Vaccines in Dermatology –

Where do we stand
Dr. Aparajita Ghosh
Viral
infections

Bacterial
infections
Parasitic infections

Cutaneous malignancies
Vaccines for Viral Infections
o Human papilloma virus
o Herpes simplex virus
o Varicella‑zoster virus
o measles‑mumps‑rubella
o SARS –COV-2
o Human Immunodeficiency Virus
Vaccines for Bacterial or Parasitic Infections

o Mycobacterium leprae

o Cutaneous leishmaniasis

o Cutaneous tuberculosis
Vaccines for Treatment of Skin Malignancies
➢Melanoma
➢Cutaneous T‑cell lymphoma
Vaccines for HPV
• Bivalent /2vHPV (cervarix) – HPV 16,18
• Quadrivalent /4vHPV (Gardasil) – HPV 6,11,16,18
• 9 – valent/9vHPV (Gardasil-9) – HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 –
LAUNCHED Sept 2021 in India

• Can prevent most cases of cervical cancer if the vaccine is given

before girls or women are exposed to the virus.
• Can also prevent some cases of vaginal and vulvar cancer
• Can prevent genital warts, anal cancers, and oral cancers in women
and men.
Vaccines for HPV – When to give?
CDC’s Advisory Committee on Immunization Practices (ACIP)
recommendations
• All 11- and 12-year-olds receive two doses of HPV vaccine at least six months
apart. Vaccination may be given at the minimum age of 9 years. Two-dose
schedule is effective for children under 15.

• Teens and young adults who begin the vaccine series later, at ages 15 through 26,
should receive three doses of the vaccine.

• Catch-up HPV vaccinations for all people till age 26 who aren't adequately
vaccinated especially high risk groups MSMs and HIV positive individuals.

• No Pap smear required before vaccination

Vaccines for HPV
• Do you offer HPV vaccine to patients who are already sexually active?
• Yes, because it can protect from other strains that they don't yet
have. However, none of the vaccines can treat an existing HPV
infection.
Does HPV vaccination have any therapeutic
use?
• Bossart S, et al. Nonavalent
human papillomavirus
vaccination as alternative
treatment for genital warts. • Kost Y, et al. Vaccination
Dermatol ther. 2020 against human papillomavirus
• Kost Y, et al. Clearance of is not associated with
recalcitrant warts in a pediatric resolution of verruca vulgaris
patient following administration in immunocompetent 9-to
of the nine‐valent human 21-year olds. JAAD 2021.
papillomavirus vaccine. Pediatric • Husein-ElAhmed H. Could the
Dermatol. 2020 human papillomavirus
• Daniel BS. Complete resolution vaccine prevent recurrence of
of chronic multiple verruca ano-genital warts?: a
vulgaris treated with systematic review and meta-
quadrivalent human analysis. Int journal of STD &
papillomavirus vaccine. JAMA AIDS. 2020
dermatology. 2013
Vaccine HPV vaccine candidate and Vaccine platform Development status
category
Live vector Lm‑LLo‑E7 prfA (the transcriptional activator of Phase I clinical trials
based (bacterial) virulence genes)
‑
Live vector TA‑HPV Recombinant vaccinia virus (encodes Phase II clinical trials
based (viral) oncoproteins E6 and E7 of both HPV 16 and
HPV18

TG4001 Recombinant modified vaccinia

Ankara‑expressing HPV‑16 E6, E7, and IL‑2 Phase I clinical trials

MVA E2 Recombinant modified vaccinia

Ankara encoding E2 from bovine
papillomavirus
Phase III clinical trials
Vaccine HPV vaccine candidate and Vaccine platform Development
category status

Protein/peptide HPV 16‑SLP vaccine [ Combination of nine HPV‑16 E6 and four Phase II
based HPV‑16 E7 synthetic peptides adjuvanated with Freund’s adjuvant
(solution emulsified in mineral oil)]

GL‑0810 HPV‑16 immunomodulatory peptide with adjuvant Phase I

montanide and granulocyte macrophage colony stimulating factor

Pepcan + candin HPV16 E6 peptides combined with Candida skin Phase I

testing reagent candin

GTL001 Recombinant HPV16 and HPV18 E7 proteins fused to Phase I

inactive B. pertussis adenylate CyaA expressed in E. coli
Phase I
TA‑CIN HPV16 E6/E7/L2 fusion protein

TA‑CIN+TA‑HPV HPV16 E6/E7/L2 fusion protein and vaccinia Phase II

virus with HPV16/18 E6/E7
Vaccine HPV vaccine candidate and Vaccine platform Developme
category nt status

Nucleic pNGVL4a‑sig/E7 (detox)/ HSP70 + TA‑HPV [Plasmid encoding mutated form Phase I
acid‑based of HPV16‑E7 linked to sig and heat shock protein HSP70 and vaccinia virus
with HPV16/18 E6/E7]

pNGVL4a‑CRT/E7 (detox)[Plasmid encoding mutated form of HPV16‑E7 Phase I

linked to calreticulin]

VGX‑3100 [Mixture of two plasmids encoding optimized consensus of E6 Phase I & II

and E7 antigen of HPV 16 and 18]

Cell based DC + KLH [DC pulsed with HPV‑16 and HPV‑18 E7 and KLH] Phase I

DC [DC pulsed with HPV + tumor lysate] Phase I

Vaccines for VZV
• Vaccine for varicella (Varilrix /varivax)
• Vaccine for zoster
Varicella vaccine vs Zoster vaccine
• The Zoster vaccine (zostavax) is a lyophilized preparation of the
Oka/Merck strain and differs from Varicella vaccine in potency. The
minimum potency of zoster vaccine (4.29 log10 PFU/dose) is about 14-
fold greater than varicella vaccine.
Shingles / zoster vaccine – When to give?
CDC’s Advisory Committee on Immunization Practices (ACIP)
recommendations

• Single dose of Zostavax® (zoster vaccine live) for people 60 years old
or older
, irrespective of : History of varicella or herpes zoster. C/I in
immunocompromised individuals due to drug or disease.
• DISCONTINUED IN US SINCE NOV. 2020 due to potential to cause
necrotising retinitis
• Available in India since 2016.
Shingles / zoster vaccine
CDC recommends Shingrix (recombinant zoster vaccine, or RZV) for the
prevention of herpes zoster (shingles) and related complications. CDC
recommends two doses of Shingrix separated by 2 to 6 months for
• immunocompetent adults aged 50 years and older
• Vaccination of Immunocompromised Adults 19 Years and Older who
are or will be immunodeficient or immunosuppressed because of
disease or therapy
Currently unavailable in India
 MMR vaccine (Mumps measles rubella)
• Salman S, et al. Intralesional immunotherapy for the treatment of warts: A network meta-analysis. JAAD 2019
PPD (OR 39.56), MMR (OR 17.46) and interferon β (OR 15.55) had the highest efficacy in terms of
complete recovery at the primary site compared with placebo. Regarding complete recovery at the
distant site, autoinoculation (OR 79.95), PPD (OR 42.95), and MMR (OR 15.39) were all statistically
superior to placebo. According to the P-score, MMR was more effective than other modalities in
reducing the recurrence rate at the same site.

• Vania R, et al. Intralesional measles–mumps–rubella is associated with a higher complete response in cutaneous warts:
a systematic review and meta-analysis of randomized controlled trial including GRADE qualification. Journal of
Dermatological Treatment. 2021
In our meta-analysis, we calculated the complete response of wart with intralesional MMR is
77%, which is similarly as effective as other immunotherapy agents
• Nacianceno PA, et alo. Intralesional Measles, Mumps, and Rubella Vaccine for Cutaneous Warts: A Systematic Review
and Meta-analysis. Acta Medica Philippina. 2019.
• Intralesional MMR vaccine and a highly significant difference in completely clearing target warts (P-
value <0.00001) versus placebo. Three of the 4 trials assessed response of distant warts showing a
risk ratio of 0.28 [95% CI: 0.08, 0.96] and a significant difference (P=0.04) versus placebo. Pain and
flu-like symptoms were the most common side effects with no recurrence seen after 3-6 months.
MMR vaccine
• Kaur A, Brar BK, Kumar S, Brar SK, Boparai AS, Puri N. A randomized
comparative study of MIP and MMR vaccine for the treatment of
cutaneous warts. Indian Journal of Dermatology. 2021 Mar
MIP intralesional injections have a quicker response and are more
efficacious compared to MMR in the treatment of Cw, though each
vaccine carries its own sets of side effects.
• No RCT comparing PPD to MMR

• For treatment of Molluscum Contagiosum with MMR, no RCT exists.

HIV
 Vaccines against Mycobacterium leprae
• Bacillus calmette-guérin (BCG)

• Indian cancer research center (ICRC) bacilli

• Killed Mycobacterium leprae

• Mycobacterium indicus pranii (earlier known as mycobacterium w)

• Mycobacterium vaccae

• Mycobacterium Habana

• Penicillin‑binding protein- ML0018c

• Recombinant protein, linking four M. leprae antigens: ML2531, ML2380,

ML2055, and ML2028

 ICRC Bacilli
• Cultivable leprosy derived mycobacteria (M. avium intracellulare complex ) was
prepared in 1979 at the Cancer Research Institute, Mumbai
1. Persistent immune conversion in 53% of LL patients on chemotherapy
2. 'upgrading' of tissue reaction and accelerated clearance of bacilli from the tissues of the patients.
3. 10% had post-vaccination reversal reactions, 1/3 with a high bacillary index developed ENL 10-
15 days after vaccination.
4. No fresh nerve lesions were observed in the vaccinated patients.
5. Immune conversion in 95% of lepromin-negative healthy subjects in endemic area and the
conversion was found to be stable for 5 years

Deo MG, et al. Antileprosy potentials of ICRC vaccine. A study in patients and healthy volunteers. Int J Lepr 1983
Deo MG, et al. Potential anti-leprosy vaccine from killed ICRC bacilli a clinicopathological study. Ind J Med Res 198
Convit J, et al. Investigations related to the development of a leprosy vaccine. Int J Lepr 1983
Convit J, et al. Vaccination in leprosy-observations and interpretations Int J Lepr 1980
Chaturvedi RM, et al. Effects of ICRC anti-leprosy vaccine in healthy subjects. Int J Lepr 1987 (100 km from Mubai, field
conditions)
ICRC vs BCG vs BCG+HKML vs M.w(MIP)
Gupte MD, et al. Comparative leprosy vaccine trial in south
India. Indian Journal of Leprosy. 1998
1,71,400 volunteered to participate in the study..BCG+ killed M. leprae provided
64% protection (CI 50.4-73.9), ICRC provided 65.5% protection (CI 48.0-77.0), M.w
gave 25.7% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI 13.5-49.8).
Protection observed with the ICRC vaccine and the combination vaccine (BCG+
killed M. leprae) meets the requirement of public health utility and these vaccines
deserve further consideration for their ultimate applicability in leprosy prevention.
BCG
• BCG was introduced as a vaccine for tuberculosis (TB) in 1921. The
beneficial effect in leprosy was suggested for the 1st time by
Fernandez in 1939
• In the 1960s, four major prospective trials were conducted in Karimui
(Papua New Guinea), Uganda, Burma, and India.Protection accorded
by BCG vaccine varied widely between these studies, reporting 80%
protection against leprosy in Uganda, 48% protection in Karimui, 30%
in South India, and only 20% protection in Burma.
BCG
• Setia et al.
• Average protective effect- 26% to 61%
• MB> PB
• Efficacy independent of age of vaccination, improved with multiple doses

• Zodpey et al. - avg protective effect (43% to 62%)

• Merle et al.
• Average protective effect- 41% to 60%
• MB = PB
• Revaccination one or twice did not provide any advantage
• Efficacy for vaccination after age of 15 years-doubtful.
BCG (Modifications)
• BCG + Killed M. leprae
• Convit et al (Venezuela) – No advantage over BCG alone
• Karonga prevention trial group (Malawi) – No adv over BCG
• Gupte et al. (South India) – 64%(BCG+HKML)> 34.1 (BCG)
• Recombinant BCG
• Overproducing MMP II, Ag85A Decreases replication in mouse footpad
 MIP(Mycobacterium indicus pranii)
Mycobacterium w - a non-pathogenic, rapidly growing atypical mycobacterium

• Protective efficacy of 68.6%, 59%, and 39.3% in HHCs at the end of the first,
second, and third follow-up survey, respectively, which was at 3, 6, and 9 years
after the initial vaccination.
• Addition of MIP vaccine to standard MDT resulted in faster clinical recovery and
faster bacillary clearance in MB leprosy.
• Increase in Type 1 reactions presumably due to upgraded CMI but no increase in
sensory-motor impairment.
• The effect of vaccine was found sustained for a period of about 7–8 years
• Approved by the Drugs Controller General of India and FDA. NLEP has introduced
MIP vaccine in a pilot project mode in India from the year 2016 in five highly
endemic districts (in Bihar and Gujarat) for contacts of cases, following which it
will cover 163 districts . Both patient and his contacts will receive two doses of MIP
Other anti leprosy vaccines
• M. vaccae – showed efficacy similar to BCG in Eastern Africa
• M. Habana

• Lepvax- a hybrid recombinant protein, linking four M. leprae

antigens: ML2531, ML2380, ML2055, and ML2028 (LEP-F1),
formulated in a stable emulsion with a synthetic, TLR4 agonist (GLA-
SE) as adjuvant. Has completed phase 1 clinical trials.
Some interesting vaccines in the works
• Cutaneous leishmaniasis - recombinant parasitic protein, adjuvants
such as CpG oligodeoxynucleotide motifs promoting IL‑12
release,killed Leishmania amazonensis, BCG (Preclinical)

• Melanoma
• CTCL
• Propionobacterium acnes
Edward Jenner
performing the
first ever
vaccination on
James Phipps
Circa 14 May 1796
THANK YOU
• Sharma P, Misra RS, Kar HK, Mukherjee A, Poricha D, Kaur H, et al. Mycobacterium w vaccine, a useful adjuvant to
multidrug therapy in multibacillary leprosy: A report on hospital based immunotherapeutic clinical trials with a follow-
up of 1-7 years after treatment. Lepr Rev. 2000;71:179-92.
• Zaheer SA, Mukherjee R, Ramkumar B, Misra RS, Sharma AK, Kar HK, et al. Combined multidrug and Mycobacterium w
vaccine therapy in patients with multibacillary leprosy. J Infect Dis. 1993;167:401-10.
• Talwar GP, Zaheer SA, Mukherjee R, Walia R, Misra RS, Suresh NR, et al. Immunotherapeutic effects of a vaccine based
on a saprophytic cultivable mycobacterium, Mycobacterium w in multibacillary leprosy patients. Vaccine. 1990;8:121
• 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.
• Kamal R, Natrajan M, Katoch K, Aroroa M. Clinical and histopathological evaluation of the effect of addition of
immunotherapy with Mw vaccine to standard chemotherapy in borderline leprosy. Indian J Lepr. 2012;84:287-306.
• [Google Scholar]
• Kamal R, Pathak V, Kumari A, Natrajan M, Katoch K, Kar HK. 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.