title: Evaluation of the safety and immunogenicity in rhesus monkeys of a recombinant malaria vaccine for Plasmodium vivax with a synthetic Toll-like receptor 4 agonist formulated in an emulsion.
abstract: Plasmodium vivax is the major cause of malaria outside sub-Saharan Africa and inflicts debilitating morbidity and consequent economic impacts in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of a novel chimeric recombinant protein, VMP001, based on the circumsporozoite protein (CSP) of P. vivax. Very few adjuvant formulations are currently available for human use. Our interest is to evaluate second-generation vaccine formulations to identify novel combinations of adjuvants capable of inducing strong, long-lasting immune responses. In this study rhesus monkeys were immunized intramuscularly three times with VMP001 in combination with a stable emulsion (SE) or a synthetic Toll-like receptor 4 (TLR4) agonist (glucopyranosyl lipid A [GLA]) in SE (GLA-SE). Sera and peripheral blood mononuclear cells (PBMCs) were tested for the presence of antigen-specific humoral and cellular responses, respectively. All groups of monkeys generated high titers of anti-P. vivax IgG antibodies, as detected by enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence assays. In addition, all groups generated a cellular immune response characterized by antigen-specific CD4(+) T cells secreting predominantly interleukin-2 (IL-2) and lesser amounts of tumor necrosis factor (TNF). We conclude that the combination of VMP001 and GLA-SE is safe and immunogenic in monkeys and may serve as a potential second-generation vaccine candidate against P. vivax malaria.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910, USA.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lumsden
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
authors.forename: Utaiwan
authors.initials: U
authors.lastname: Srichairatanakul
authors.forename: Kosol
authors.initials: K
authors.lastname: Yongvanitchit
authors.forename: Amporn
authors.initials: A
authors.lastname: Limsalakpetch
authors.forename: Saule
authors.initials: S
authors.lastname: Nurmukhambetova
authors.forename: Jennifer
authors.initials: J
authors.lastname: Klein
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Vedvick
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bennett
authors.forename: Mark E
authors.initials: ME
authors.lastname: Polhemus
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008050:Lipid A / Q000276:immunology; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control*; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D004655:Emulsions; D007074:Immunoglobulin G; D007376:Interleukin-2; D008050:Lipid A; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma