Functional Immunogenicity of Baculovirus Expressing Pfs25, a Human Malaria Transmission-blocking Vaccine Candidate Antigen

We have focused on development of a novel vaccine vector based on "Baculophage", a baculovirus display system for expression of proteins on the surface of the viral envelope, as a non-pathogenic and non-vertebrate insect virus. In the present study, recombinant baculovirus (AcNPV-Pfs25surf) were generated, which displayed Pfs25, a potent Plasmodium falciparum transmission-blocking vaccine candidate. Both intranasal and intramuscular immunizations of mice with AcNPV-Pfs25surf induced high levels of Pfs25-specific antibodies, which strongly reacted with ookinetes of transgenic Plasmodium berghei expressing Pfs25 (TrPfs25Pb). Importantly, sera obtained from immunized rabbits exhibited a significant transmission-blocking effect (>90% reduction in infection intensity) in standard membrane feeding assay using P. falciparum gametocytes. Additionally, active immunization (both intranasal and intramuscular routes) of mice followed by challenge using TrPfs25Pb demonstrated an effective transmission-blocking response, with an 83% (intranasal) and ∼95% (intramuscular) reduction in oocyst intensity, respectively. Thus, the baculovirus-based vaccines offer a promising new alternative to current human vaccine delivery platforms for the development of malaria multi-stage vaccines.