Abstract
Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system. In the current study, a squalene based adjuvant (AddaVax, InvivoGen, San Diego, Ca) equivalent to the clinically approved MF59 (Seqiris, Maidenhead, UK) elicited greater antibody responses in mice than the previously employed adjuvant polyinosinic:polycytidylic acid, ((poly(I:C), InvivoGen, San Diego, Ca) and the clinically approved Aluminum hydroxide gel (Alum, Invivogen, San Diego, Ca) adjuvant. Use of the AddaVax adjuvant also expanded the range of IgG subtypes elicited by mouse vaccination. Sera passively transferred into mice from MCSP/AddaVax immunized 1 and 6 month old macaques significantly reduced liver sporozoite load upon sporozoite challenge. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization. The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population.
Highlights
Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection
We have previously reported on the protective efficacy in a mouse challenge model of a vaccine platform that fused the chemokine macrophage inflammatory protein 3α (MIP3α), known as Chemokine (C–C Motif) Ligand 20 (CCL20), to a slightly truncated version of the circumsporozoite protein of the Plasmodium falciparum parasite (PfCSP)
We have examined in C57Bl/6 mice and infant and juvenile Rhesus macaques the immunogenicity of a malaria vaccine platform that had previously demonstrated, using a different adjuvant, extended protection efficacy in a murine malaria challenge system
Summary
Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population. There have been reports that prolonging the interval between primary and booster immunizations, as well as reducing the vaccine dose used in secondary immunizations, may provide a strategy for extending protection with the RTS,S malaria vaccine that has undergone advanced testing in clinical t rials[11,13,14] These strategies have not addressed the finding that young infants respond poorly to this v accine[11,12,15]. Protection sustained over that period of time post final immunization had not previously been reported in malaria mouse challenge models
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