Recombinant subunit vaccines: potentials and constraints.
Recombinant DNA techniques have enormous potential for the development of inexpensive, safe and efficacious vaccines for the aquaculture industry. Aside from rationally attenuated pathogens, two broad categories of recombinant vaccines have been described. The first are so-called "vectored" vaccines, which consist of either viral or plasmid expression vectors harbouring genes for protective antigens from a given pathogen. The second are recombinant subunit antigens produced using heterologous protein expression systems. Less onerous from a regulatory standpoint, recombinant subunit vaccines generate strong antibody responses in recipient animals when administered parenterally with adjuvant-containing formulations. This approach is nevertheless constrained by the fact that low-cost systems for protein expression (especially E. coli, but also yeast) often generate misfolded or incorrectly processed membrane antigens that fail to protect, while more complex insect and mammalian tissue culture cells are prohibitively expensive from a production standpoint. Furthermore, subunit antigens generate less than optimal mucosal and cytotoxic T-cell responses, the last two of which are especially important for the clearance of intracellular pathogens. Fortunately, these constraints are now being overcome through the use of new generation adjuvants and delivery systems that enhance immunogenicity, as well as new expression systems for the production of viral and protozoan membrane antigens.
Clark
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Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. tgc3@cornell.edu
Cassidy-Hanley
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D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000378:metabolism*; D017756:Aquaculture / Q000379:methods*; D002478:Cells, Cultured; D004926:Escherichia coli; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D015003:Yeasts
D000276:Adjuvants, Immunologic; D000941:Antigens; D019444:Vaccines, DNA; D022223:Vaccines, Subunit