Inactivated Viral Vaccines

The first report of “virus” inactivation for vaccine purposes was described in 1886 when Daniel Elmer Salmon and Theobald Smith immunized pigeons with what they thought was a heat-killed hog cholera “virus” (Salmon and Smith 1886). Although in reality it was a cholera-like bacterium, it seeded the scientific community with evidence that immunization with inactivated pathogens can provide protection against infectious disease. Research continued for at least 15 years when at the beginning of the twentieth century the first killed (bacterial) vaccines for humans were developed for typhoid fever, cholera, and plague (Wright and Semple 1897; Haffkine 1899). The foundations of immunization with inactivated virus preparations were also laid at the end of the nineteenth century with Pasteur’s partially inactivated rabies virus (Pasteur et al. 1885), which was cultured in rabbit spinal cords. However, inactivated viral vaccine development was only truly launched with the discovery of cell culture procedures that supported the replication of viral pathogens in vitro, outside the host organism, thus allowing the large scale production of viruses as a source for whole inactivated vaccines. This breakthrough was attributed to Enders, Weller, and Robbins who received the Nobel Prize in 1954 for their discovery on how to cultivate poliovirus in fibroblasts in vitro (Enders et al. 1949; Weller et al. 1949). In general, all inactivated viral vaccines follow a similar production course in which the pathogen is first cultivated on a substrate to produce large quantities of antigen. Historically, vaccine manufacturers have been using primary cells, tissues,