Rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes

Malaria Journal

Research

Philippe Saudan¹  Nathan A. Hoyt²  Anthony D. May²  Norman C. Waters³  Timothy W. Phares⁴  Christopher J. Genito⁴  Sheetij Dutta⁴  Farhat A. Khan⁴  Michael D. Porter⁴  Margot DeBot⁴ 

[1] Cytos Biotechnology, Wagistrasse 25, 8952, Schlieren, Switzerland;Division of Veterinary Medicine, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;Malaria Vaccine Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;Structural Vaccinology Laboratory, Malaria Vaccine Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;

关键词: Circumsporozoite protein;    Vaccine;    Mice;    Rhesus;    Macaque;    Malaria;   

DOI  :  10.1186/s12936-017-1766-3

 received in 2016-12-30, accepted in 2017-02-28,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNon-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic.MethodsA comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted Plasmodium falciparum circumsporozoite protein (CSP)-based vaccines was conducted in mouse and rhesus models. One vaccine was a soluble recombinant protein (CSP) and the other was the same CSP covalently conjugated to the Qβ phage particle (Qβ-CSP).ResultsMice showed different kinetics of antibody responses and different sensitivity to the NANP-repeat and N-terminal epitopes as compared to rhesus. While mice failed to discern differences between the protective efficacy of CSP versus Qβ-CSP vaccine following direct challenge with transgenic Plasmodium berghei parasites, rhesus serum from the Qβ-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity.ConclusionsDespite some immunologic parallels between models, these data demonstrate that differences between the immune responses induced in the two models risk conflicting decisions regarding potential vaccine utility in humans. In combination with historical observations, the data presented here suggest that although murine models may be useful for some purposes, non-human primate models may be more likely to predict the human response to investigational vaccines.

【 授权许可】

CC BY   
© The Author(s) 2017