Development of Pre-Erythrocytic Malaria Vaccines

Seder, Robert A.

Abstract

The major discovery this year are as follows. 1. Showed that radiation attenuated sporozoites administered intravenously into NHP induced potent CD4 and CD8+ T cell responses in blood and liver. Established that a high frequency of NK cells in the liver secrete IFN-g in response to stimulation providing an additional effector cell for protection. Furthermore, showed that monocytes and dendritic cells present SPZ antigen to T cells. 2. Completed a phase I clinical trial assessing whether irradiated PfSPZ given by the IV route is safe and protective in a dose escalation study. 3. Showed that an attenuated malaria vaccine ( PfSPZ Vaccine) confers high level protection in humans following an experimental challenge with malaria infection. 4. Showed that the dose of the PfSPZ Vaccine is critical for mediating immunity and protection.

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 #: 1ZIAAI005107-04
• Application #: 8745642
• Support Year: 4
• Fiscal Year: 2013
• Total Cost: $210,038

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Jongo, Said A; Shekalaghe, Seif A; Church, L W Preston et al. (2018) Safety, Immunogenicity, and Protective Efficacy against Controlled Human Malaria Infection of Plasmodium falciparum Sporozoite Vaccine in Tanzanian Adults. Am J Trop Med Hyg 99:338-349

Kisalu, Neville K; Idris, Azza H; Weidle, Connor et al. (2018) A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med 24:408-416

Draper, Simon J; Sack, Brandon K; King, C Richter et al. (2018) Malaria Vaccines: Recent Advances and New Horizons. Cell Host Microbe 24:43-56

Mordmüller, Benjamin; Surat, Güzin; Lagler, Heimo et al. (2017) Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature 542:445-449

Lyke, Kirsten E; Ishizuka, Andrew S; Berry, Andrea A et al. (2017) Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection. Proc Natl Acad Sci U S A 114:2711-2716

Sack, Brandon K; Mikolajczak, Sebastian A; Fishbaugher, Matthew et al. (2017) Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice. NPJ Vaccines 2:27

Ishizuka, Andrew S; Lyke, Kirsten E; DeZure, Adam et al. (2016) Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med 22:614-23

Seder, Robert A; Chang, Lee-Jah; Enama, Mary E et al. (2013) Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341:1359-65

Kastenmuller, Kathrin; Espinosa, Diego A; Trager, Lauren et al. (2013) Full-length Plasmodium falciparum circumsporozoite protein administered with long-chain poly(IýýC) or the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice. Infect Immun 81:789-800

Epstein, J E; Tewari, K; Lyke, K E et al. (2011) Live attenuated malaria vaccine designed to protect through hepatic CD8ýýý T cell immunity. Science 334:475-80