1921
Volume 96, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

Inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. To establish a more rigorous animal model, we acquired African woodland thicket rats of the genus , the natural hosts for . Thicket rats were acquired and identified as by skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection by , and moderately susceptible to and : 1–2 infected mosquito bites or 25–100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia with , and resulted in patent parasitemia with and strains for at least 50% of animals. We then assessed efficacy of whole-organism vaccines to induce sterile immunity, and compared the thicket rat model to conventional mouse models. Using ANKA radiation-attenuated sporozoites, and ANKA and chemoprophylaxis vaccination approaches, we found that standard doses of vaccine sufficient to protect laboratory mice for a long duration against malaria challenge, are insufficient to protect thicket rats, which require higher doses of vaccine to achieve even short-term sterile immunity. Thicket rats may offer a more stringent and pertinent model for evaluating whole-organism vaccines.

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  • Received : 12 Sep 2016
  • Accepted : 29 Nov 2016

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