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BackgroundThe human host elicits specific immune responses after exposure to various life stages of the malaria parasite as well as components of mosquito saliva injected into the host during a mosquito bite. This study describes differences in IgG responses against antigens derived from the sporozoite (PfCSP), asexual stage parasite (PfEBA175) and the gametocyte (Pfs230) in addition to anAnopheles gambiaesalivary gland antigen (gSG6-P1) in two communities in Ghana with similar blood stage malaria parasite prevalence.MethodologyThis study used archived plasma samples collected from an earlier cross-sectional study that enrolled volunteers aged from 6 months to 70 years from Simiw, peri-urban community (N=347) and Obom, rural community (N=291). An archived thick and thin blood smear for microscopy was used for the estimation ofPlasmodiumparasite density and species and DNA extraction from blood spots andP. falciparumconfirmation was performed using PCR. This study used the stored plasma samples to determine IgG antibody levels toPlasmodium falciparumandAnophelessalivary antigens using indirect ELISA.ResultsIndividuals from Simiw had significantly higher levels of IgG against mosquito gSG6-P1 (median (95%CI)) (2.590 (2.452-2.783) ng/mL) compared to those from Obom (2.119 (1.957-2.345) ng/mL), p0.05).ConclusionIn conclusion, malaria transmission dynamics is highly complex. The similar malaria transmission intensity identified in the two communities resulted from a different combination of vector, environmental and host factors. With one community likely having a higher prevalence of uninfected mosquitoes and the other a larger reservoir of gametocyte carriers.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum parasite. Using protein microarrays, levels of IgG to 1,000 P. falciparum antigens were measured in 2,138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase 3 trial, sampled before and at four longitudinal visits after vaccination. One month post-vaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no pre-vaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (∼11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and re-increasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site and post-vaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.