Protective Efficacy of a Plasmodium vivax Circumsporozoite Protein-Based Vaccine in Aotus nancymaae Is Associated with Antibodies to the Repeat Region

Abstract

We have previously reported that Vivax Malaria Protein 001 (VMP001), a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax, is immunogenic in mice and rhesus monkeys in the presence of various adjuvants. In the present study, we evaluated the immunogenicity and efficacy of VMP001 formulated with a TLR9 agonist in a water-in-oil emulsion. Following immunization, the vaccine efficacy was assessed by challenging Aotus nancymaae monkeys with P. vivax sporozoites. Monkeys from both the low- and high-dose vaccine groups generated strong humoral immune responses to the vaccine (peak median titers of 291,622), and its subunits (peak median titers to the N-term, central repeat and C-term regions of 22,188; 66,120 and 179,947, respectively). 66.7% of vaccinated monkeys demonstrated sterile protection following challenge. Protection was associated with antibodies directed against the central repeat region. The protected monkeys had a median anti-repeat titer of 97,841 compared to 14,822 in the non-protected monkeys. This is the first report demonstrating P. vivax CSP vaccine-induced protection of Aotus monkeys challenged with P. vivax sporozoites.

Development of vaccines for Plasmodium vivax malaria

“…Sixty six percent of vaccinated monkeys were completely protected following challenge with P. vivax sporozoites. Antibodies against the repeat region of PvCSP showed a statistical association with protection [38]. VMP001 has also been formulated in nanoparticles formed as interbilayer crosslinked multilamellar lipid vesicles (ICMVs) composed of polylactide-co-glycolide acid (PLGA) and a lipid membrane [39,40].…”

Recent Developments in Malaria Vaccinology

“…The superior immunogenicity of particulate or arrayed malaria antigens in the context of VLPs (in comparison to soluble antigen) is consistent across a number of subunit vaccine development efforts for different life cycle stages. Indeed, a more recent comparison of VLPs versus soluble antigen for P. vivax CSP showed similar results in NHPs (Vanloubbeeck et al, 2013), with promising efficacy reported in Aotus monkeys (Yadava et al, 2014).…”

Rationale for Further Development of a Vaccine Based on the Circumsporozoite Protein of Plasmodium vivax

“…Unlike the P . falciparum vaccine, it underwent additional extensive testing and was advanced into humans following two separate, preclinical immunogenicity [10] and efficacy [11] studies conducted in nonhuman primates.…”