Protective efficacy of a Plasmodium vivax circumsporozoite protein-based vaccine in Aotus nancymaae is associated with antibodies to the repeat region

• Published in: PLoS neglected tropical diseases 2014-10, Vol.8 (10), p.e3268-e3268
• Main Authors: Yadava, Anjali, Hall, Cysha E, Sullivan, JoAnn S, Nace, Douglas, Williams, Tyrone, Collins, William E, Ockenhouse, Christian F, Barnwell, John W
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; Antibodies, Protozoan - blood; Antibodies, Protozoan - immunology; Antigens; Aotidae - immunology; Aotidae - parasitology; Biology and Life Sciences; Female; Immunity, Humoral - immunology; Immunogenetics; Immunoproteins; Infections; Macaca mulatta; Malaria; Malaria vaccine; Malaria Vaccines - immunology; Malaria, Vivax - immunology; Malaria, Vivax - parasitology; Malaria, Vivax - prevention & control; Male; Mice; Monkey Diseases - parasitology; Monkey Diseases - prevention & control; Monkeys & apes; Plasmodium vivax; Plasmodium vivax - immunology; Proteins; Protozoan Proteins - immunology; Random Allocation; Studies; Toll-Like Receptor 9 - immunology; Vaccination; Vaccines; Vaccines, Synthetic - immunology
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003268

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.