A Molecular Analysis of Memory B Cell and Antibody Responses Against Plasmodium falciparum Merozoite Surface Protein 1 in Children and Adults From Uganda.

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire.

Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective?

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.