1. Virus vaccines LECTURE 17: Viro100: Virology 3 Credit hours NUST Centre of Virology & Immunology Waqas Nasir Chaudhry

2. The term vaccination is derived from the Latin word “vacca” meaning cow This is because the original procedure involved the inoculation of material from cowpox lesions into healthy people Edward Jenner Cowpox and small pox “A vaccine contains material intended to induce an immune response, and this may involve both B cells (which develop into antibody producing cells) and T cells (responsible for cell mediated immunity)” Immunological memory Polio, rubella, rabies and foot and mouth disease HIV-1, hepatitis C, Ebola and the herpes simplex viruses

3. Vaccines Types 1.Live attenuated virus vaccines 2.Inactivated virus vaccines 3.Virion subunit vaccines 4.Live recombinant virus vaccines 5.Virus like particles 6.Synthetic peptide vaccines 7.DNA vaccines

4. Live attenuated virus vaccines A live attenuated vaccine contains a mutant strain of a virus that has been derived from a wild type virulent strain There are increasing amounts of virus antigen in the body as the virus replicates 1.First, its antigens must be identical, or very similar, to those of the wild type virus so that an immune response against the vaccine virus provides protection from infection with the wild type virus 2.The virulence of the wild type virus must have been attenuated; in other words the vaccine virus must have little or no virulence

5. “hit and miss” Repeated passage of wild type virus in cells unrelated to the normal host The vaccine strains of the three serotypes of poliovirus Which are attenuated as a result of their loss of ability to infect neurones, were derived from wild type strains by passage in monkeys and in monkey kidney cell cultures Albert Sabin did this pioneering work

6. Derivation of attenuated poliovirus strain (Sabin type 1) from wild- type poliovirus strain

7. 1.Cold adapted virus strains 2.Reassortants 3.Reverse genetics Risks in using a live vaccine – During virus replication, nucleotide substitutions might occur, resulting in reversion to virulence – It is also possible that recombinants between vaccine strains and wild type strains may be formed Because of these risks many countries switched from using attenuated polio vaccine to inactivated vaccine

8. Inactivated virus vaccines Inactivated, or killed Made by mass producing the virulent virus and then inactivating the infectivity, usually by treatment with a chemical such as formaldehyde Jonas Salk developed a treatment for poliovirus that led to the development of the vaccine that bears his name The treatment involves suspending virions in formalin (formaldehyde solution) at 37 ◦ C for about 10 days Influenza, hepatitis A and foot and mouth disease viruses

9. Because the virus used to produce an inactivated vaccine is a virulent strain, it is vital that 100 percent of the infectivity is destroyed in the production process The need for complete inactivation was under- lined in the US in 1955 when four million doses of inadequately inactivated Salk vaccine were inoculated into children Amongst the vaccinees there were 204 cases of paralytic polio and 11 deaths A similar problem occurred when there were out- breaks of foot and mouth disease in France and the UK

10. Virion subunit vaccines A subunit vaccine contains purified components of virions In the case of influenza the vaccines contain the haemagglutinin (H) and neuraminidase (N) surface glycoproteins The infectivity of a batch of influenza virions is inactivated with formaldehyde or β –propiolactone For protection against influenza the subunit vaccines are preferred over the inactivated vaccines as they cause fewer side-effects, especially in children The subunit vaccines induce poorer immune responses, so two doses are necessary to provide adequate immunity

11. Haemagglutinin (H) and neuraminidase (N) are extracted from inactivated influenza virions and purified by sucrose gradient centrifugation. The bands from the gradient are harvested and incorporated into the vaccine

12. Branched Genome