Naturally acquired antibodies to gametocyte antigens are associated with reduced transmission of Plasmodium vivax gametocytes to Anopheles arabiensis mosquitoes

Abstract

Naturally acquired antibodies may reduce the transmission of Plasmodium gametocytes to mosquitoes. Here, we investigated associations between antibody prevalence and P. vivax infectivity to mosquitoes. A total of 368 microscopy confirmed P. vivax symptomatic patients were passively recruited from health centers in Ethiopia and supplemented with 56 observations from asymptomatic P. vivax parasite carriers. Direct membrane feeding assays (DMFA) were performed to assess mosquito infectivity; for selected feeds these experiments were also performed after replacing autologous plasma with malaria naïve control serum (n=61). The prevalence of antibodies against 6 sexual stage antigens (Pvs47, Pvs48/45, Pvs230, PvsHAP2, Pvs25 and PvCelTOS) and an array of asexual antigens was determined by ELISA and multiplexed bead-based assays. Gametocyte (ρ< 0.42; p = 0.0001) and parasite (ρ = 0.21; p = 0.0001) densities were positively associated with mosquito infection rates. Antibodies against Pvs47, Pvs230 and Pvs25 were associated with 23 and 34% reductions in mosquito infection rates (p<0.0001), respectively. Individuals who showed evidence of transmission blockade in serum-replacement DMFAs (n=8) were significantly more likely to have PvsHAP2 or Pvs47 antibodies. Further studies may demonstrate causality for the observed associations, improve our understanding of the natural transmission of P. vivax and support vaccine development.

Naturally Acquired Transmission-Blocking Immunity Against Different Strains of Plasmodium vivax in a Malaria-Endemic Area in Thailand

“…It seems that neither the breadth nor the intensity of antibody responses against individual Pvs25, Pvs28, and Pvs230 antigens could explain the TBI. While the antibody titers against 3 antigens strongly correlated—as noted in a recent study by Tebeje et al [ 16 ], where strong correlations were seen among different antigens (including P vivax blood- and sexual-stage antigens)—some high-blocking, strain-transcending, and IgG-dependent plasma samples (eg, VYBN-020 and VTTY-119) had relatively lower MFI values vs all 3 antigens. It is challenging to determine the mechanisms of naturally acquired TBI.…”

“…The results suggest that there could be unidentified transmission-blocking vaccine (TBV) candidates. In the case of P vivax , a recent study revealed that antibodies against Pvs47, Pvs230, Pvs25, and PvHAP2 were associated with naturally acquired TBI [ 16 ]. In addition to these antigens, Pvs28 has been considered a promising TBV candidate [ 17 ], although the naturally acquired TBI against Pvs28 has never been investigated.…”

Evaluation of transmission-blocking potential of PvPSOP25 using transgenic murine malaria parasite and clinical isolates

“…Until now, the effective method for identifying potential candidates for P . vivax vaccines has been through studies of naturally acquired immunity in endemic populations [ 12 ] or in silico analysis and computational screening [ 13 ]. Besides, chimeric P .…”