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BackgroundNaturally acquired immunity to malaria may involve different immune mechanisms working in concert, however, their respective contributions and potential antigenic targets have not been clearly established. Here, we assessed the roles of opsonic phagocytosis and antibody-mediated merozoite growth inhibition in Plasmodium falciparum (P. falciparum) infection outcomes in Ghanaian children.MethodsThe levels of merozoite opsonic phagocytosis, growth inhibition activities and six P. falciparum antigen-specific IgG of plasma samples from children (n=238, aged 0.5 to 13 years) were measured at baseline prior to the malaria seasons in southern Ghana. The children were then actively and passively followed up for febrile malaria and asymptomatic P. falciparum infection detection in a 50-week longitudinal cohort. P. falciparum infection outcome was modelled as a function of the measured immune parameters while accounting for important demographic factors.ResultsHigh plasma activity of opsonic phagocytosis [adjusted odds ratio (aOR)= 0.16; 95%CI= 0.05 - 0.50, p = 0.002], and growth inhibition (aOR=0.15; 95% CI = 0.04-0.47; p = 0.001) were individually associated with protection against febrile malaria. There was no evidence of correlation (b= 0.13; 95% CI= -0.04-0.30; p=0.14) between the two assays. IgG antibodies against MSPDBL1 correlated with opsonic phagocytosis (OP) while IgG against PfRh2a correlated with growth inhibition. Notably, IgG antibodies against RON4 correlated with both assays.ConclusionOpsonic phagocytosis and growth inhibition are protective immune mechanisms against malaria that may be acting independently to confer overall protection. Vaccines incorporating RON4 may benefit from both immune mechanisms.

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.

Abstract Background Malaria remains an important health problem in India with approximately 1 million cases in 2014. Of these, 7% occurred in the Jharkhand state mainly in the tribal population. Methods This study was conducted in Dumargarhi, a tribal village about 42 km east of Ranchi city, Jharkhand, from May 2014 to September 2016. Four point prevalence surveys were carried out during consecutive high (October–December) and low (June–August) transmission seasons. Malaria cases were recorded from April 2015 to April 2016 through fortnightly visits to the village. Adult mosquito densities were monitored fortnightly by manual catching using suction tube method. Results The study area consists of five hamlets inhabited by 945 individuals living in 164 households as recorded through a house-to-house census survey performed at enrollment. The study population consisted predominantly of the Munda (n = 425, 45%) and Oraon (n = 217, 23%) ethnic groups. Study participants were categorized as per their age 0–5, 6–10, 11–15 and >15 years. There were 99 cases of clinical malaria from April 2015 to April 2016 and all malaria cases confirmed by microscopy were attributed to Plasmodium falciparum (94 cases) and Plasmodium vivax (5 cases), respectively. During the high transmission season the mean density of P. falciparum parasitaemia per age group increased to a peak level of 23,601 parasites/μl in the 6–10 years age group and gradually declined in the adult population. Malaria attack rates, parasite prevalence and density levels in the study population showed a gradual decrease with increasing age. This finding is consistent with the phenomenon of naturally acquired immunity against malaria. Three vector species were detected: Anopheles fluviatilis, Anopheles annularis, and Anopheles culicifacies. The incoherence or complete out of phase pattern of the vector density peaks together with a high prevalence of parasite positive individuals in the study population explains the year-round malaria transmission in the study region. Conclusions The collection of clinical data from a well-characterized tribal cohort from Jharkhand, India, has provided evidence for naturally acquired immunity against malaria in this hyperendemic region. The study also suggests that enforcement of existing control programmes can reduce the malaria burden further.