Evaluation of Novel PE Malaria Vaccine Candidates with Recombinant Adenoviruses

Duffy, Patrick

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 these immunogens after DNA vaccination in rodent models of malaria. Our next objective is to test the protective efficacy of these immunogens in non-human primates. Adenoviruses can infect dividing and non-dividing cells, express high levels of exogenous genes, and induce potent cellular and antibody responses. Human adenoviruses 5 (Ad5), in particular, have consistently proven a versatile tool to generate CD8+ T cells in various animal models. Furthermore, recombinant human Ad5 vectors can be generated with ease using commercially available kits.

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 #: 1ZIAAI001135-01
• Application #: 8157113
• Support Year: 1
• Fiscal Year: 2010
• Total Cost: $323,529

Institution

• Name: National Institute of Allergy and Infectious Diseases

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