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Vaccinology
- 1. Vaccinology Asst.prof .Dnyaneshwari Joshi. Department of Biotechnology and winetechnology .
- 2. Vaccine suspension of weakened, killed, or fragmented microorganisms or toxins or of antibodies or lymphocytes that is administered primarily to prevent disease.
- 3. History- The 1st experiment performed by Louis Pasteur on July 6,1885(1st well established vaccine) -Edward Jenner is known as a father of vaccinology and immunology - 1950-1970 is considered as a golden age of vaccinology, - Vaccines for rubella, polio, measles, mumps were developed during this years.
- 5. 1.PASSIVE IMMUNIZATION -Passive immunization may be used as follows: -To prevent disease after a known exposure (e.g., needle stick injury with blood that is contaminated with hepatitis B virus [HBV]) -To ameliorate the symptoms of an ongoing disease -To protect immunodeficient individuals
- 6. 2.ACTIVE IMMUNIZATION TO INDUCE IMMUNITY AND MEMORY -Active immunization can be achieved by natural infection with a microorganism, or it can be acquired artificially by administration of a vaccine. -In active immunization, the immune system plays an active role— proliferation of antigen-reactive T and B cells is induced and results in the formation of protective memory cells. -This is the primary goal of vaccination.
- 7. • Vaccination is not 100% effective. • With any vaccine, a small percentage of recipients will respond poorly and therefore will not be adequately protected. • This problem can be overcome if the majority of the population is immune to an infectious agent, significantly reducing the pathogen reservoir. • In this case, the chance of a susceptible individual contacting an infected individual is very low. This phenomenon is known as herd immunity
- 9. 1.LIVE ATTENUATED VACCINES • Live vaccines are prepared with organisms limited in their ability to cause disease (e.g., avirulent or attenuated organisms). • Live vaccines are especially useful for protection against infections caused by enveloped viruses, which require T-cell immune responses for resolution of the infection. • Immunization with a live vaccine resembles the natural infection in that the immune response progresses through the natural innate, TH1,and then TH2 immune responses, and humoral, cellular, and memory • immune responses are developed. • Immunity is generally long lived and, depending on the route of administration, can mimic the normal immune response to the infecting agent.
- 10. Microorganisms can be attenuated so that they lose ability to cause significant disease • Retain capacity for growth in host • A virus might be grown in cell type that is not normal • Accumulates mutations that might weaken it • Measles, mumps, rubella vaccine is example
- 11. Different approaches to the development of attenuated virus vaccines 1. Most attenuated virus strains have been derived by ‘hit and miss’ procedures such as repeated passage of wild-type virus in cells unrelated to the normal host. This selects mutants that are better suited for growth in the abnormal culture conditions than in the natural host. Eg. Polio Vaccine 2. ‘Cold-adapted’ virus strains-These have been derived by incubating virus-infected cell cultures at temperatures below the optimum for virus replication. ‘Cold-adapted’ virus strains with reduced virulence have been used in influenza and respiratory syncytial virus vaccines, though the latter were not sufficiently attenuated for use in children. 3. Reassortants -Rotavirus reassortants have been produced, with some genes derived from a human virus and some from an animal virus. 4. Reverse genetics-The power of reverse genetics has been used to develop a respiratory syncytial virus vaccine by engineering into the virus genome mutations that attenuate virulence
- 12. • Example; • Oral polio vaccine (OPV) • It is designed by Albert Sabin, consisting of three attenuated strains of poliovirus, is administered orally to children. • The attenuated viruses colonize the intestine and induce production of secretory IgA, an important defense against naturally acquired poliovirus. • The vaccine also induces IgM and IgG classes of antibody and ultimately protective immunity to all three strains of virulent poliovirus. • Unlike most other attenuated vaccines, OPV requires boosters, because the three strains of attenuated poliovirus interfere with each other’s replication in the intestine.
- 14. With the first immunization, one strain will predominate in its growth, inducing immunity to that strain. With the second immunization, the immunity generated by the previous immunization will limit the growth of the previously predominant strain in the vaccine, enabling one of the two remaining strains to colonize the intestines and induce immunity. Finally, with the third immunization, immunity to all three strains is achieved.
- 15. Disadvantage: The following list includes three problems with live vaccines: 1. The vaccine virus may still be dangerous for immunosuppressed people or pregnant women, who do not have the immunologic resources to resolve even a weakened virus infection. 2. The viability of the vaccine must be maintain. 3. The vaccine may revert to a virulent viral form. The rate of reversion of the OPV is about 1 case in 2.4 million doses of vaccine. This reversion can also allow pathogenic forms of the virus to find their way into the water supply, especially in areas where sanitation is not rigorous or wastewater must be recycled. The projected eradication of paralytic polio may be impossible as long as OPV is used anywhere in the world.
- 17. Inactivated,orkilled,virusvaccinesaremadeby-massproducingthevirulentvirusand theninactivatingtheinfectivity,usuallybytreatmentwithachemicalsuchasformaldehyde Aimofinactivation-completelyinactivatesthevirus,butleavesitsantigenicitysufficientlyunchangedthatthey canstillstimulateaprotectiveimmuneresponse Inactivated(killed)virusvaccinesaremadefrompreparationsofvirulentviruses,soitisessentialthatall infectivityisdestroyed. Examples 1.Salk vaccine- killed polio vaccine Thetreatmentinvolvessuspendingvirionsinformalin(formaldehydesolution)at370Cforabout10days. Otherexamplesofkilledvirusvaccinesarethosecontaininginactivatedvirionsofinfluenza,hepatitisAand footandmouthdiseaseviruses. Virususedtoproduceaninactivatedvaccineisavirulentstrain,itisvitalthat100%oftheinfectivityis destroyedintheproductionprocess. 3. Killed vaccine:
- 18. • COVAXIN,IndiasindigenousCOVID-19vaccinebyBharatBiotechisdeveloped incollaborationwiththeIndianCouncilofMedicalResearch(ICMR)– NationalInstituteofVirology(NIV).(Jan3_) Theindigenous,inactivatedvaccineisdevelopedandmanufacturedinBharatBiotech'sBSL-3(Bio-SafetyLevel3)highcon tainmentfacility. Thevaccineisdevelopedbyusing Whole -VirionInactivatedVero Cell derivedplatformtechnology.Inactivatedvaccinesdonot replicateandarethereforeunlikelytorevertandcausepathologicaleffects.Theycontaindeadvirus,incapableofinfecting peoplebutstillabletoinstructtheimmunesystemtomountadefensivereactionagainstaninfection. InactivationisdonebyusingchemicalBeta-propiolactonethiscompounddisablesthevirusbybindingtoits genes,thenmixedwithaluminiumbasedadjuventmolecules. • 2.Covaxin (Bharat biotech ):
- 22. 5.Recombinant Vaccine :Virus like particles Virus-likeparticlesarestructuresassembledfromvirusproteins. Theparticlesresemblevirions,buttheyaredevoidofanynucleicacidandcantherefore bedeemedsaferthanvaccinescontainingattenuatedorinactivatedvirions. HepatitisBvirus(HBV)vaccineisproducedinrecombinantyeastcellsthathavethegene fortheHBsAginsertedintothegenome. Thecellsaregrowninbulkandthenbrokentoreleasethevirusprotein. AfterpurificationtheHBsAgmoleculesreceiveachemicaltreatmentthatcausesthemto aggregate. ThesubunitproteinsusedintheHBVandthehumanpapillomavirus(HPV)vaccinesform viruslikeparticles(VLPs),whicharemoreimmunogenicthanindividualproteins
- 23. TheUniversityofOxfordpartneredwiththeBritish-Swedishcompany AstraZenecato developandtestacoronavirusvaccineknownasChAdOx1 nCoV-19orAZD1222.A largeclinicaltrialshowedthevaccineoffered strongprotection,withanoverallefficacyof79percent Example: COVISHIELD – SERUM INSTITUTE INDIA
- 34. Human alphaherpesvirus3 (HHV-3) is knownas Varicella-zoster virus (VZV), whichis the causativeagent of varicella (chickenpox) and herpeszoster(shingles). Zostavax®is the vaccinelicensedfor herpeszosterpreventionin individualsabovethe age of 50. It is a lyophilizedpreparation whichis givenas subcutaneousinjection. A non-replicating liposome-basedsubunitvaccine(HZ/su)is the new development for zosterprevention.
- 35. smallmolecules,knownashaptens,canbemadeimmunogenicafter conjugationtocarrierproteinsThisprinciplehassincebeenapplied successfullytoimprovetheimmunogenicityof(poly)saccharides 10.Conjugate vaccine : A conjugate vaccine is a type of vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.
- 37. 11. T-cell vaccine: It is a vaccinedesignedto induceprotectiveT-cells. T-cell vaccinesare designedto inducecellular immunity.They are also referred to ascell-mediatedimmune(CMI) vaccines.
- 38. HPV is a causal factor for multiple cancers and diseases. •Preventative HPV vaccine is not effective at clearing preexisting infections. •Therapeutic and T cell based HPV vaccines typically target oncoproteins E6 and E7. •Several clinical trials have been performed to assess the efficacy of the vaccines. •More trials are expected as new strategies to enhance vaccine potency are developed.