title: Grammomys surdaster, the Natural Host forPlasmodium bergheiParasites, as a Model to Study Whole-Organism Vaccines Against Malaria.
abstract: AbstractInbred 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 genusGrammomys, the natural hosts forPlasmodium berghei. Thicket rats were acquired and identified asGrammomys surdasterby skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection byP. berghei, and moderately susceptible toPlasmodium yoeliiandPlasmodium chabaudi: 1-2 infected mosquito bites or 25-100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia withP. berghei, and resulted in patent parasitemia withP. yoeliiandP. chabaudistrains 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. UsingP. bergheiANKA radiation-attenuated sporozoites, andP. bergheiANKA andP. yoeliichemoprophylaxis 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.
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Solomon
authors.initials: S
authors.lastname: Conteh
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Lynn
authors.initials: L
authors.lastname: Lambert
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Sachy
authors.initials: S
authors.lastname: Orr-Gonzalez
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Herrod
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Yvette L
authors.initials: YL
authors.lastname: Robbins
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Dariyen
authors.initials: D
authors.lastname: Carter
authors.affiliation: Department of Parasitology, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo.
authors.forename: Stomy Bin Shamamba
authors.initials: SBS
authors.lastname: Karhemere
authors.affiliation: Department of Parasitology, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo.
authors.forename: Pati
authors.initials: P
authors.lastname: Pyana
authors.affiliation: Department of Biomedical Sciences, Unit of Parasite Diagnostics, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Büscher
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology (LMIV), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D051189:Murinae / Q000469:parasitology*; D010962:Plasmodium berghei / Q000502:physiology*
chemical_list: D017780:Malaria Vaccines