Pattern of antibody responses to Plasmodium falciparum antigens in individuals differentially exposed to Anopheles bites

Abstract

Background: In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. The consequences on pathogen-specific immune responses are not well known. This study evaluated and compared the humoral responses specific to merozoite stage vaccine candidates of Plasmodium falciparum, in children differentially exposed to Anopheles bites in a natural setting. Methods:The cross-sectional study was carried out in Bouaké (Côte d'Ivoire) where entomological data and blood samples from children (0-14 years) were collected in two sites with similar malaria prevalence. Antibody (IgG, IgG1, IgG3) responses to PfAMA1 and PfMSP1 were evaluated by ELISA. Univariate and multivariate analysis were performed to assess the relationship between the immune responses to P. falciparum antigens and exposure to Anopheles bites in the total cohort and in each site, separately. The individual level of exposure to Anopheles bites was evaluated by quantifying specific IgG response to the Anopheles gSG6-P1 salivary peptide, which represents a proxy of Anopheles exposure.

Influence of Host-Related Factors and Exposure to Mosquito Bites on the Dynamics of Antibody Response to Plasmodium falciparum Antigens

“…In the present study, we showed that Aedes exposure was negatively associated with the anti- Pf GLURP-R0 immune response, whereas it was positively associated with the anti- Pf Schz IgG response. The epidemiological observation for the down-regulated IgG response to Pf GLURP-R0 in individuals with higher exposure is consistent with previous studies that reported a down-regulated immune response to a specific antigen in hosts exposed to arthropod saliva compared with naive vertebrate hosts [ 21 , 32 , 33 ]. Schizonts comprise a set of antigens with varying immunogenicity, while Pf GLURP-R0 is a unique antigen at the surface of infected erythrocytes.…”

“…The exposure to Aedes bites was associated with the evolution of IgG response to Pf Schz and Pf GLURP-R0, while Anopheles exposure was not found to modulate anti- Plasmodium immunity in the 6-week follow-up period. It is increasingly recognized that the immune modulatory properties of mosquito saliva act both on the innate and adaptive immune responses of the vertebrate host, but only a few studies have assessed the consequences of Plasmodium immune responses in a natural population [ 14 , 32 , 33 , 65 ]. These studies investigated the immune relationship within a homologous malaria context ( Anopheles – Plasmodium ), while in the present study, we observed different anti- Plasmodium immunity modulation according to the mosquito genus with a significant effect of Aedes exposure.…”

“…The study was conducted in Dar-es-Salam, a neighborhood of Bouaké city located in the center of Côte d’Ivoire, from April to June 2016. The local climate and malaria epidemiology have been previously described [ 33 , 41 ]. The area has intense malaria transmission and P .…”

“…Serology testing of human exposure to mosquito salivary antigens (Nterm–34 kDa and gSG6-P1) was carried out by ELISA as described in [ 33 ] but with some modifications. Sera were incubated in duplicate wells at 4 °C overnight at a dilution of 1/40 in 0.1% PBST, mouse biotinylated Ab to human IgG (BD Pharmingen, San Diego CA, USA) was incubated at a dilution of 1/2000 in 1% PBST, and streptavidin biotin peroxidase was then added (1/1000; 1 h at 37 °C).…”

“…A difference in the cytophilic Ab response to Plasmodium according to the intensity of exposure to Anopheles bites was reported, with a down-regulated IgG1 level seen in children with higher exposure, while IgG3 levels were similar in children with low or high exposure to Anopheles bites [ 32 ]. More recently, a study suggested that, in addition to other factors, Anopheles saliva may also down-modulate the anti- Pf MSP1 IgG, IgG1, and IgG3 immunity [ 33 ].…”