Abstract

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. Initiated studies of nonhuman primate models of pre-erythrocytic malaria immunity, using whole organism and subunit vaccine strategies 2. Identified an additional panel of candidate pre-erythrocytic antigens that should be assessed in mluse models 3. Determined that naturally exposed African children develop CD8 T cell interferon gamma responses against leading PEVA antigens 4. Established an in vitro imaging system to visualize T cell killing of infected hepatocytes

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001135-02
Application #
8336344
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2011
Total Cost
$691,420
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Pichugin, Alexander; Zarling, Stasya; Perazzo, Leah et al. (2018) Identification of a Novel CD8 T Cell Epitope Derived from Plasmodium berghei Protective Liver-Stage Antigen. Front Immunol 9:91
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
Coelho, Camila Henriques; Doritchamou, Justin Yai Alamou; Zaidi, Irfan et al. (2017) Advances in malaria vaccine development: report from the 2017 malaria vaccine symposium. NPJ Vaccines 2:34
Zaidi, Irfan; Diallo, Hama; Conteh, Solomon et al. (2017) ?? T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations. J Immunol 199:3781-3788
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

Showing the most recent 10 out of 21 publications