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FN1Financial support: This research was supported and funded by the Intramural Research Program of the National Institute for Allergy and Infectious Disease of the National Institutes of Health.
FN2Authors' addresses: Solomon Conteh, Charles Anderson, Lynn Lambert, Sachy Orr-Gonzalez, Jessica Herrod, Yvette L. Robbins, Dariyen Carter, and Patrick E. Duffy, Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD, E-mails: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, and email@example.com. Stomy Bin Shamamba Karhemere and Pati Pyana, Department of Parasitology, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo, E-mails: firstname.lastname@example.org and email@example.com. Philippe Büscher, Department of Biomedical Sciences, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium, E-mail: firstname.lastname@example.org.
- The American Society of Tropical Medicine and Hygiene
- Source: The American Journal of Tropical Medicine and Hygiene, Volume 96, Issue 4, Apr 2017, p. 835 - 841
Grammomys surdaster, the Natural Host for Plasmodium berghei Parasites, as a Model to Study Whole-Organism Vaccines Against Malaria
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 Grammomys, the natural hosts for Plasmodium berghei. Thicket rats were acquired and identified as Grammomys surdaster by skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection by P. berghei, and moderately susceptible to Plasmodium yoelii and Plasmodium chabaudi: 1–2 infected mosquito bites or 25–100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia with P. berghei, and resulted in patent parasitemia with P. yoelii and P. chabaudi 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 P. berghei ANKA radiation-attenuated sporozoites, and P. berghei ANKA and P. yoelii 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.