Potential Targets of Naturally Acquired Plasmodium vivax Transmission - Reducing Antibodies

Abstract

BACKGROUND: Malaria transmission-blocking vaccines induce functional immunity, impeding Plasmodium parasite development in mosquitoes and thereby reducing malaria transmission. We aim to identify target antigens of naturally acquired transmission-blocking antibodies against Plasmodium vivax. METHODS: Thirty plasma samples obtained from Thai P. vivax patients were evaluated for the presence of IgM and IgG antibodies against a library of 659 P. vivax recombinant proteins expressed by the wheat germ cell-free protein expression system using AlphaScreen. Spearman's rank tests were used to compare the antibody levels and transmission-reducing activity (TRA) of the plasma samples, measured by direct membrane feeding assay. RESULTS: Most proteins were immunoreactive to IgM (85.4%) and IgG (97.9%). TRA is significantly correlated with the level of IgM and IgG to 89 and 8 antigens (p < 0.05), respectively. Notably, IgM responses against the N-terminal Pvs230 was identified. After false discovery rate adjustment, significant correlations of TRA and IgM responses to 11 antigens remained. Some of those TRA-associated antigens exhibited elevated IgM levels in individuals with significant TRA compared to those with non-significant TRA. CONCLUSION: Our findings demonstrate the association of IgM with naturally acquired transmission-blocking immunity and highlight potential targets of P. vivax transmission-reducing antibodies. Further investigations are needed to validate the targets, elucidate the underlying mechanisms and facilitate the research on transmission-blocking vaccines.