Pre-erythrocytic vaccine antigen (PEVA) candidates are transcribed during liver stage (LS) development. PEVA immunogens are recognized by CD8+ and CD4+ T cells in protected rodents and naturally exposed humans. The LMIV Pathogenesis and Immunity Section and SBRI have assessed the protective efficacy of some of these immunogens after DNA vaccination in rodent models of malaria. Our next objective is to establish the nonhuman primate and human models of protective pre-erythocytic immunity for further studies, to identify additional antigens that may be contributing to protective pre-erythrocytic immunity, and to assess the efficacy of leading immunogens in animals models that can guide the prioritization of those antigens to be tested in humans. During the past fiscal year, LMIV scientists have accomplished the following: 1. Completed pilot studies of nonhuman primate models of pre-erythrocytic malaria immunity, using whole organism and subunit vaccine strategies. We have determined that rhesus monkeys can be protected against P. knowlesi infection by whole organism vaccination, and also that CD8 T cell responses against 2 of our novel PEVA antigens are associated with reduced blood stage burden of malaria after sporozoite challenge. 2. Identified 2 additional candidate pre-erythrocytic antigens that confer protection against liver stage malaria in rodent models. 3. Determined that naturally exposed African children who develop CD8 T cell interferon gamma responses against leading PEVA antigens, demonstrate reduced risk of malaria infection during followup. This observation is being confirmed in another season of followup. 4. Established a flow cytometry based method to measure the effect of antibodies to block malaria parasites from infecting liver cells.

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Nash, Scott D; Prevots, D Rebecca; Kabyemela, Edward et al. (2017) A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth Cohort Exposed to Intense Malaria Transmission. Am J Trop Med Hyg 96:1190-1196
Conteh, Solomon; Anderson, Charles; Lambert, Lynn et al. (2017) Grammomys surdaster, the Natural Host for Plasmodium berghei Parasites, as a Model to Study Whole-Organism Vaccines Against Malaria. Am J Trop Med Hyg 96:835-841
Hobbs, Charlotte V; Anderson, Charles; Neal, Jillian et al. (2017) Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge. J Infect Dis 215:122-130
Sissoko, Mahamadou S; Healy, Sara A; Katile, Abdoulaye et al. (2017) Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis 17:498-509
Speake, Cate; Pichugin, Alexander; Sahu, Tejram et al. (2016) Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein. PLoS One 11:e0159449
Herrera, Raul; Anderson, Charles; Kumar, Krishan et al. (2015) Reversible conformational change in the Plasmodium falciparum circumsporozoite protein masks its adhesion domains. Infect Immun :
Sahu, Tejram; Lambert, Lynn; Herrod, Jessica et al. (2015) Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model. Front Microbiol 6:283
Davies, D Huw; Duffy, Patrick; Bodmer, Jean-Luc et al. (2015) Large screen approaches to identify novel malaria vaccine candidates. Vaccine 33:7496-505
Murphy, Jittawadee R; Weiss, Walter R; Fryauff, David et al. (2014) Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies. Malar J 13:215
Talley, Angela K; Healy, Sara A; Finney, Olivia C et al. (2014) Safety and comparability of controlled human Plasmodium falciparum infection by mosquito bite in malaria-naïve subjects at a new facility for sporozoite challenge. PLoS One 9:e109654

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