2. Inactivated whole virus vaccines

These were the easiest preparations to use. The preparation was simply inactivated. The outer virion coat should be left intact but the replicative function should be destroyed. To be effective, non-replicating virus vaccines must contain much more antigen than live vaccines that are able to replicate in the host. Preparation of killed vaccines may take the route of heat or chemicals. The chemicals used include formaldehyde or beta- propiolactone. The traditional agent for inactivation of the virus is formalin. Excessive treatment can destroy immunogenicity whereas insufficient treatment can leave infectious virus capable of causing disease. Soon after the introduction of inactivated polio vaccine, there was an outbreak of paralytic poliomyelitis in the USA use to the distribution of inadequately inactivated polio vaccine. This incident led to a review of the formalin inactivation procedure and other inactivating agents are now available, such as Beta-propiolactone. Another problem was that SV40 was occasionally found as a contaminant and there were fears of the potential oncogenic nature of the virus.
 

Live vs Dead vaccines

Feature                 Live         Dead

Dose low high

no. of doses             single         multiple

need for adjuvant         no               yes

Duration of immunity     many years        less

antibody response         IgG,          IgA IgG

CMI                       good             poor

Reversion to virulence   possible not     possible

Because live vaccines replicate inside host cells, bits of virus antigen are presented to the cell surface and recognized by cytotoxic cells

Potential safety problems

Live vaccines

1. Underattenuation
2. Mutation leading to reversion to virulence
3. Preparation instability
4. Contaminating viruses in cultured cells
5. Heat lability
6. Should not be given to immunocompromized or pregnant patients

Killed vaccines

1. Incomplete inactivation
2. Increased risk of allergic reactions due to large amounts of antigen involved

Present problems with vaccine development include

1. Failure to grow large amounts of organisms in laboratory
2. Crude antigen preparations often give poor protection. eg. Key antigen not identified, ignorance of the nature of the protective or the protective immune response.
3. Live vaccines of certain viruses can  (1). induce reactivation, (2) be oncogenic in nature