The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections

Abstract

Individuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificity of gametocyte-induced antibody responses. In this study, we assessed antibody responses in participants of two controlled human malaria infection (CHMI) studies by ELISA, multiplexed bead-based antibody assays and protein microarray. By comparing antibody responses in participants with and without gametocyte exposure, we aimed to disentangle the antibody response induced by asexual and sexual stage parasites. We showed that after a single malaria infection, a significant anti-sexual stage humoral response is induced in malaria-naïve individuals, even after exposure to relatively low gametocyte densities (up to ~1,600 gametocytes/mL). In contrast to antibody responses to well-characterised asexual blood stage antigens that were detectable by day 21 after infection, responses to sexual stage antigens (including transmission blocking vaccine candidates Pfs48/45 and Pfs230) were only apparent at 51 days after infection. We found antigens previously associated with early gametocyte or anti-gamete immunity were highly represented among responses linked with gametocyte exposure. Our data provide detailed insights on the induction and kinetics of antibody responses to gametocytes and identify novel antigens that elicit antibody responses exclusively in individuals with gametocyte exposure. Our findings provide target identification for serological assays for surveillance of the malaria infectious reservoir, and support vaccine development by describing the antibody response to leading vaccine antigens after primary infection.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial

“…Presence of biomarkers for correlates of infection and infectivity (ie, proteins associated with inflammation) or parasite density (HRP2). 42 …”

“…42 ► Antibody responses to gametocyte and asexual stage proteins in established multiplex platforms. 42 Antigens will include but not be restricted to Pfs230, Pfs48/45 for sexual stage proteins to assess the influence on transmission to mosquitoes and PfAMA, PfMSP-1 and PfETRAMP-5 to assess the effect of interventions on the development of humoral immunity.…”

Advances in Microfluidics for Single Red Blood Cell Analysis

“…Furthermore, the IR laser capabilites to form a bubble to displace trapped cell/particle Deformability analysis of RBCs using micro-capillaries has shown experimental observations based on the RBC dynamics to detect cellular subpopulations [171]. Other prospective studies include, RBC shape assessment [313], malaria screening [314][315][316][317][318], analysis of microcapillary occlusionsickle cell disease [319][320][321][322], sickle cell disease [323,324], detection and labeling of lymphoma cells [325], blood grouping and phenotyping [326,327], and the study of dispersive RBCs flowing through microchannels [328].…”

Target-agnostic identification of human antibodies toPlasmodium falciparumsexual forms reveals cross stage recognition of glutamate-rich repeats

“…Microarray design and protocol have been extensively detailed in (29) and (72) . Briefly, selection proteins to be printed on the array was made on the basis of a systematic analyses of proteomic data by Meerstein-Kessel et al (73).…”

“…Briefly, selection proteins to be printed on the array was made on the basis of a systematic analyses of proteomic data by Meerstein-Kessel et al (73). In total 943 protein targets representing 528 unique gene IDs were expressed for the array using an in vitro transcription translation system; these were printed onto nitrocellulose coated slides at the University of California, Irvine as described previously (72). Microarray slides were rehydrated in blocking buffer (GVS #10485356) while B1E11K was diluted 1:100 in a 20% E. coli lysate/blocking buffer solution and incubated for 30 min.…”