Malaria Immunology and Pathogenesis in Pregnant Women and Young Children

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In FY 2019, we conducted human and animal studies to investigate malaria immunology and pathogenesis in pregnant women and children. Highlighted in this years summary are results from our publications. 1. Attaher O, et al. Effect of seasonal malaria chemoprevention on immune markers of exhaustion and regulation. 2019. Journal of Infectious Diseases. In press. Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. In this study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry. Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC, and SMC+ children showed greater increases in CD4+FOXP3+ T regulatory cells compared to SMC- children. Thus, reduction of malaria infections due to seasonal malaria chemoprevention may prevent immune dysfunction. 2. Park S, et al. Impact of maternally derived antibodies to Plasmodium falciparum Schizont Egress Antigen-1 on the endogenous production of anti-PfSEA-1 in offspring. 2019. Vaccine. 14;37(35):5044-5050. Using samples and data from our birth cohort studies, our collaborators at brown and we evaluated whether maternally-derived antibodies to a malarial vaccine candidate, Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), in cord blood interfered with the development of infant anti-PfSEA-1 antibodies in response to natural exposure. We found that maternally-derived anti-PfSEA-1A antibodies in cord blood did not abrogate the parasitemia driven development of infant anti-PfSEA-1A: parasitemia were significantly correlated with anti-PfSEA-1A antibody levels at 6months of age in the infants born with low maternally-derived anti-PfSEA-1A antibody levels in cord blood and borderline significantly correlated in those infants born with middle and high levels. Maternal vaccination with PfSEA-1A is unlikely to interfere with the development of naturally acquired anti-PfSEA-1A immune responses following exposure during infancy. 3. Doritchamou J, et al. Functional antibodies against placental malaria parasites are variant-dependent and differ by geographic region. 2019. Infection and Immunity. Jun 20;87(7). Here, we assayed plasma collected at delivery from Malian and Tanzanian women of different parities for total antibody levels against recombinant VAR2CSA antigens (FCR3 allele), and for surface reactivity and binding inhibition and opsonizing functional activities against IE using two CSA-binding laboratory isolates (FCR3 and NF54). Plasma from Malian gravid women reacted more strongly with FCR3 whereas Tanzanian plasma preferentially reacted with NF54. Further, acquisition of functional antibodies (binding-inhibitory or opsonizing) was variant dependent. Thus, IE surface-expressed epitopes involved in each functional activity may differ among P. falciparum strains. Consequently, geographic bias in circulating strains may impact antibody functions, and this should be considered for the development of PM vaccines aiming to achieve broad protection against various parasite strains.