Many genomes from infectious agents have now been sequenced. Reverse vaccinology takes advantage of this information to find new antigens for use in immunization (Fig. 6.24). The primary research begins with cloning each of the genes from the infectious organism into an expression library. All the proteins are expressed, isolated, purified, and then screened in mice for immune response. Each protein is tested for stimulating the immune system and for its ability to protect the mice from the actual infectious agent. The proteins that elicit the best response can either be combined into a subunit vaccine or used as separate vaccines.
Reverse vaccinology has been used to create a vaccine for Neisseria meningitidis serogroup B, which is a major cause of meningitis in children. Attenuated bacteria were not effective as vaccines, and until the sequencing of the N. meningitidis genome, no vaccine was available. A library of 350 different N. meningitidis proteins was expressed in and purified from E. coli. These were individually screened for their presence on the surface of the bacteria using ELISA and FACS. Surface proteins were then screened for immune effectiveness. Of the 350 tested proteins, only 29 became potential candidates and are currently being developed into a vaccine. Without the ability to sequence genomes, vaccine development was often impossible, but now new and emerging diseases can be studied to find potential vaccines.
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