Abstract

The major discovery this year are as follows. 1. Initiated a phase I clinical trial assessing whether irradiated PfSPZ given by the IV or IM route is safe, and confers durable immunity and protection using various doses and intervals for immunization. 2. Characterized the sporozoite specific T cell and NK responses longitudinally following vaccination and infection to provide insights into the correlates of protection. Used Fluidigm to characterize the heterogeneity of the sporozoite specific CD4+ T cell response in vaccinated/protected versus vaccinated/unprotected or control infected subjects. 3. Isolated monoclonal antibodies against malaria specific proteins ( eg CSP) in vaccinated and protected subjects. 4. Showed that high-level durable protection can be induced up to 1 year after immunization. 5. Defined immune correlates of protection. 6. Showed that high-level durable protection against heterologous challenge can be induced with a 3 dose vaccine regimen.

  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 #
1ZIAAI005107-07
Application #
9351997
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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State
Country
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  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

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