title: Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria.
abstract: Plasmodium vivax is responsible for the majority of malaria cases outside of Africa, and results in substantial morbidity. Transmission blocking vaccines are a potentially powerful component of a multi-faceted public health approach to controlling or eliminating malaria. We report the first phase 1 clinical trial of a P. vivax transmission blocking vaccine in humans. The Pvs25H vaccine is a recombinant protein derived from the Pvs25 surface antigen of P. vivax ookinetes. The protein was expressed in Saccharomyces cerevisiae, purified, and adsorbed onto Alhydrogel. Ten volunteers in each of three dose groups (5, 20, or 80 microg) were vaccinated by intramuscular injection in an open-label study at 0, 28 and 180 days. No vaccine-related serious adverse events were observed. The majority of adverse events causally related to vaccination were mild or moderate in severity. Injection site tenderness was the most commonly observed adverse event. Anti-Pvs25H antibody levels measured by ELISA peaked after the third vaccination. Vaccine-induced antibody is functionally active as evidenced by significant transmission blocking activity in the membrane feeding assay. Correlation between antibody concentration and degree of inhibition was observed. Pvs25H generates transmission blocking immunity in humans against P. vivax demonstrating the potential of this antigen as a component of a transmission blocking vaccine.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Twinbrook 1, Room 1123, Rockville, MD 20852, USA. emalkin@niaid.nih.gov
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Malkin
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: David J
authors.initials: DJ
authors.lastname: Diemert
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Lynn
authors.initials: L
authors.lastname: Lambert
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Miles
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Stowers
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000009:adverse effects / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000009:adverse effects / Q000627:therapeutic use*; D009033:Culicidae / Q000276:immunology / Q000469:parasitology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D017780:Malaria Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016780:Malaria, Vivax / Q000517:prevention & control* / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017780:Malaria Vaccines; C121473:Pvs25 protein, P vivax; D014614:Vaccines, Synthetic