Vaccines for viral and parasitic diseases produced with baculovirus vectors

Abstract

The baculovirus-insect cell expression system is an approved system for the production of viral antigens with vaccine potential for humans and animals and has been used for production of subunit vaccines against parasitic diseases as well. Many candidate subunit vaccines have been expressed in this system and immunization commonly led to protective immunity against pathogen challenge. The first vaccines produced in insect cells for animal use are now on the market. This chapter deals with the tailoring of the baculovirus-insect cell expression system for vaccine production in terms of expression levels, integrity and immunogenicity of recombinant proteins, and baculovirus genome stability. Various expression strategies are discussed including chimeric, virus-like particles, baculovirus display of foreign antigens on budded virions or in occlusion bodies, and specialized baculovirus vectors with mammalian promoters that express the antigen in the immunized individual. A historical overview shows the wide variety of viral (glyco)proteins that have successfully been expressed in this system for vaccine purposes. The potential of this expression system for antiparasite vaccines is illustrated. The combination of subunit vaccines and marker tests, both based on antigens expressed in insect cells, provides a powerful tool to combat disease and to monitor infectious agents.

Fig 1

Flow chart showing four different methods to make a vaccine based on your favorite gene (YFG) in the baculovirus expression system: (1) protein expression in insect cell bioreactors using the polyhedrin locus for expression, (2) protein expression in insect larvae leaving the polyhedrin gene intact; expression is driven either by a duplicated p10 promoter or by the original p10 promoter, (3) baculovirus surface display methods where YFG is fused to GP64, and (4) DNA vectors with a mammalian promoter (mp) for synthesis of your favorite gene product (YFGP) in the target species. Subsequent steps in the process are: (A) selection and PCR amplification of YFG, (B) cloning into the appropriate baculovirus vector, (C) generation of recombinant BV particles or occlusion bodies, (D) production in insect cells in bioreactors or larvae, (E) purification of recombinant YFGP or collection of BVs loaded with either YFGP or YFG, and (F) delivery of prophylactic or therapeutic vaccines.