title: 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.
authors.affiliation: Malaria Vaccine Branch, Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
authors.affiliation: Malaria Vaccine Branch, Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Cysha E
authors.initials: CE
authors.lastname: Hall
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: JoAnn S
authors.initials: JS
authors.lastname: Sullivan
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Nace
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Tyrone
authors.initials: T
authors.lastname: Williams
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Collins
authors.affiliation: Malaria Vaccine Branch, Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D016645:Aotidae / Q000276:immunology* / Q000469:parasitology; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008992:Monkey Diseases / Q000469:parasitology / Q000517:prevention & control; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011897:Random Allocation; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D051217:Toll-Like Receptor 9; D014614:Vaccines, Synthetic