2. VACCINES
• Vaccine is an immuno biological substance
designed to produce specific protection against a
given disease.
• It stimulate the production of protective
antibody and other immune mechanisms.
• Live vaccine
• killed
• toxoids
• cellular fractions
• Subunit & recombinant
3. • We will be discuss following
Leprosy
HPV
HSV
VZV
HIV
Melanoma
4. LEPROSY
• Vaccines have capacity to provoke an immune
response which enables the host to efficiently
deal with infecting organism.
• AIMS AT-
1. Achieving more efficient killing of viable bacilli
2. Faster clearance of dead bacilli
3. Reduce incidence and severity of reactions
4. Restoration of immunity-reducing relapse and
re-infection
5. Vaccines tried in leprosy
a) Mycobacterium bovis (BCG)
b) BCG + killed M.leprae
c) Mycobacterium w
d) ICRC bacillus
e) Mycobacterium vaccae
6. A) Mycobacterium bovis (BCG)
• Live attenuated vaccine
• Give along with MDT from beginning of treatment
and subsequently every 6 months; till the end of
treatment.
Effect-
• Faster smear negativity
• Faster fall in BI
• Incidence of reaction not increased
• Duration of reaction decreased.
• Rapid clearence of granuloma on histopathology
7. B) Mycobacterium w
Immuvac
• Rapid growing, non-pathogenic,saprophitic cultivable
mycobacteria.
• Mycobacterium indicum pranii
• Shares 65kd,18kd,13kd antigens with M.leprae &
M.tuberculosis
• Autoclaved heat killed vaccine
• Dose- 1st dose of 5 *109 baccili/0.1 ml saline
intradermaly
• Subsequently- half dose
• At beginning of MDT and repeated every 6 monthly
till 24 month.
• Availability –0.5 ml vial by cadila pharma (375 INR)
8. C) ICRC
• Isolated from leprosy patient
• Showed cross reactive antigens to M.leprae
• Killed vaccine
• S/E of leprosy vaccines are mainly local blister
/nodule formation at injection site which heal
with scar.
9. HPV vaccines
Prophylactic vaccines:
• Based on virus-like particles (VLP),which are recombinant
versions of major capsid protein (L1) of relevant HPV
types.
• A quadrivalent HPV vaccine has shown promising results
in the treatment of warts. However, the presence of only
previous reports, partial clearance in one of the two
studies and a limited access in resource-restricted
countries are the drawbacks of this vaccine.
11. • Available for use in women of 9 to 26 years of age (in US)
since June 2006; the vaccine was approved in November 2009
by the U.S. FDA for use in males 16 to 26 years old.
• Quadrivalent human papilloma virus (HPV) [types 6, 11, 16,
18] recombinant vaccine (Gardasil®; Silgard®) is composed of
virus-like particles (VLPs) formed by self-assembly of
recombinant L1 capsid protein from each of HPV types 6, 11,
16, and 18.
• The VLPs are noninfectious, containing no DNA, and are highly
immunogenic, inducing high levels of neutralizing antibodies
against the particular HPV types when administered to
animals or humans.
GARDASIL
12. GARDASIL Indications
• Prevention of vulvar and vaginal cancer
• Vaccination in females 9 through 26 years of age for prevention of the
following diseases caused by Human Papillomavirus (HPV) Types 6, 11, 16,
and 18:
– Cervical cancer
– Genital warts (condyloma acuminata) and the following precancerous
or dysplastic lesions:
• Cervical adenocarcinoma in situ (AIS)
• Cervical intraepithelial neoplasia (CIN) grade 1 ,2,3.
• Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3
• Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3
• Vaccination in boys and men 9 through 26 years of age for the prevention
of genital warts caused by HPV types 6 and 11
• Vaccination in people ages 9 through 26 years for the prevention of anal
cancer and associated precancerous lesions due to human papillomavirus
(HPV) types 6, 11, 16, and 18
13. GARDASIL SHORTCOMINGS
• Cannot protect from a disease that is caused by
other types of HPV
• Does not treat HPV infection.
• Cannot protect against HPV types that the patient
already has
• No correlation was found between antibody levels
and protective efficacy of the vaccine.
14. GARDASIL C/I
• Pregnancy
• Immunocompromised status like HIV
infection, cancer, drugs
• Fever over 100°F (37.8°C).
• h/o hypersensitivity to previous dose of
GARDASIL
15. • Availability: 0.5ml suspension (2800 INR) -
Merck
• Dosage schedule: 0.5-ml suspension for im
injection: 0, 2 months, 6 months
• INGREDIENTS:
Proteins of HPV Types 6, 11, 16, and 18,
amorphous aluminum hydroxyphosphate
sulfate, yeast protein, sodium chloride, L-
histidine, polysorbate 80, sodium borate, and
water for injection.
16. GARDASIL S/E
• Pain, swelling, itching, bruising, and redness at the
injection site
• headache
• fever
• nausea
• dizziness
• vomiting
• Syncope
17. CERVARIX
• Bivalent vaccine containing proteins of HPV 16,18
• The vaccine also contains 3-O-deacylted-4’-monophosphoryl
lipid A (MPL), aluminum hydroxide, sodium chloride, and
sodium dihydrogen phosphate dehydrate.
• CERVARIX contains no preservatives.
• The most common local adverse reactions ( 20% of subjects)
were pain, redness, and swelling at the injection site.
• The most common general adverse events ( 20% of subjects)
were fatigue, headache, myalgia, gastrointestinal symptoms,
and arthralgia.
• 0.5ml (2000 INR)Manufacturer:GSK
18. Therapeutic HPV vaccines
• A therapeutic vaccine composed of HPV-6 L2E7 fusion
protein and AS02A adjuvant was evaluated in
conjunction with conventional therapies in subjects
with anogenital warts.
• Three doses of vaccine or placebo were administered
along with either ablative therapy or podophyllotoxin.
• Therapeutic vaccination failed to increase the efficacy
of conventional therapies.
19. HSV
• The HSV candidiate vaccines tested until now were mostly
purified subunit vaccines and/or recombinant envelope
glycoproteins (gB, gD).
• The immunotherapeutic effect of herpes vaccines seem less
convincing.
• However introduction of new adjuvants , which shift the
cytokine production of helper T cells toward stimulation of
cytotoxic T cells (Th1), is a promising development.
• Three types of vaccines undergoing clinical trials-DISC (disabled
infection single cycle),adjuvant subunit and DNA vaccine.
20. • Several vaccines have shown promise in animal models;
however, so far these have not been successful in human
clinical studies.
• Prophylactic HSV vaccines have focused primarily on eliciting
antibody responses. Potent antibody responses are needed to
result in sufficiently high levels of virus-specific antibody in
the genital tract.
• Therapeutic vaccines that reduce recurrences need to induce
potent T-cell responses at the site of infection.
21. • Recently, two previous trials have suggested that
herpes simplex virus (HSV) type
glycoprotein D (gD) vaccine combined with
the adjuvants alum and 3'-O-deacylated-monophosphoryl
lipid A (MPL) is well tolerated, reduced the rate of
acquisition of genital herpes, but only in women with no
preexisting HSV antibody.
• The vaccine also did not add to the protection provided by
a previous HSV-1 infection in women.
22. Herpes Vaccines
• A candidate subunit vaccine, GEN-003/MM-2, was evaluated for its
ability to induce a broad-spectrum immune response in mice and
therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is
comprised of HSV-2 glycoprotein D2 (gD2rTMR(340-363)) and a
truncated form of infected cell polypeptide 4 (ICP4(383-766)),
formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2).
• The frequency of recurrent viral shedding was considerably
reduced in GEN-003/MM-2- but not in GEN-003 or MM-2
vaccinated animals.
• These findings suggest a possible role for immunotherapeutic
GEN-003/MM-2 vaccination as a viable alternative to chronic
antiviral drugs in the treatment and control of genital
herpes disease.
• Skoberne M, Cardin R, Lee A, et al. An Adjuvanted Herpes Simplex Virus Type 2
(HSV-2) Subunit Vaccine Elicits a T Cell Response In Mice and Is an Effective
Therapeutic Vaccine In Guinea Pigs. J Virol. 2013 Jan 30. Cambridge
23. Herpes Vaccines
• Veselenak et al described studies in the guinea pig model of genital
herpes to evaluate a novel plasmid DNA (pDNA) vaccine encoding
the HSV-2 glycoproteinD and UL46 and UL47 genes encoding
tegument proteins VP11/12 and VP 13/14 (gD2/UL46/UL47),
formulated with a cationic lipid-based adjuvant Vaxfectin.
• This novel adjuvanted pDNA vaccine has demonstrated both
prophylactic and therapeutic efficacy in the guinea pig model of
genital herpes and warrants further development.
• Veselenak RL, Shlapobersky M, Pyles RB et al. A Vaxfectin(®)-adjuvanted HSV-2
plasmid DNA vaccine is effective for prophylactic and therapeutic use in the guinea
pig model of genital herpes. Vaccine.2012 Nov 19;30(49):7046-51. Epub 2012 Oct
4. USA
24. Herpes Vaccines
• The purpose of this study was to investigate the potential
of intranasal immunization with non-ionic surfactant
vesicles (NISV) containing either the secretory recombinant
form of glycoprotein B (gBs) of herpes simplex virus type 1
or a related polylysine reach peptides (DTK) for induction of
protective immunity against genital herpes infection in
mice.
• Cortesi R, Ravani L, Rinaldi F, 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 Jan
20;440(2):229-37. Epub 2012 Jun 26. Italy.
25. Varicella vacccine
• Live attenuated VZV vaccine(Oka strain)
• ACIP & AAP recommanded it for children aged
12 months to 12 years for routine
immunization as 2 doses of 0.5 ml
S.C.seperated by 3 months started at 12 to 15
months of age.
• Duration of vaccine induced protection is not
known.
• This vaccine recently also found to be effective
in prevention of H.zoster & post herpatic
neuralgia in older adults(zoster vaccine)
27. ZOSTAVAX
• Live attenuated VZV (OKA strain)
• New vaccine to prevent herpes zoster in
individual older than 60 yrs available
commercially.
• It will not prevent post herpatic neuralgia.
• Dose-0.65 ml,S.C.
• S/E –GI disturbances,rash ,fever,injection site
reaction.
• Not available in india.
28. HIV vaccines
• Globally more than 50 vaccine candidates are
currently being studied & majority of them are
in early stages of clincal trials.
• Prophylactic vaccines-recominant
subunit,synthetic peptides,viral vectors,DNA
vaccines.
• Therapeutic vaccines.
29. Prophylactic vaccines
• In 1987,in USA gp160 envelope derived &
produced in baculovirus-insect cell system was
developed but tested on only few participants.
• In 1989 formalin inactivated whole simian
immunedeficiency virus (SIV) vaccine which
was known to confer protection in macaques
with AIDS developed.later it was found that
protection was due to antigens(HLA & β2
microglobulin) from human cells used for
growth of viral strain.
30. • In 1992,Live attenuated SIV vaccine was found
to be efffective in macaques but later due to
safety issue as itself caused AIDS in neonatal
macaques research stopped further.
• Paterson et al investigated multi-component
vaccine delivered by replication-competent
live vector Ad5hr-SIV recominants &
concluded it can persistently infect new cells
& continuously present low level antigen may
be advantageous in overcoming among
complex immunogens for immune recognition
& future vaccine design should focus on it
31. • Other live vector vaccines tested were
modified vaccinia ankara(MVA),canary
pox,lipopeptides,plasmid DNA.
• Supachai et al demonstrated efficasy of live
canarypox virus(ALVAC-HIV{vCP1521}) &
recombinant gp120 subunit vaccine
(AIDSVAX B/E) in randomized clinical trial in
population with large heterosexual
risk.although results shows only modest
benefit they offer insight for further research.
• Recombinant DNA/MVA vaccine by Pancea
biotech since 2005 under negotiation.
32. Therapeutic vaccines
• Vaccines are designed for HIV positive pt with
healthy immune system (CD4 count >250-350)
to mount good immune response against
them.
• Most of trials require recipient to continue
ART while on study.
• Derma Vir vaccine combines 3 elements
1.A pDNA expressing 15 HIV antigen
2.A synthetic pDNA nanomedicine formulation
3.Dendritic cell
33. • Natural transport by epidermal langerhans cell
to lymph nodes to express the pDNA –
encoded HIV antigens & induce
precourser/memory T cell with high
proliferation capacity has been consistently
demonstarted in mouse,rabbit human
subjects when adminstered topically.
• Viral vector based & dendritic cell targeted
protien vaccines are potential new vaccine
platform for future.
34. Melanoma vaccine
• Allogenic vaccines-from melanoma associated
antigens derived from large number of pt
prepared in cell culture lines.
e.G Canvaxin & mealcine
• Autologous vaccines-prepared from pt’s own
tumor cells.
• Ganglioside vaccine to stimulate B cell.
• Peptide vaccine to stimulate T cell.
35. Canvaxin
• 3 viable irradiated whole melanoma cell lines
choosen due to their high content of tumor
associated antigens such as MAGE-
1,3,tyrosinase,gp100,gp75,mart-1/melan-A.
• In trail,vaccine shown to enhance immune response
to melanoma.
36. Melacine
• Consist of lysate of 2 homogenized melanoma
cell lines with adjuvant DETOX.
• Trials results awaited.
• Most recently role of heat shock protein-
peptide complex,agonists of TLR9 ,monoclonal
antibody against CTLA4 are under research as
vaccines.
38. MMR
• Single or multiple, recalcitrant or non-recalcitrant
plantar warts.
• MMR vaccine was injected into single lesions or largest
wart in case of multiple lesions at 3-week intervals until
complete clearance or for a maximum of 3 treatments.
Follow-up was done every 3 months for 9 months to
detect any recurrence.
• Side effects include pain during injection (82.6%) and
flu-like symptoms.
• Availability-Morupar,trimovax,tresivac by Aventis &
Serum institute of india in prize b/w 75-96 INR.
• Gamil H, Elgharib I, Nofal A, Abd-Elaziz T. Intralesional immunotherapy of
plantar warts: report of a new antigen combination. J Am Acad Dermatol. 2010
Jul;63(1):40-3. doi: 10.1016/j.jaad.2009.07.023. Epub 2010 May 11.
39. Mumps, Candida, Trichophytin Ag
• Exclusion: Patients with prior allergic response to mumps
or Candida antisera, pregnancy, HIV infection, iatrogenic
immunosuppression, primary immunosuppression or any
generalized dermatitis.
• An intradermal injection of 0.1 ml of mumps
and Candida antigen was placed in the right and left
forearms, respectively. The amount of reaction was read
after 48 to 72 hours. Based on the size of test reaction, the
responder’s largest wart was treated with an intralesional
injection of mumps or Candida.
40. Mumps, Candida, Trichophytin Ag
• Flu-like symptoms (fever, malaise and myalgia) within 12
hours of intralesional injection of antigen that lasted up to 24
hours. Symptoms were treated with nonsteroidal anti-
inflammatories. The most common complaints were pain
upon intralesional injection and pruritus within the first 24
hours.
• It was concluded that immunotherapy should serve as first-
line treatment for immune individuals with numerous (>5) or
large (>1 cm) warts and as an effective second-line treatment
in immune individuals who are judged to have failed
cryotherapy.
• The mechanism of action for this type of immunotherapy was
proposed to be based on trauma and subsequent
inflammatory reaction of the intralesional injection leading
to an HPV-directed immunologic reaction
41. BCG
• Topical bacillus Calumette-Guérin treatment has been
attempted in the treatment of venereal warts.
• The mode of action is based on stimulation of the local
immune response.
• Complete response has been achieved in 60% to 92% of
patients treated after 1 or 2 cycles, and they remained
disease free after 6 to 9 months.
42. PPD
• In this study done in Egypt, Intradermal injection of PPD was
tried in the treatment of anogenital warts in pregnant women.
• A total of 40 pregnant women, aged 20-35 years, and presented
with anogenital warts were treated with weekly injections of
PPD given intradermally in the forearms, and evaluated for the
response regularly.
• Overall, the improvement in this study was 85% and was related
to the extent of tuberculin reactivity.
• Nineteen (47.5%) patients demonstrated complete clearance, 15
(37.5%) had partial response, and three (7.5%) had minimal
response. Three (7.5%) cases did not respond to treatment.
• Side effects were minimal and insignificant.
• Eassa BI, Abou-Bakr AA, El-Khalawany MA. Intradermal injection of PPD as a novel
approach of immunotherapy in anogenital warts in pregnant women. Dermatol
Ther. 2011 Jan-Feb;24(1):137-43. Egypt.
43. PPD
• All subjects were tested for existing immunity to tuberculin
antigen preparation by placing 0.1 ml intradermally into the
skin of the left forearm (pretest).
• The presence or absence and size of the ensuing reactions
were noted after 72 hours.
• Positive reaction required erythema and induration of at least
10 mm in diameter to ensure sufficient immunity to PPD-
tuberculin protein.
• Exclusion criteria: pregnancy, primary and iatrogenic
immunosuppression, or any generalized dermatitis, non-
reactive or <10mm
44. PPD
• Intralesional injection of tuberculin in a volume of 0.3 cc
deep in the largest 2 warts (based on surface area) and
repeated every 2 weeks until complete clearing of the
treated warts or for a maximum of 4 injections.
• Adverse effects: localized pruritus, erythema, crustation,
burning and pain,
• not severe enough to cause discontinuation of injection.