2. Viral Vaccine Types

4. Viruses are inactivated with chemicals such as formaldehyde. Inactivated (killed) vaccines cannot cause an infection, but they still can stimulate a protective immune response. Inactivated Virus Vaccines

5. Split Vaccine

6. Subunit Vaccines

7. Use of a related virus from another animal - the earliest example was the use of cowpox to prevent smallpox. Administration of pathogenic or partially attenuated virus by an unnatural route - the virulence of the virus is often reduced when administered by an unnatural route. This principle is used in the immunization of military recruits against adult respiratory distress syndrome using enteric- coated live adenovirus types 4 & 7. Passages of the virus in an “unnatural host” or host cell - The major vaccines used in man and animals have all been derived this way. Attenuated Virus Vaccines The pathogenic virus is isolated from a patient and grown in human cultured cells The cultured virus is used to infect monkey cells The virus acquires many mutations that allow it to grow well in monkey cells The virus no longer grows well in human cells (it is attenuated) and can be used as a vaccine

8. Attenuation can be achieved more rapidly and reliably with recombinant DNA techniques Isolate pathogenic virus Isolate virulence gene Mutate virulence gene Delete virulence gene Receptor- binding protein Virulence Core proteins Resulting virus is viable, immunogenic but avirulent. It can be used as a vaccine.

9. Experimental Vaccines DNA Vaccines Recombinant Vector Vaccines

11. Problems in viral vaccine development Different types of virus may cause similar diseases – (common cold) Antigenic drift and shift (Influenza) Large animal reservoirs Integration of viral DNA Transmission from cell to cell Recombination and mutation of the vaccine virus in an attenuated vaccine

13. Greatest triumph is the eradication of smallpox from the planet, with no naturally-occurring cases having been found since 1977

14. (only if there is a lack of animal reservoir for virus) Large-scale vaccination campaigns can be successful Leroy EM, Kumulungui B, Pourrut X, et al.. Fruit bats as reservoirs of Ebola virus. Nature 2005;438:575-576.