title: Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya.
abstract: It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.
authors.affiliation: Clinical Research Centre, Nairobi, Kenya.
authors.forename: J A
authors.initials: JA
authors.lastname: Sherwood
authors.forename: R S
authors.initials: RS
authors.lastname: Copeland
authors.forename: K A
authors.initials: KA
authors.lastname: Taylor
authors.forename: K
authors.initials: K
authors.lastname: Abok
authors.forename: A J
authors.initials: AJ
authors.lastname: Oloo
authors.forename: J B
authors.initials: JB
authors.lastname: Were
authors.forename: G T
authors.initials: GT
authors.lastname: Strickland
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: J D
authors.initials: JD
authors.lastname: Bales
authors.forename: R A
authors.initials: RA
authors.lastname: Wirtz
authors.forename: J
authors.initials: J
authors.lastname: Wittes
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: J U
authors.initials: JU
authors.lastname: Que
authors.forename: S J
authors.initials: SJ
authors.lastname: Cryz
authors.forename: C N
authors.initials: CN
authors.lastname: Oster
authors.forename: C R
authors.initials: CR
authors.lastname: Roberts
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000962:Antimalarials / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D007111:Immunity, Cellular; D007303:Insect Vectors; D007630:Kenya / Q000453:epidemiology; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D017780:Malaria Vaccines