adjuvants can induce unique antigen presenting cells that modulate CD8 T cell avidity. Virology 2014;468-470:479-89.  Back to cited text no. 71
    
72.
Teigler JE, Phogat S, Franchini G, Hirsch VM, Michael NL, Barouch DH, et al. The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vaccinia virus-based vectors MVA and NYVAC in rhesus monkeys. J Virol 2014;88:1809-14.  Back to cited text no. 72
    
73.
Gómez CE, Perdiguero B, Garcia-Arriaza J, Esteban M. Poxvirus vectors as HIV/AIDS vaccines in humans. Hum Vaccin Immunother 2012;8:1192-207.  Back to cited text no. 73
    
74.
Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 2006;194:1661-71.  Back to cited text no. 74
    
75.
Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, del Rio C, et al. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step study). J Infect Dis 2012;206:258-66.  Back to cited text no. 75
    
76.
Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, et al. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: A double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis 2011;11:507-15.  Back to cited text no. 76
    
77.
Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 2013;369:2083-92.  Back to cited text no. 77
    
78.
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209-20.  Back to cited text no. 78
    
79.
Shin SY. Recent update in HIV vaccine development. Clin Exp Vaccine Res 2016;5:6-11.  Back to cited text no. 79
    
80.
Cafaro A, Tripiciano A, Sgadari C, Bellino S, Picconi O, Longo O, et al. Development of a novel AIDS vaccine: The HIV-1 transactivator of transcription protein vaccine. Expert Opin Biol Ther 2015;15 Suppl 1:S13-29.  Back to cited text no. 80
    
81.
Routy JP, Nicolette C. Arcelis AGS-004 dendritic cell-based immunotherapy for HIV infection. Immunotherapy 2010;2:467-76.  Back to cited text no. 81
    
82.
Simonart T. Immunotherapy for acne vulgaris: Current status and future directions. Am J Clin Dermatol 2013;14:429-35.  Back to cited text no. 82
    
83.
National Leprosy Eradication Program. NLEP Annual Report 2015-2016. Ministry of Health and Family Welfare, Government of India. Available from: http://www.nlep.nic.in/pdf/revised%20annual%20report%2031st%20March%202015-16.pdf. [Last accessed on 2017 Jul 13].  Back to cited text no. 83
    
84.
Leprosy: High Power Committee to Evaluate the Performance of ICMR, 2012-13, Disease Specific Documents for XII Plan, Annexure XVI, Indian Council of Medical Research, New Delhi; 2014. Available from: http://www.icmr.nic.in/Publications/hpc/PDF/Annexure%2016.pdf. [Last accessed on 2017 Jul 13].  Back to cited text no. 84
    
85.
Gormus BJ, Meyers WM. Under-explored experimental topics related to integral mycobacterial vaccines for leprosy. Expert Rev Vaccines 2003;2:791-804.  Back to cited text no. 85
    
86.
Rana A, Thakur S, Bhardwaj N, Kumar D, Akhter Y. Excavating the surface-associated and secretory proteome of mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes. Pathog Dis 2016;74. pii: ftw110.  Back to cited text no. 86
    
87.
Sharma P, Mukherjee R, Talwar GP, Sarathchandra KG, Walia R, Parida SK, et al. Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: Clinical field trials with a follow up of 8-10 years. Lepr Rev 2005;76:127-43.  Back to cited text no. 87
    
88.
Kamal R, Pathak V, Kumari A, Natrajan M, Katoch K, Kar HK, et al. Addition of Mycobacterium indicus pranii vaccine as an immunotherapeutic to standard chemotherapy in borderline leprosy: A double-blind study to assess clinical improvement (preliminary report). Br J Dermatol 2017;176:1388-9.  Back to cited text no. 88
    
89.
Talwar GP, Gupta JC, Mustafa AS, Kar HK, Katoch K, Parida SK, et al. Development of a potent invigorator of immune responses endowed with both preventive and therapeutic properties. Biologics 2017;11:55-63.  Back to cited text no. 89
    
90.
Talwar G. National JALMA Institute for Leprosy and Other Mycobacterial Diseases. The Leprosy Misison Trust India, Vaccine for Leprosy; September, 2016. Available from: http://www.tlmindia.org/a-promising-vaccine-against-leprosy-govt-of-india-plans-large-scale-field-testing/. [Last accessed on 2017 Jul 13].  Back to cited text no. 90
    
91.
Brook CE, Beauclair R, Ngwenya O, Worden L, Ndeffo-Mbah M, Lietman TM, et al. Spatial heterogeneity in projected leprosy trends in India. Parasit Vectors 2015;8:542.  Back to cited text no. 91
    
92.
Talwar GP. An immunotherapeutic vaccine for multibacillary leprosy. Int Rev Immunol 1999;18:229-49.  Back to cited text no. 92
    
93.
Nery JA, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira Sde S, Sales AM, et al. Understanding the type 1 reactional state for early diagnosis and treatment: A way to avoid disability in leprosy. An Bras Dermatol 2013;88:787-92.  Back to cited text no. 93
    
94.
Steere AC, Sikand VK, Meurice F, Parenti DL, Fikrig E, Schoen RT, et al. Vaccination against lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme disease vaccine study group. N Engl J Med 1998;339:209-15.  Back to cited text no. 94
    
95.
Wressnigg N, Barrett PN, Pöllabauer EM, O'Rourke M, Portsmouth D, Schwendinger MG, et al. Anovel multivalent OspA vaccine against Lyme borreliosis is safe and immunogenic in an adult population previously infected with Borrelia burgdorferi sensu lato. Clin Vaccine Immunol 2014;21:1490-9.  Back to cited text no. 95
    
96.
von Stebut E. Cutaneous leishmania infection: Progress in pathogenesis research and experimental therapy. Exp Dermatol 2007;16:340-6.  Back to cited text no. 96
    
97.
Flohé SB, Bauer C, Flohé S, Moll H. Antigen-pulsed epidermal langerhans cells protect susceptible mice from infection with the intracellular parasite leishmania major. Eur J Immunol 1998;28:3800-11.  Back to cited text no. 97
    
98.
Berberich C, Ramírez-Pineda JR, Hambrecht C, Alber G, Skeiky YA, Moll H, et al. Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens. J Immunol 2003;170:3171-9.  Back to cited text no. 98
    
99.
Wu W, Weigand L, Belkaid Y, Mendez S. Immunomodulatory effects associated with a live vaccine against Leishmania major containing CpG oligodeoxynucleotides. Eur J Immunol 2006;36:3238-47.  Back to cited text no. 99
    
100.
Vélez ID, Gilchrist K, Arbelaez MP, Rojas CA, Puerta JA, Antunes CM, et al. Failure of a killed Leishmania amazonensis vaccine against American cutaneous leishmaniasis in Colombia. Trans R Soc Trop Med Hyg 2005;99:593-8.  Back to cited text no. 100
    
101.
Gillespie PM, Beaumier CM, Strych U, Hayward T, Hotez PJ, Bottazzi ME, et al. Status of vaccine research and development of vaccines for leishmaniasis. Vaccine 2016;34:2992-5.  Back to cited text no. 101
    
102.
Sharquie KE, Al-Rawi JR, Al-Nuaimy AA, Radhy SH. Bacille calmette-guerin immunotherapy of viral warts. Saudi Med J 2008;29:589-93.  Back to cited text no. 102
    
103.
Alsharif S, Alzanbagi H, Melebari D, Firaq N. Intralesional immunotherapy with bacille calmette-guerin (BCG) vaccine for the treatment of warts: Case report and systematic review. Int J Biol Med Res 2017:5820-6.  Back to cited text no. 103
    
104.
Xiong C, Li Q, Lin M, Li X, Meng W, Wu Y, et al. The efficacy of topical intralesional BCG-PSN injection in the treatment of erosive oral lichen planus: A randomized controlled trial. J Oral Pathol Med 2009;38:551-8.  Back to cited text no. 104
    
105.
Miller AJ, Mihm MC Jr. Melanoma. N Engl J Med 2006;355:51-65.  Back to cited text no. 105
    
106.
Macdonald JB, Dueck AC, Gray RJ, Wasif N, Swanson DL, Sekulic A, et al. Malignant melanoma in the elderly: Different regional disease and poorer prognosis. J Cancer 2011;2:538-43.  Back to cited text no. 106
    
107.
Dany M, Nganga R, Chidiac A, Hanna E, Matar S, Elston D, et al. Advances in immunotherapy for melanoma management. Hum Vaccin Immunother 2016;12:2501-11.  Back to cited text no. 107
    
108.
Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. Gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 2011;364:2119-27.  Back to cited text no. 108
    
109.
Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: Clinical and immunologic findings. J Clin Oncol 2002;20:4169-80.  Back to cited text no. 109
    
110.
Eggermont AM, Maio M, Robert C. Immune checkpoint inhibitors in melanoma provide the cornerstones for curative therapies. Semin Oncol 2015;42:429-35.  Back to cited text no. 110
    
111.
Eggermont AM, Suciu S, Rutkowski P, Marsden J, Santinami M, Corrie P, et al. Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor>1.5 mm in patients with stage II melanoma: Results of the EORTC 18961 randomized phase III trial. J Clin Oncol 2013;31:3831-7.  Back to cited text no. 111
    
112.
Kawakami Y, Robbins PF, Wang RF, Parkhurst M, Kang X, Rosenberg SA, et al. The use of melanosomal proteins in the immunotherapy of melanoma. J Immunother 1998;21:237-46.  Back to cited text no. 112
    
113.
H. M. Zarour and J. M. Kirkwood, “Melanoma vaccines: early progress and future promises,” Seminars in Cutaneous Medicine and Surgery, vol. 22, no. 1, pp. 68–75, 2003.  Back to cited text no. 113
    
114.
Lesterhuis WJ, Schreibelt G, Scharenborg NM, Brouwer HM, Gerritsen MJ, Croockewit S, et al. Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used. Cancer Immunol Immunother 2011;60:249-60.  Back to cited text no. 114
    
115.
Greene JM, Schneble EJ, Jackson DO, Hale DF, Vreeland TJ, Flores M, et al. Aphase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2. Cancer Immunol Immunother 2016;65:383-92.  Back to cited text no. 115
    
116.
OPTiM: A Randomized Phase III Trial of Talimogene Laherparepvec (T-VEC) Versus Subcutaneous (SC) Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) for the Treatment (tx) of Unresected Stage IIIB/C and IV Melanoma. ASCO Annual Meeting Proceedings; 2013.  Back to cited text no. 116
    
117.
Jabulowsky RA, Loquai C, Diken M, Kranz LM, Haas H, Attig S, et al. Abstract B041: A novel nanoparticular formulated tetravalent RNA cancer vaccine for treatment of patients with malignant melanoma. Cancer Immunol Res 2016;4 1 Suppl:B041.  Back to cited text no. 117
    
118.
Butterfield LH. Lessons learned from cancer vaccine trials and target antigen choice. Cancer Immunol Immunother 2016;65:805-12.  Back to cited text no. 118
    
119.
Kuhn CA, Hanke CW. Current status of melanoma vaccines. Dermatol Surg 1997;23:649-54.  Back to cited text no. 119
    
120.
Wang L, Ni X, Covington KR, Xi L, Wheeler DA, Duvic M. Molecular pathogenesis of an advanced cutaneous T-cell lymphoma. Cancer Res 2016;76 14 Suppl: 124.  Back to cited text no. 120
    
121.
Seo N, Furukawa F, Tokura Y, Takigawa M. Vaccine therapy for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 2003;17:1467-74.  Back to cited text no. 121
    
122.
Muche JM, Sterry W. Vaccination therapy for cutaneous T-cell lymphoma. Clin Exp Dermatol 2002;27:602-7.  Back to cited text no. 122
    
123.
Lee KY, Tsai MS, Kuo KC, Tsai JC, Sun HY, Cheng AC, et al. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy. Hum Vaccin Immunother 2014;10:3700-10.  Back to cited text no. 123
    
124.
Isaacs D. Inactivated influenza vaccine highly effective in young and immunocompromised children. J Paediatr Child Health 2016;52:784.  Back to cited text no. 124
    
125.
MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, et al. Immunogenicity and persistence of immunity of a quadrivalent human papillomavirus (HPV) vaccine in immunocompromised children. Vaccine 2016;34:4343-50.  Back to cited text no. 125
    
126.
Oxman MN, Schmader KE. Editorial commentary: Zoster vaccine in immunocompromised patients: Time to reconsider current recommendations. Clin Infect Dis 2014;59:920-2.  Back to cited text no. 126
    
127.
van der Velden MV, Fritz R, Pöllabauer EM, Portsmouth D, Howard MK, Kreil TR, et al. Safety and immunogenicity of a vero cell culture-derived whole-virus influenza A (H5N1) vaccine in a pediatric population. J Infect Dis 2014;209:12-23.  Back to cited text no. 127
    
128.
Mullane KM, Winston DJ, Wertheim MS, Betts RF, Poretz DM, Camacho LH, et al. Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults. J Infect Dis 2013;208:1375-85.  Back to cited text no. 128
    
129.
Sartori AM. A review of the varicella vaccine in immunocompromised individuals. Int J Infect Dis 2004;8:259-70.  Back to cited text no. 129
    
130.
Danon YL, Sutter G. Use of the LC16m8 smallpox vaccine in immunocompromised individuals is still too risky. Clin Vaccine Immunol 2015;22:604.  Back to cited text no. 130
    
131.
Rees J. New vaccine against TB meningitis potentially appropriate for the immunocompromised. Expert Rev Anti Infect Ther 2013;11:765.  Back to cited text no. 131
    
132.
Arenas-Gamboa AM, Rice-Ficht AC, Fan Y, Kahl-McDonagh MM, Ficht TA. Extended safety and efficacy studies of the attenuated Brucella vaccine candidates 16 M (Delta) vjbR and S19(Delta) vjbR in the immunocompromised IRF-1-/- mouse model. Clin Vaccine Immunol 2012;19:249-60.  Back to cited text no. 132
    
133.
Lipinski T, Wu X, Sadowska J, Kreiter E, Yasui Y, Cheriaparambil S, et al. Aβ-mannan trisaccharide conjugate vaccine aids clearance of candida albicans in immunocompromised rabbits. Vaccine 2012;30:6263-9.  Back to cited text no. 133
    
134.
Geisbert TW, Daddario-Dicaprio KM, Lewis MG, Geisbert JB, Grolla A, Leung A, et al. Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathog 2008;4:e1000225.  Back to cited text no. 134
    
135.
Saywell CA, Wittal RA, Kossard S. Lichenoid reaction to hepatitis B vaccination. Australas J Dermatol 1997;38:152-4.  Back to cited text no. 135
    
136.
Calista D, Morri M. Lichen planus induced by hepatitis B vaccination: A new case and review of the literature. Int J Dermatol 2004;43:562-4.  Back to cited text no. 136
    
137.
Schwieger-Briel A, Moellmann C, Mattulat B, Schauer F, Kiritsi D, Schmidt E, et al. Bullous pemphigoid in infants: Characteristics, diagnosis and treatment. Orphanet J Rare Dis 2014;9:185.  Back to cited text no. 137
    
138.
Waibel KH, Walsh DS. Smallpox vaccination site complications. Int J Dermatol 2006;45:684-8.  Back to cited text no. 138
    
139.
Antaya RJ, Gardner ES, Bettencourt MS, Daines M, Denise Y, Uthaisangsook S, et al. Cutaneous complications of BCG vaccination in infants with immune disorders: Two cases and a review of the literature. Pediatr Dermatol 2001;18:205-9.  Back to cited text no. 139
    
140.
Muto J, Kuroda K, Tajima S. Papular tuberculides post-BCG vaccination: Case report and review of the literature in Japan. Clin Exp Dermatol 2006;31:611-2.  Back to cited text no. 140
    
141.
Shinefield HR. Use of a conjugate polysaccharide vaccine in the prevention of invasive staphylococcal disease: Is an additional vaccine needed or possible? Vaccine 2006;24 Suppl 2:S2-65-9.  Back to cited text no. 141
    
142.
Areschoug T, Carlsson F, Stålhammar-Carlemalm M, Lindahl G. Host-pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development. Vaccine 2004;22 Suppl 1:S9-14.  Back to cited text no. 142
    
143.
Hengge UR, Currie BJ, Jäger G, Lupi O, Schwartz RA. Scabies: A ubiquitous neglected skin disease. Lancet Infect Dis 2006;6:769-79.  Back to cited text no. 143
    
144.
Grabbe S, Haas H, Diken M, Kranz LM, Langguth P, Sahin U, et al. Translating nanoparticulate-personalized cancer vaccines into clinical applications: Case study with RNA-lipoplexes for the treatment of melanoma. Nanomedicine (Lond) 2016;11:2723-34.  Back to cited text no. 144
    
145.
Advisory Committee on Immunization Practices, U.S. Department of Health and Human Services. Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger. Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf. [Last accessed on 2017 Jul 12].  Back to cited text no. 145
    
146.
World Health Organization. The Expanded Program on Immunization; August 31, 2016. Available from: http://www.searo.who.int/entity/immunization/data/india.pdf?ua=1. [Last accessed on 2017 Jul 12].  Back to cited text no. 146
    
147.
Talwar G, Singh P, Atrey N, Gupta J. Making of a highly useful multipurpose vaccine. J Transl Sci 2016; doi: 10.15761/JTS.1000117  Back to cited text no. 147
    
148.
Sharma SK, Katoch K, Sarin R, Balambal R, Kumar Jain N, Patel N, et al. Efficacy and safety of Mycobacterium Indicus pranii as an adjunct therapy in category II pulmonary tuberculosis in a randomized trial. Sci Rep 2017;7:3354.  Back to cited text no. 148
    
149.
Indian Academy of Pediatrics, IAP Immunization Timetable; 2016. Available from: http://www.acvip.org/files/Table%20I-IAP%20Immunization%20Schedule%202016-Final.pdf. [Last accessed on 2017 Jul 14].  Back to cited text no. 149
    
150.
MedIndia Network for Health, Drug “Measles, Mumps, and Rubella (mmr) Vaccine” Price List. Available from: http://www.medindia.net/drug-price/measles-mumps-and-rubella-mmr-vaccine.htm. [Last accessed on 2017 Jul 13; Last updated on 2017 Feb 02].  Back to cited text no. 150
    
151.
Kshirsager G. Detailed Cost of Vaccination/Immunization in India (Birth to 10 years of age); February, 2017. Available from: https://www.raisingtwinsblog.files.wordpress.com/2017/02/detailed-cost-of-vaccination-in-india-2017-protected1.pdf. [Last accessed on 2017 Jul 13].  Back to cited text no. 151
    
152.
Available from: https://www.medplusmart.com/product. [Last accessed on 2017 Jul 13].  Back to cited text no. 152
    
153.
Market Assessment of New Vaccines. Immunization Technical Support Unit, Public Health Foundation of India; September, 2015. p. 1-136. Available from: http://www.sathguru.com/Publication/download/Market-Assessment-of-New-Vaccines.pdf. [Last accessed on 2017 Jul 15].  Back to cited text no. 153
    
154.
National Leprosy Eradication Program, Directorate General of Health Services, Ministry of Health and Family Welfare, India. Available from: http://www.nlep.nic.in/about.html. [Last accessed on 2017 Jul 13].  Back to cited text no. 154
    
155.
World Health Organization. WHO Vaccine Reaction Rates Information Sheets, the Global Vaccine Safety Initiative. Available from: http://www.who.int/vaccine_safety/initiative/tools/vaccinfosheets/en/. [Last accessed on 2017 Jul 13].  Back to cited text no. 155
    
156.
Available from: http://www.drugsupdate.com/brand/showavailablebrands/559. [Last accessed on 2017 Jul 14].  Back to cited text no. 156
    
157.
Veselenak RL, Shlapobersky M, Pyles RB, Wei Q, Sullivan SM, Bourne N, et al. Avaxfectin ®-adjuvanted HSV-2 plasmid DNA vaccine is effective for prophylactic and therapeutic use in the guinea pig model of genital herpes. Vaccine 2012;30:7046-51.  Back to cited text no. 157
    
158.
Bernard MC, Barban V, Pradezynski F, de Montfort A, Ryall R, Caillet C, et al. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs. PLoS One 2015;10:e0121518.  Back to cited text no. 158
    
159.
Awasthi S, Huang J, Shaw C, Friedman HM. Blocking herpes simplex virus2 glycoprotein E immune evasion as an approach to enhance efficacy of a trivalent subunit antigen vaccine for genital herpes. J Virol 2014;88:8421-32.  Back to cited text no. 159
    
160.
Halford WP, Püschel R, Gershburg E, Wilber A, Gershburg S, Rakowski B, et al. Alive-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine. PLoS One 2011;6:e17748.  Back to cited text no. 160
    
161.
Luo C, Goshima F, Kamakura M, Mutoh Y, Iwata S, Kimura H, et al. Immunization with a highly attenuated replication-competent herpes simplex virus type 1 mutant, HF10, protects mice from genital disease caused by herpes simplex virus type 2. Front Microbiol 2012;3:158.  Back to cited text no. 161
    
162.
Churchyard GJ, Morgan C, Adams E, Hural J, Graham BS, Moodie Z, et al. Aphase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PLoS One 2011;6:e21225.  Back to cited text no. 162
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
Print this article  Email this article

    

Online since 15th March '04
Published by Wolters Kluwer - Medknow