GMZ2 Vaccine-Induced Antibody Responses, Naturally Acquired Immunity and the Incidence of Malaria in Burkinabe Children.

GMZ2 is a malaria vaccine candidate evaluated in a phase 2b multi-centre trial. Here we assessed antibody responses and the association of naturally acquired immunity with incidence of malaria in one of the trial sites, Banfora in Burkina Faso. The analysis included 453 (GMZ2 = 230, rabies = 223) children aged 12-60 months old. Children were followed-up for clinical malaria episodes for 12 months after final vaccine administration. Antibody levels against GMZ2 and eleven non-GMZ2 antigens were measured on days 0 and 84 (one month after final vaccine dose). Vaccine efficacy (VE) differed by age group (interaction, (12-35 months compared to 36-60 months), p = 0.0615). During the twelve months of follow-up, VE was 1% (95% confidence interval [CI] -17%, 17%) and 23% ([CI] 3%, 40%) in the 12 - 35 and 36 - 60 months old children, respectively. In the GMZ2 group, day 84 anti-GMZ2 IgG levels were associated with reduced incidence of febrile malaria during the follow up periods of 1-6 months (hazard ratio (HR) = 0.87, 95%CI = (0.77, 0.98)) and 7-12 months (HR = 0.84, 95%CI = (0.71, 0.98)) in the 36-60 months old but not in 12-35 months old children. Multivariate analysis involving day 84 IgG levels to eleven non-vaccine antigens, identified MSP3-K1 and GLURP-R2 to be associated with reduced incidence of malaria during the 12 months of follow up. The inclusion of these antigens might improve GMZ2 vaccine efficacy.

Evidence that seasonal malaria chemoprevention with SPAQ influences blood and pre-erythrocytic stage antibody responses of Plasmodium falciparum infections in Niger.

BACKGROUND: In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. METHODS: This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. RESULTS: The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001). CONCLUSION: The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.