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Viral VaccinesViral Vaccines
DrVishal KulkarniDrVishal Kulkarni
MBBS MD(Microbiology)MBBS MD(Microbiology)
Vaccine- DefinitionVaccine- Definition
 A vaccine is any preparation intended toA vaccine is any preparation intended to
produce immunity to a disease byproduce immunity to a disease by
stimulating the production of antibodies.stimulating the production of antibodies.
 It include suspensions of killed orIt include suspensions of killed or
attenuated microorganisms, or products orattenuated microorganisms, or products or
derivatives of microorganisms.derivatives of microorganisms.
Types of VaccinesTypes of Vaccines
 Whole organism vaccine-Whole organism vaccine-
 Measles, mumps, polioMeasles, mumps, polio
 Purified MacromoleculesPurified Macromolecules
 HBsAg vaccineHBsAg vaccine
 Recombinant Vector vaccinesRecombinant Vector vaccines
 Vaccinia virus for smallpox, salmonella,Vaccinia virus for smallpox, salmonella,
canarypoxcanarypox
 DNA vaccinesDNA vaccines
 Herpes virus, AIDSHerpes virus, AIDS
 Multivalent subunit vaccines-Multivalent subunit vaccines-
 Measles, HIV, Influenzae vaccineMeasles, HIV, Influenzae vaccine
LIVE VIRAL VACCINESLIVE VIRAL VACCINES
 Advantages-Advantages-
 Single dose is sufficientSingle dose is sufficient
 Administered through natural routeAdministered through natural route
 Induce wide spectrum of immunoglobulinInduce wide spectrum of immunoglobulin
 Induce CMIInduce CMI
 More effective & more long lastingMore effective & more long lasting
 Economical & ConvenientEconomical & Convenient
 Disadvantages-Disadvantages-
 Risk of reversion to virulenceRisk of reversion to virulence
 Contamination with dangerous virusContamination with dangerous virus
 Heat labile (refrigeration)Heat labile (refrigeration)
KILLED VACCINESKILLED VACCINES
 Are prepared by inactivating viruses withAre prepared by inactivating viruses with
heat, phenol, formalin, BPLheat, phenol, formalin, BPL
 Advantages-Advantages-
 Stability, safetyStability, safety
 Can be given in combinationCan be given in combination
 No danger of spread of virusNo danger of spread of virus
 Disadvantages-Disadvantages-
 Multiple injections are requiredMultiple injections are required
 Local & CMI are not inducedLocal & CMI are not induced
PASSIVE IMMUNIZATIONPASSIVE IMMUNIZATION
 Indicated in those who are at riskIndicated in those who are at risk
 Gives temporary protectionGives temporary protection
 E.g measles, mumps , Hepatitis, rabiesE.g measles, mumps , Hepatitis, rabies
 Generally combined immunization is givenGenerally combined immunization is given
 Viral vaccine in common useViral vaccine in common use
Live Killed
Poliomyelitis Poliomyelitis
Yellow fever Rabies
Varicella JE
Mumps, measles, rubella Hepatitis B (Cloned)
Influenza Influenza
Hepatitis vaccinesHepatitis vaccines
Hepatitis A vaccinesHepatitis A vaccines ::
 Inactivated, whole-cell Virus vaccines.Inactivated, whole-cell Virus vaccines.
 Grown in human diploid fibroblast cells.Grown in human diploid fibroblast cells.
 Full course consist of 2 i.m injectionsFull course consist of 2 i.m injections
Protection last for 10-20yrs.Protection last for 10-20yrs.
Hepatitis-B vaccine:Hepatitis-B vaccine:
 Hbs ag vaccineHbs ag vaccine: 1: 1stst
vaccine prepared fromvaccine prepared from
pooled plasma of healthy human carrier.pooled plasma of healthy human carrier.
Immunogenic but unsafe.Immunogenic but unsafe.
 Genetically engineered vaccineGenetically engineered vaccine::
S gene of HBV cloned in bakers yeast.S gene of HBV cloned in bakers yeast.
Consist only non glycosylated Hbs ParticlesConsist only non glycosylated Hbs Particles
Alum is used as adjuvant.Alum is used as adjuvant.
Dose –Dose –
3 doses at 0,1,6 months, i.m into deltoid.3 doses at 0,1,6 months, i.m into deltoid.
 In infants into anterolateral aspect of thigh.In infants into anterolateral aspect of thigh.
Polio vaccinePolio vaccine::
 Killed polio vaccine (salk):Killed polio vaccine (salk):IPV.IPV.
Formalin inactivated preparation of three types ofFormalin inactivated preparation of three types of
polio virus grown in monkey kidney tissue culture.polio virus grown in monkey kidney tissue culture.
Dose:Dose: 3 doses 4-6 wks apart , booster after 63 doses 4-6 wks apart , booster after 6
months later.months later.
Provides 80-90% protection.Provides 80-90% protection.
 Live polio vaccine: (OPV).Live polio vaccine: (OPV).
 Attenuated strain are grown in monkeyAttenuated strain are grown in monkey
kidney Cell.kidney Cell.
 Issued in monovalent or trivalent form MgCl2Issued in monovalent or trivalent form MgCl2
or sucrose used as stabilizer.or sucrose used as stabilizer.
 ContainsContains
 Type 1 virus- 10 lakhType 1 virus- 10 lakh
 Type 2 virus – 2 lakhType 2 virus – 2 lakh
 Type 3 virus- 3 lakhType 3 virus- 3 lakh
 Dose – 3 doses in 4-6 wk intervalDose – 3 doses in 4-6 wk interval
Antirabies vaccineAntirabies vaccine::
 Neural vaccineNeural vaccine::
• SempleSemple
• BPLBPL
• Infant brain vaccineInfant brain vaccine
 Non neural vaccine :Non neural vaccine :
• Egg vaccines-Egg vaccines-
- duck egg vaccine- duck egg vaccine
- live attenuated chick embryo vaccine- live attenuated chick embryo vaccine
• Tissue culture vaccine-Tissue culture vaccine-
- Human diploid cell vaccine.- Human diploid cell vaccine.
- Purified Chick Embryo Cell Vaccine (PCEC) .- Purified Chick Embryo Cell Vaccine (PCEC) .
- Purified Vero Cell Vaccine (PVC).- Purified Vero Cell Vaccine (PVC).
Zoster vaccineZoster vaccine
 It is a lyophilized preparation of the Oka strain ofIt is a lyophilized preparation of the Oka strain of
live, attenuated VZV.live, attenuated VZV.
 Give in children 1-12 yrs old.Give in children 1-12 yrs old.
 Single 0.65-mL s.c in the deltoid region of the upperSingle 0.65-mL s.c in the deltoid region of the upper
armarm
 VZIG in immunodeficient & elderyVZIG in immunodeficient & eldery
JAPANESE B ENCEPHALITIS VACCINEJAPANESE B ENCEPHALITIS VACCINE::
 Inactivated JE vaccine (Nakayama strain):Inactivated JE vaccine (Nakayama strain): derivedderived
from infected mouse brain. licensed in Japan sincefrom infected mouse brain. licensed in Japan since
1954.1954.
 JE strain 14-14-2JE strain 14-14-2 - Similar mouse brain derived JE- Similar mouse brain derived JE
vaccinesvaccines
 produced in primary hamster kidney cellsproduced in primary hamster kidney cells
 2 doses i.m. 1 yr apart2 doses i.m. 1 yr apart
Vaccine against HPVVaccine against HPV::
 BivalentBivalent human papilloma virus vaccine( HPV2)-human papilloma virus vaccine( HPV2)-
 Contains types 16 and 18 aloneContains types 16 and 18 alone
 QuadrivalentQuadrivalent human papilloma virusVaccin(HPV4)human papilloma virusVaccin(HPV4)
--covers four serotypes of HPV, 16 ,18, & 6covers four serotypes of HPV, 16 ,18, & 6
and 11and 11..

Ideal age for Vaccination and efficacy:Ideal age for Vaccination and efficacy:
• The duration of the immunity conferred by theThe duration of the immunity conferred by the
vaccines is not yet known..vaccines is not yet known..
• The best subjects for vaccination will beThe best subjects for vaccination will be
pre adolescents or adolescentspre adolescents or adolescents..
 Contraindicated in pregnancyContraindicated in pregnancy
SWINE FLU VACCINESWINE FLU VACCINE
FDA approved H1 N1 vaccinesFDA approved H1 N1 vaccines
 Influenza A (H1N1) 2009 Monovalent Vaccine
 Indications And Usage
 an inactivated influenza virus vaccine persons ≥6 months of
age
 Children 4- 9 years of age: Two 0.5-mL i.m. injections, 1
month apart
 > 10 yrs- 0.5 ml single dose i.m
HIV Vaccine ApproachesHIV Vaccine Approaches
Challenges in HIV Vaccine ResearchChallenges in HIV Vaccine Research
• Viral Genetic DiversityViral Genetic Diversity:: HIVHIV
is not just one specificis not just one specific
virus.virus.
• Neutralizing AntibodyNeutralizing Antibody::
Difficult to generateDifficult to generate
broadly neutralizingbroadly neutralizing
antibodies.antibodies.
• Vaccine TestingVaccine Testing:: SlowSlow
process, very expensiveprocess, very expensive
Status of HIV Vaccine DevelopmentStatus of HIV Vaccine Development
product Company HIV
subtype
Phase Site
Peptide
V3 peptide
CIBG B 1 Cuba
Recombinant subunit
Bivalent rpg 120
VaxGen B+E 3 Thailand
Live viral vector
Canary pox - env-gag-pr
Aventis B 1 Uganda
Live bacterial vector
Salmonella - env
Univ. Md. B 1
Combinations (Vector
prime + subunit boost)
Canary pox - env-gag-pr,
• Nef, pol rgp 120
• rgp 120
Canary pox - env gag-pr
Aventis E
2
Chiron
VaxGen
Aventis
E
E
B+E
B
2
2
Thailand
Haiti,
Thailand,
Brazil
Several other antiviral vaccines are available:Several other antiviral vaccines are available:
 MeaslesMeasles
 RubellaRubella
 MumpsMumps
 MMRMMR
 Yellow feverYellow fever
Vaccines under trialVaccines under trial
 DengueDengue
 KFDKFD
 EbolaEbola
 SARSSARS
 RotavirusRotavirus
 Swine influenzaSwine influenza
Thank you….!!Thank you….!!

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Viral vaccine long

  • 1. Viral VaccinesViral Vaccines DrVishal KulkarniDrVishal Kulkarni MBBS MD(Microbiology)MBBS MD(Microbiology)
  • 2. Vaccine- DefinitionVaccine- Definition  A vaccine is any preparation intended toA vaccine is any preparation intended to produce immunity to a disease byproduce immunity to a disease by stimulating the production of antibodies.stimulating the production of antibodies.  It include suspensions of killed orIt include suspensions of killed or attenuated microorganisms, or products orattenuated microorganisms, or products or derivatives of microorganisms.derivatives of microorganisms.
  • 3. Types of VaccinesTypes of Vaccines  Whole organism vaccine-Whole organism vaccine-  Measles, mumps, polioMeasles, mumps, polio  Purified MacromoleculesPurified Macromolecules  HBsAg vaccineHBsAg vaccine  Recombinant Vector vaccinesRecombinant Vector vaccines  Vaccinia virus for smallpox, salmonella,Vaccinia virus for smallpox, salmonella, canarypoxcanarypox
  • 4.  DNA vaccinesDNA vaccines  Herpes virus, AIDSHerpes virus, AIDS  Multivalent subunit vaccines-Multivalent subunit vaccines-  Measles, HIV, Influenzae vaccineMeasles, HIV, Influenzae vaccine
  • 5. LIVE VIRAL VACCINESLIVE VIRAL VACCINES  Advantages-Advantages-  Single dose is sufficientSingle dose is sufficient  Administered through natural routeAdministered through natural route  Induce wide spectrum of immunoglobulinInduce wide spectrum of immunoglobulin  Induce CMIInduce CMI  More effective & more long lastingMore effective & more long lasting  Economical & ConvenientEconomical & Convenient  Disadvantages-Disadvantages-  Risk of reversion to virulenceRisk of reversion to virulence  Contamination with dangerous virusContamination with dangerous virus  Heat labile (refrigeration)Heat labile (refrigeration)
  • 6. KILLED VACCINESKILLED VACCINES  Are prepared by inactivating viruses withAre prepared by inactivating viruses with heat, phenol, formalin, BPLheat, phenol, formalin, BPL  Advantages-Advantages-  Stability, safetyStability, safety  Can be given in combinationCan be given in combination  No danger of spread of virusNo danger of spread of virus
  • 7.  Disadvantages-Disadvantages-  Multiple injections are requiredMultiple injections are required  Local & CMI are not inducedLocal & CMI are not induced
  • 8. PASSIVE IMMUNIZATIONPASSIVE IMMUNIZATION  Indicated in those who are at riskIndicated in those who are at risk  Gives temporary protectionGives temporary protection  E.g measles, mumps , Hepatitis, rabiesE.g measles, mumps , Hepatitis, rabies  Generally combined immunization is givenGenerally combined immunization is given
  • 9.  Viral vaccine in common useViral vaccine in common use Live Killed Poliomyelitis Poliomyelitis Yellow fever Rabies Varicella JE Mumps, measles, rubella Hepatitis B (Cloned) Influenza Influenza
  • 10. Hepatitis vaccinesHepatitis vaccines Hepatitis A vaccinesHepatitis A vaccines ::  Inactivated, whole-cell Virus vaccines.Inactivated, whole-cell Virus vaccines.  Grown in human diploid fibroblast cells.Grown in human diploid fibroblast cells.  Full course consist of 2 i.m injectionsFull course consist of 2 i.m injections Protection last for 10-20yrs.Protection last for 10-20yrs.
  • 11. Hepatitis-B vaccine:Hepatitis-B vaccine:  Hbs ag vaccineHbs ag vaccine: 1: 1stst vaccine prepared fromvaccine prepared from pooled plasma of healthy human carrier.pooled plasma of healthy human carrier. Immunogenic but unsafe.Immunogenic but unsafe.  Genetically engineered vaccineGenetically engineered vaccine:: S gene of HBV cloned in bakers yeast.S gene of HBV cloned in bakers yeast. Consist only non glycosylated Hbs ParticlesConsist only non glycosylated Hbs Particles Alum is used as adjuvant.Alum is used as adjuvant. Dose –Dose – 3 doses at 0,1,6 months, i.m into deltoid.3 doses at 0,1,6 months, i.m into deltoid.  In infants into anterolateral aspect of thigh.In infants into anterolateral aspect of thigh.
  • 12. Polio vaccinePolio vaccine::  Killed polio vaccine (salk):Killed polio vaccine (salk):IPV.IPV. Formalin inactivated preparation of three types ofFormalin inactivated preparation of three types of polio virus grown in monkey kidney tissue culture.polio virus grown in monkey kidney tissue culture. Dose:Dose: 3 doses 4-6 wks apart , booster after 63 doses 4-6 wks apart , booster after 6 months later.months later. Provides 80-90% protection.Provides 80-90% protection.
  • 13.  Live polio vaccine: (OPV).Live polio vaccine: (OPV).  Attenuated strain are grown in monkeyAttenuated strain are grown in monkey kidney Cell.kidney Cell.  Issued in monovalent or trivalent form MgCl2Issued in monovalent or trivalent form MgCl2 or sucrose used as stabilizer.or sucrose used as stabilizer.
  • 14.  ContainsContains  Type 1 virus- 10 lakhType 1 virus- 10 lakh  Type 2 virus – 2 lakhType 2 virus – 2 lakh  Type 3 virus- 3 lakhType 3 virus- 3 lakh  Dose – 3 doses in 4-6 wk intervalDose – 3 doses in 4-6 wk interval
  • 15. Antirabies vaccineAntirabies vaccine::  Neural vaccineNeural vaccine:: • SempleSemple • BPLBPL • Infant brain vaccineInfant brain vaccine  Non neural vaccine :Non neural vaccine : • Egg vaccines-Egg vaccines- - duck egg vaccine- duck egg vaccine - live attenuated chick embryo vaccine- live attenuated chick embryo vaccine
  • 16. • Tissue culture vaccine-Tissue culture vaccine- - Human diploid cell vaccine.- Human diploid cell vaccine. - Purified Chick Embryo Cell Vaccine (PCEC) .- Purified Chick Embryo Cell Vaccine (PCEC) . - Purified Vero Cell Vaccine (PVC).- Purified Vero Cell Vaccine (PVC).
  • 17. Zoster vaccineZoster vaccine  It is a lyophilized preparation of the Oka strain ofIt is a lyophilized preparation of the Oka strain of live, attenuated VZV.live, attenuated VZV.  Give in children 1-12 yrs old.Give in children 1-12 yrs old.  Single 0.65-mL s.c in the deltoid region of the upperSingle 0.65-mL s.c in the deltoid region of the upper armarm  VZIG in immunodeficient & elderyVZIG in immunodeficient & eldery
  • 18. JAPANESE B ENCEPHALITIS VACCINEJAPANESE B ENCEPHALITIS VACCINE::  Inactivated JE vaccine (Nakayama strain):Inactivated JE vaccine (Nakayama strain): derivedderived from infected mouse brain. licensed in Japan sincefrom infected mouse brain. licensed in Japan since 1954.1954.  JE strain 14-14-2JE strain 14-14-2 - Similar mouse brain derived JE- Similar mouse brain derived JE vaccinesvaccines  produced in primary hamster kidney cellsproduced in primary hamster kidney cells  2 doses i.m. 1 yr apart2 doses i.m. 1 yr apart
  • 19. Vaccine against HPVVaccine against HPV::  BivalentBivalent human papilloma virus vaccine( HPV2)-human papilloma virus vaccine( HPV2)-  Contains types 16 and 18 aloneContains types 16 and 18 alone  QuadrivalentQuadrivalent human papilloma virusVaccin(HPV4)human papilloma virusVaccin(HPV4) --covers four serotypes of HPV, 16 ,18, & 6covers four serotypes of HPV, 16 ,18, & 6 and 11and 11.. 
  • 20. Ideal age for Vaccination and efficacy:Ideal age for Vaccination and efficacy: • The duration of the immunity conferred by theThe duration of the immunity conferred by the vaccines is not yet known..vaccines is not yet known.. • The best subjects for vaccination will beThe best subjects for vaccination will be pre adolescents or adolescentspre adolescents or adolescents..  Contraindicated in pregnancyContraindicated in pregnancy
  • 21. SWINE FLU VACCINESWINE FLU VACCINE FDA approved H1 N1 vaccinesFDA approved H1 N1 vaccines  Influenza A (H1N1) 2009 Monovalent Vaccine  Indications And Usage  an inactivated influenza virus vaccine persons ≥6 months of age  Children 4- 9 years of age: Two 0.5-mL i.m. injections, 1 month apart  > 10 yrs- 0.5 ml single dose i.m
  • 22. HIV Vaccine ApproachesHIV Vaccine Approaches
  • 23. Challenges in HIV Vaccine ResearchChallenges in HIV Vaccine Research • Viral Genetic DiversityViral Genetic Diversity:: HIVHIV is not just one specificis not just one specific virus.virus. • Neutralizing AntibodyNeutralizing Antibody:: Difficult to generateDifficult to generate broadly neutralizingbroadly neutralizing antibodies.antibodies. • Vaccine TestingVaccine Testing:: SlowSlow process, very expensiveprocess, very expensive
  • 24. Status of HIV Vaccine DevelopmentStatus of HIV Vaccine Development product Company HIV subtype Phase Site Peptide V3 peptide CIBG B 1 Cuba Recombinant subunit Bivalent rpg 120 VaxGen B+E 3 Thailand Live viral vector Canary pox - env-gag-pr Aventis B 1 Uganda Live bacterial vector Salmonella - env Univ. Md. B 1 Combinations (Vector prime + subunit boost) Canary pox - env-gag-pr, • Nef, pol rgp 120 • rgp 120 Canary pox - env gag-pr Aventis E 2 Chiron VaxGen Aventis E E B+E B 2 2 Thailand Haiti, Thailand, Brazil
  • 25. Several other antiviral vaccines are available:Several other antiviral vaccines are available:  MeaslesMeasles  RubellaRubella  MumpsMumps  MMRMMR  Yellow feverYellow fever
  • 26. Vaccines under trialVaccines under trial  DengueDengue  KFDKFD  EbolaEbola  SARSSARS  RotavirusRotavirus  Swine influenzaSwine influenza

Editor's Notes

  1. The purified virus is then formalin inactivated and adsorbed to aluminum hydroxide. Havrix and Twinrix have 2-phenoxyethanol added as a preservative, whereas Vaqta is preservative free .full course consist of 2 i.m injections.protection last for 10-20yrs.
  2. 22nm Hbs ag particles are seperated by ultacentrifugation and inactivated with formaldehyde , urea or proteinase.a special vaccine containing all antigenic components of HbsAg (pres1,pres2 and s) has been developed.gives greater seroconversion. Hepatitis B vaccines are effective and safe. Up to 95% of vaccinated individuals form effective antibodies when they get the vaccine and are protected from hepatitis B. In healthcare workers, high-risk public safety workers, dialysis patients, and sexual partners of infected persons
  3. (PCEC)Primary cell culture vaccine gronwn in chick embryo. PVC Purified Vero Cell Vaccine-Continuous cell culture vaccine grown in vero cell line derived from kidney of vervet monkey or african green monkey(cercopithecus aethiops).
  4. Because HPV is spread by sexual contact, and the high-risk years for infection are roughly from ages 18 to 25,
  5. Past approaches to vaccine strategies directed against HIV have included attenuated and inactivated virus, but the high risk and safety limitations afforded to these traditional approaches have led to the exploration of novel vaccine strategies, such as a viral vector-based approach. The success with vaccination against other viruses is a window of optimism, and the over 10 HIV vaccine trials currently ongoing include the use of alphavirus, vaccinia, and adenoviral vectors, in addition to DNA plasmid, protein subunit, and peptide vaccines.