Abstract

The major challenge facing Pfs25- and Pvs25-based transmission blocking vaccine development is to increase the immunogenicity and response longevity. In collaboration with Drs. John Robbins and Rachel Schneerson at the Laboratory of Developmental and Molecular Immunology of the NICHD, we have developed a conjugate vaccine that consists of Pfs25-Pfs25 conjugates. Various conjugation chemistries and methods were evaluated for the highest immunogenicity and most robust conjugation process. The biochemical properties of Pfs25-Pfs25 were characterized and the conjugates were evaluated in animals for their immunogenicity. The immune sera induced by the conjugate vaccine were tested for their ability to block parasite development in mosquitoes. An Investigational New Drug Application has been filed with FDA, intending a Phase 1 trial to test the safety, immunogenicity, and ex-vivo transmission blocking activity in humans.

  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 #
1ZIAAI001007-04
Application #
8157006
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$1,323,730
Indirect Cost

  Institution

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

  Publications

Sagara, Issaka; Healy, Sara A; Assadou, Mahamadoun H et al. (2018) Safety and immunogenicity of Pfs25H-EPA/Alhydrogel, a transmission-blocking vaccine against Plasmodium falciparum: a randomised, double-blind, comparator-controlled, dose-escalation study in healthy Malian adults. Lancet Infect Dis 18:969-982
Nixon, Christian P; Nixon, Christina E; Michelow, Ian C et al. (2018) Antibodies to PfsEGXP, An Early Gametocyte Enriched Phosphoprotein, Predict Decreased Plasmodium falciparum Gametocyte Density In Humans. J Infect Dis :
Assadou, Mahamadoun Hamady; Sagara, Issaka; Healy, Sara A et al. (2017) Malaria Infection and Gametocyte Carriage Rates in Preparation for Transmission Blocking Vaccine Trials in Bancoumana, Mali. Am J Trop Med Hyg 97:183-187
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
Coulibaly, Mamadou B; Gabriel, Erin E; Sinaba, Youssouf et al. (2017) Optimizing Direct Membrane and Direct Skin Feeding Assays for Plasmodium falciparum Transmission-Blocking Vaccine Trials in Bancoumana, Mali. Am J Trop Med Hyg :
MacDonald, Nicholas J; Nguyen, Vu; Shimp, Richard et al. (2016) Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230. J Biol Chem 291:19913-22
Wu, Yimin; Sinden, Robert E; Churcher, Thomas S et al. (2015) Development of malaria transmission-blocking vaccines: from concept to product. Adv Parasitol 89:109-52
Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L et al. (2015) The march toward malaria vaccines. Vaccine 33 Suppl 4:D13-23
Davies, D Huw; Duffy, Patrick; Bodmer, Jean-Luc et al. (2015) Large screen approaches to identify novel malaria vaccine candidates. Vaccine 33:7496-505
Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L et al. (2015) The March Toward Malaria Vaccines. Am J Prev Med 49:S319-33

Showing the most recent 10 out of 13 publications