Vaccination

1. Vaccination Level 8 LECTURE 12

2. What is a “Vaccine” • The term vaccine derives from Edward Jenner's 1796 use of the term cow pox(Latin)variolavaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against infection ( smallpox )

3. Vaccine- Definition • A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. Vaccines include, for example, suspensions of killed or attenuated microorganisms, or products or derivatives of microorganisms. The most common method of administering vaccines is by injection, but some are given by mouth or nasal spray.

4. Vaccine stimulates Immune System • A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters

5. Vaccination • Practice of artificially inducing immunity • Goal of vaccination: • Stimulate both cell mediated and antibody mediated immunity that will protect the vaccinated person against future exposure to pathogen • Want the vaccine to have: • Maximum realism • Minimum danger

6. Viral vaccines What are the parameters necessary for the eradication of a virus? • The virus must have no alternative hosts • Infection (or vaccination) must produce lifelong immunity

7. Immunisation: the most generally applicable method of preventing infectious disease. Vaccinate: to administer, as a single or multiple dose, a nonpathogenic antigen (intact virus or virion subunit) to an animal or human such that the immune system of the individual responds by producing antibodies (humoral immunity) and in some cases, cell-mediated immunity directed against one, several, or all viral antigens.

8. Immunizations • Two artificial methods to make an individual immune to a disease • Active immunization-administration of a vaccine so that the patient actively mounts a protective immune response • Passive immunization-individual acquires immunity through the transfer of antibodies formed by an immune individual or animal

9. Requirements of a vaccine • The effective vaccine should be capable of eliciting the following ;- • Activation of Antigen-Presenting Cells to initiate antigen processing and producing interleukins. • Activation of both T and B cells to give a high yield of memory cells. • Generation of Th and Tc cells to several epitopes, to overcome the variation in the immune response in the population due to MHC polymorphism. • Persistence of antigen, probably on dendritic follicular cells in lymphoid tissue, where B memory cells are recruited to form antibody-secreting cells that will continue to produce antibody. Live vaccines fulfill these criteria par excellence.

10. Elimination of the disease will leave many T and B cells to convert into memory cells • Recovering from the infection leaves you with a supply of memory cells that will protect against future infection

11. Different Types of Vaccine • Whole virus vaccines. either live or killed, constitute the vast majority of vaccines in use at present. However, recent advances in molecular biology had provided alternative methods for producing vaccines. Listed below are the possibilities;-   • Live whole virus vaccines • Killed whole virus vaccines • Subunit vaccines;- purified or recombinant viral antigen • Recombinant virus vaccines •  Anti-idiotype antibodies • DNA vaccines

12. 1-Live attenuated virus vaccines • Preparation of Live attenuatedorganisms which have been passed repeatedly in tissue culture or chick embryos so that they have lost their capacity to cause disease, but retained an ability to induce antibody response, such as measles, rubella, mumps, yellow fever. • Successful live attenuated vaccines are effective for 3 reasons: • The attenuated viruses replicate to some extent in the host • The attenuated viruses have a reduced capacity to spread from the site of replication • The attenuated viruses cause mild or inapparent disease.

13. Delivery of live attenuated viruses: • Injection (e.g. measles-mumps-rubella vaccine) • Oral (e.g. poliovirus, rotavirus, adenovirus vaccines) • Nasal spray (respiratory viruses) • Potential problems: • Virus shedding and infection of unvaccinated individuals • Difficulty in prediction of behaviour in individuals and the population: • elimination before induction of protective response • infection of new niches in host • Ensuring purity and sterility • Advantages of Attenuated Vaccines I • Activates all phases of immune system. Can get humoral IgG and local IgA • Raises immune response to all protective antigens • More durable immunity; more cross-reactive

14. Advantages of Attenuated Vaccines II • Low cost • Quick immunity in majority of vaccinees • In case of polio and adeno vaccines, easy administration • Can lead to elimination of wild type virus from the community • Disadvantages of Live Attenuated Vaccine • Mutation; reversion to virulence (often frequent) • Spread to contacts of vaccinee who have not consented to be vaccinated (could also be an advantage in communities where vaccination is not 100%) • Spread vaccine not standardized--may be back-mutated • Problem in immunodeficiency disease (may spread to these patients)

15. Recombinant DNA approaches to attenuation from Flint et al. (2000) Principles of Virology ASM Press

16. 2-Inactivated (“killed”) Virus Vaccines • Inactivated or killedorganisms which have been killed by heat or chemicals but retain and ability to induce antibody response. They are generally safe but less efficacious than live vaccines and require multiple doses; e.g. polio , influenza, rabies • Chemical inactivation: • formalin - traditionally used; now being supplanted by: • b-propiolactone, ethylenimines • nonionic detergent-disruption • Advantages: • non-infectious • relatively uncomplicated and inexpensive to produce • killed virus more easily stored than live-virus vaccines • Gives sufficient humoral immunity if boosters given • No mutation or reversion • Can be used with immuno-deficient patients

17. Disadvantages of inactivated vaccines • Many vaccinees do not raise immunity • Boosters needed • No local immunity (important) • Failure in inactivation and immunization with virulent virus • Injection of large amounts necessary to elicit antibody response • Vaccine must be injected (no oral delivery) • Multiple rounds of immunisation required • Vaccination does not result in complete immunity

18. 3-Subunit vaccines (synthetic vaccines) • Recombinant DNA methods: • Clone appropriate viral genes into nonpathogenic host to produce immunogenic protein. • Example: Hepatitis B subunit vaccine (HBsAg) • Advantages: • no contamination of vaccine with original virus (nontoxic, nonallergenic) • inexpensive production of viral proteins in quantity • feasible even if virus cannot be cultured • Disadvantages: • lack of sufficient immune response • IgA response rarely stimulated • requires adjuvant • -------------------------------------------------------------------------------- • 4-Synthetic peptides (~20 amino acids in length): • Identification of immunogenic viral protein • Cloning and sequencing of gene encoding this protein • Synthesis of short peptides corresponding to sections in sequence • Test for immune response • Advantages: extremely safe, well-defined • Disadvantages: expensive; weak and short-lived antibody response; requires adjuvant; single-epitope vaccine will readily select mutants

19. antibody 5-Anti-idiotype vaccine Virus epitope Antibody with epitope binding site • Chemically synthesized peptide • malaria • poorly immunogenic

20. Anti-idiotypeantibody antibody Anti-idiotype vaccine cont Make antibody against antibody idiotype Anti-idiotype antibody mimics the epitope

21. Anti-idiotype antibody cont 2 Anti-idiotypeantibody Anti-anti-idiotypeantibody Anti-anti-idiotypeantibody Anti-anti-idiotypeantibody Use anti-idiotype antibody as injectable vaccine Use as vaccine Binds and neutralizes virus Antibody to anti-idiotype antibody

22. 6-DNA Vaccines • Plasmids are easily manufactured in large amounts • DNA is very stable • DNA resists temperature extremes so storage and transport are straight forward • DNA sequence can be changed easily in the laboratory. This means that we can respond to changes in the infectious agent • Mixtures of plasmids could be used that encode many protein fragments from a virus/viruses so that a broad spectrum vaccine could be produced • The plasmid does not replicate and encodes only the proteins of interest • There will be no immune response against the vector itself

23. DNA vaccines • Viral vectors: • Use nonpathogenic virus to immunise host against a pathogenic virus. • Merges subunit vaccine and live attenuated virus technologies. • Provides “benefit” of viral infection with respect to the immune response without the pathogenesis associated with the virulent virus. • Vaccinia virus: smallpox eradication; continued use as viral vector • Problems: • host is immunised against viral vector as well as the vaccine antigen subsequent uses of vector may result in weak/no response, or an immunopathological response. • Immunocompromised individuals may be infected within the vaccinated population with adverse consequences.

24. Construction of a recombinant vaccinia virus expressing the influenza virus HA gene from Flint et al. (2000) Principles of Virology ASM Press

25. DNA vaccines from Flint et al. (2000) Principles of Virology ASM Press

26. An ideal Vaccine should be …. Good immune response • Both Cell Mediated Immunity and antibody responses. • Immunity is long lived • Single dose Safety • Danger of reversion to virulence, or Severe disease in immunocomprised Stability • Organisms in the vaccine must remain viable in order to infect and replicate in the host • Vaccine preparations are therefore very sensitive to adverse storage conditions • Maintenance of the cold chain is very important. Expense • Cheap to prepare