Figure 1.

Evolution of Vaccines. Prior to the introduction of vaccines, immunity developed following natural infection with a specific viral pathogen. Live attenuated vaccines often are developed from the wild-type pathogen after selecting for less virulent strains that are able to infect the host and elicit antiviral immunity, but with greatly reduced disease severity. In cases in which live attenuated vaccines have rare but serious adverse events, further refinement of the vaccine is provided by developing an inactivated formulation for immunization. This may consist of a whole virus vaccine that has been inactivated by formaldehyde (e.g., IPV), use of a non-replicating strain of virus (e.g., MVA), or replacement with a subunit vaccine consisting of only one or a few protective antigens (e.g., Hepatitis B surface antigen). The risk of morbidity or mortality is reduced as the immunogenic insult is modified from natural infection to attenuated infection, to immunization with an inactivated or non-replicating antigen. In some cases, such as in the development of the Hepatitis B vaccine, the intermediate step involving the development of an attenuated vaccine may be omitted if a non-replicating vaccine provides effective immunity.

Abbreviations: OPV; live oral polio vaccine, IPV; inactivated polio vaccine, MVA; Modified Vaccinia Ankura