title: Safety, immunogenicity and limited efficacy study of a recombinant Plasmodium falciparum circumsporozoite vaccine in Thai soldiers.
abstract: Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinees. Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p = 0.005) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether high levels of CS antibody are protective remains to be resolved.
authors.affiliation: Armed Forces Research Institute for Medical Sciences (AFRIMS), Bangkok, Thailand.
authors.forename: A E
authors.initials: AE
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Singharaj
authors.forename: H K
authors.initials: HK
authors.lastname: Webster
authors.forename: J
authors.initials: J
authors.lastname: Pipithkul
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: J W
authors.initials: JW
authors.lastname: Boslego
authors.forename: K
authors.initials: K
authors.lastname: Krinchai
authors.forename: P
authors.initials: P
authors.lastname: Su-archawaratana
authors.forename: C
authors.initials: C
authors.lastname: Wongsrichanalai
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D004311:Double-Blind Method; D006801:Humans; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines; D012449:Safety; D013785:Thailand
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C041595:circumsporozoite protein, Protozoan