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. Demonstrated that a novel full length P. falciparum CSP protein elicited potent CD4+ T cell and humoral immunity in mice sufficient to limit parasite replication in vivo following challenge. 3. Initiated a phase I clinical trial assessing whether irradiated PfSPZ given by the IV route is safe and protective in a dose escalation study.

  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 #
1ZIAAI005107-03
Application #
8556123
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$210,038
Indirect Cost

  Institution

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

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

Showing the most recent 10 out of 11 publications