Baculovirus-Derived Vectors for Immunization and Therapeutic Applications

Baculoviruses are arthropod-specific, enveloped viruses with circular, supercoiled double-stranded deoxyribonucleic acid genomes. While many viruses are studied to seek solutions for their adverse impact on human, veterinary, and plant health, the study of baculoviruses was stimulated initially by their potential utility to control insect pests. Later, the utility of baculovirus as gene expression vectors was evidenced leading to numerous applications. Several strategies are employed to obtain recombinant viruses that express large quantities of heterologous proteins. A major step forward was the development of bacmid technology (the construction of bacterial artificial chromosomes containing the genome of the baculovirus) which allows the manipulation of the baculovirus genome in bacteria. With this technology, foreign genes can be introduced into the bacmid by homologous and site-directed recombination or by transposition. Baculoviruses have been used to explore fundamental questions in molecular biology such as the nature of programmed cell-death. Moreover, the ability of baculoviruses to transduce mammalian cells led to the consideration of their use as gene-therapy and vaccine vectors. Strategies for genetic engineering of baculoviruses have been developed to meet the requirements of new application areas. Display of foreign proteins on the surface of virions or in nucleocapsid structures, the assembly of expressed proteins to form virus-like particles or protein complexes have been explored and validated as vaccines. The aim of this chapter is to update the areas of application of the baculoviruses in protein expression, alternative vaccine designs and gene therapy of infectious diseases and genetic disorders. Finally, we review the baculovirus-derived products on the market and in the pipeline for biomedical and veterinary use.