Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission

Abstract

We have recently developed a new experimental vaccine vector system based on Autographa californica nucleopolyhedrosis virus (AcNPV) termed the "Baculovirus Dual Expression System", which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. The present study used this system to generate a Plasmodium vivax transmission-blocking immunogen (AcNPV-Dual-Pvs25). AcNPV-Dual-Pvs25 not only displayed Pvs25 on the AcNPV envelope, exhibiting aspects of its native three-dimensional structure, but also expressed appropriately immunogenic protein upon transduction of mammalian cells. Both intranasal and intramuscular immunization of mice with AcNPV-Dual-Pvs25 induced high Pvs25-specific antibody titres, notably of IgG1, IgG2a and IgG2b isotypes, indicating a mixed Th1/Th2 response. Importantly, sera obtained from subcutaneously immunized rabbits exhibited a significant transmission-blocking effect (96% reduction in infection intensity, 24% reduction in prevalence) when challenged with human blood infected with P. vivax gametocytes using the standard membrane feeding assay. Additionally, active immunization (both intranasal and intramuscular routes) of mice followed by challenge using a transgenic P. berghei line expressing Pvs25 in place of native Pbs25 and Pbs28 (clone Pvs25DR3) demonstrates a strong transmission-blocking response, with a 92.1% (intranasal) and 83.8% (intramuscular) reduction in oocyst intensity. Corresponding reductions in prevalence of infection were observed (88.4% and 75.5% respectively). This study offers a novel tool for the development of malarial transmission-blocking vaccines against the sexual stages of the parasite, using the Baculovirus Dual Expression System that functions as both a subunit, and DNA based vaccine.