1921
image of Grammomys surdaster, the Natural Host for Plasmodium berghei Parasites, as a Model to Study Whole-Organism Vaccines against Malaria
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
USD

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 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.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.16-0745
2017-01-23
2017-03-29
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.16-0745
Loading
  • Published online : 23 Jan 2017
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error