ObjectiveThe antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children.MethodsA randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12–47 months in general good health.Children were randomised in a 1∶1 fashion to receive either FMP1/AS02 (50 µg) or Rabipur® rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature ≥37.5°C with asexual parasitaemia of ≥50,000 parasites/µL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations.Results374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-142 antibody concentrations increased from1.3 µg/mL to 27.3 µg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: −26% to +28%; p-value = 0.7).ConclusionsFMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-142 vaccine development should focus on other formulations and antigen constructs.Trial RegistrationClinicaltrials.gov NCT00223990

randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya" (2007 AbstractWe report the first trial of candidate malaria vaccine antigen FMP1, a 42 kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax ® rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax ® group This document is a U.S. government work and is not subject to copyright in the United States. J. A. Stoute et al. / Vaccine 25 (2007) 176-184 177 (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1 42 (F 1,335 = 13.16; P < 0.001) and the Day 90 responses to MSP-1 42 (F 1,335 = 16.69; P < 0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria. Published by Elsevier Ltd.

BackgroundThe existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-119 IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission.MethodsTotal IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5–14 and ≥ 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-119 specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-119 seroprevalence and parasite prevalence.ResultSeroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ2 = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-119 antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the equivalent gSG6-P1 seroprevalence were 28%, 34% and 54%, respectively.ConclusionThe seroprevalence of IgG to gSG6-P1 was sensitive and robust in distinguishing between hypo, meso and hyper transmission settings and seasonal fluctuations.