title: Use of the rhesus monkey as an experimental model to test the degree of efficacy of an anti-sporozoite peptide malaria vaccine candidate combined with copolymer-based adjuvants.
abstract: Humoral response against sporozoites is not effective in protecting individuals from getting malaria. Reduction in the infectivity of sporozoites has not been quantified for most anti-sporozoite vaccines tested. Quantification requires animal models providing predictable prepatent periods, e.g., time elapsed between sporozoite inoculation and detection of parasitemia, to be used as an indicator of activity against sporozoites. A delay in prepatent period from vaccinated animals would therefore reflect a protective effect in reducing the number of parasites. We report the vaccination of rhesus monkeys with a synthetic peptide reproducing part of the repeated region of the circumsporozoite protein of Plasmodium cynomolgi. This peptide was conjugated to the carrier protein diphtheria toxoid and injected with four adjuvant formulations that differed only by the type of emulsion or immunomodulator. Because all five control animals had a synchronous prepatent period after challenge with live sporozoites, it was possible to quantify the protective efficacy for each vaccine formulation, even though all monkeys developed parasitemia. Sporozoite elimination correlated with the immunomodulator and the type of emulsion. Such elimination was related neither to antibody titer against the immunizing peptide or the whole sporozoite, nor to antibody isotype induced by the vaccine formulation.
authors.affiliation: Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: P
authors.initials: P
authors.lastname: Millet
authors.forename: K K
authors.initials: KK
authors.lastname: Grady
authors.forename: M
authors.initials: M
authors.lastname: Olsen
authors.forename: G G
authors.initials: GG
authors.lastname: Galland
authors.forename: J S
authors.initials: JS
authors.lastname: Sullivan
authors.forename: C L
authors.initials: CL
authors.lastname: Morris
authors.forename: B B
authors.initials: BB
authors.lastname: Richardson
authors.forename: W E
authors.initials: WE
authors.lastname: Collins
authors.forename: R L
authors.initials: RL
authors.lastname: Hunter
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008253:Macaca mulatta; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000009:adverse effects; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D016789:Plasmodium cynomolgi / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan