Abstract

The major discovery this year are as follows. 1. Completed a phase II clinical trial in Kenya in 5-12 month infants to assess whether irradiated PfSPZ given by the IV route is safe, and confers durable immunity and protection against natural exposure. Immune responses are currently being assessed to understand why the vaccine had limited protection in this age group. 2. Isolated monoclonal antibodies against malaria specific proteins ( eg CSP) in vaccinated and protected subjects. Showed these antibodies were protective in vivo in two different mouse models. Defined a novel epitope on PfCSP which is the site of neutralization. A crystal structure of a human antibody was obtained binding to a specific and unique epitope on PfCSP. The data provide an antibody that can be advanced for prevention of malaria in humans and defines a novel site of vulnerability on PfCSP that can be advanced as a vaccine using structure based vaccine design. 3. Started a clinical development plan for mAB CIS 43 against the junctional region of CSP for testing in humans. 4. Defined a new human mAb with distinct specificity and increased potency compared to CIS 43. 5. Comparative analysis of the in vivo potency of a number of human mAbs against CSP. Elucidation of the in vivo mechanisms of these antibodies focused in skin and liver.

  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 #
1ZIAAI005107-10
Application #
10019257
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2019
Total Cost
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

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