Virus vaccines

LECTURE 17:

Viro100: Virology3 Credit hoursNUST Centre of Virology & Immunology

Waqas Nasir Chaudhry

• 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

Vaccines Types

1. Live attenuated virus vaccines2. Inactivated virus vaccines3. Virion subunit vaccines4. Live recombinant virus vaccines5. Virus like particles6. Synthetic peptide vaccines7. DNA vaccines

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

• “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

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

1. Cold adapted virus strains2. Reassortants3. 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

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

• 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

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

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

Branched Genome