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

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Ngôn ngữ: eng

Ký hiệu phân loại: 616.9 Other diseases

Thông tin xuất bản: Oak Ridge, Tenn. : Oak Ridge, Tenn. : Oak Ridge Institute for Science and Education ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2017

Mô tả vật lý: Size: Article No. 115 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 260595

 Background: Non-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 <
 em>
 Plasmodium<
 /em>
  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. Methods: A comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted <
 em>
 Plasmodium falciparum<
 /em>
  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 Q? phage particle (Q?-CSP). Results: Mice 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 Q?-CSP vaccine following direct challenge with transgenic <
 em>
 Plasmodium berghei<
 /em>
  parasites, rhesus serum from the Q?-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity. Conclusions: Despite 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.
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