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

Anjali Yadava,Christian F Ockenhouse,William E Collins,John W Barnwell,Cysha E Hall,Tyrone Williams,Joann S Sullivan,Douglas Nace,Mauricio Martins Rodrigues

doi:10.1371/journal.pntd.0003268

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.

Highlights

The range of Plasmodium vivax transmission spans 95 countries putting 2.86 billion people at risk for this malaria parasite [1] and causes an estimated 132–391 million infections each year [2]
Plasmodium vivax is responsible for causing malaria in large parts of the globe, including regions with temperate climates not suited for the transmission of other Plasmodium species
P. vivax has the propensity to form dormant forms, known as hypnozoites, that can remain latent for weeks to months and reactive periodically to cause recurrent infections

Summary

Introduction

The range of Plasmodium vivax transmission spans 95 countries putting 2.86 billion people at risk for this malaria parasite [1] and causes an estimated 132–391 million infections each year [2]. In addition to its widespread distribution, P. vivax has the propensity to form dormant hypnozoites in the liver, which reactivate periodically and result in recurring relapse infections. Bennett and colleagues reported an association between decreased activity of the CYP2D6 isoenzyme and reduced metabolism of PQ resulting in treatment failure [4]. This further reduces the pool of individuals who may be treated with PQ, reinforcing the need to develop a vaccine to prevent P. vivax malaria. Resources for vivax research remain limited, with only 5% of malaria funds directed toward P

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