Blood Stage Malaria Vaccine Eliciting High Antigen-Specific Antibody Concentrations Confers No Protection to Young Children in Western Kenya

Abstract

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

Evaluation of Recurrent Parasitemia after Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Children in Western Kenya

“…5 AL was administered in a manner consistent with public-health practices (i.e., the first dose was given in the clinic, and the remainder was given to the parent or guardian for administration at home). However, active and passive case detection for subsequent malaria was intense and prolonged.…”

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

“…To date, research in this field has focused on a few protein candidates including merozoite surface protein (MSP)-1 (14), MSP-2 (8), MSP-3 (15)(16)(17)(18), apical membrane Ag 1 (AMA-1) (19), erythrocyte binding Ag 175 (EBA-175) (20), glutamate-rich protein (GLURP) (15,21), and serine repeat Ag 5 (SERA5) (22). These Ags are all merozoite proteins, either located on the merozoite surface or contained within apical invasion organelles.…”

Immunogenicity of the Merozoite Surface Protein-1 (Msp-1) of Human Plasmodium Sp.

“…Another Phase I trial was conducted in 135 Kenyan children of ages 12 years to 47 months, and the induced-immune response was dosage-dependent (68). However, a Phase II trial with 400 Kenyan children indicated that FMP1/AS02A may not be a promising candidate for monovalent malaria vaccine, with an overall vaccine efficacy of 5.1% only (69).…”