The first 2 principal component analyses were grouped by transmission intensity (Accra-green, Cape Coast-purple) (D)

The first 2 principal component analyses were grouped by transmission intensity (Accra-green, Cape Coast-purple) (D). Keywords:Atypical Oxypurinol memory B cells, Malaria, Antibody breadth, Malaria antibody avidity Subject terms:Diseases, Infectious diseases, Malaria, Infectious diseases, Malaria == Introduction == Humoral responses that lead to the production of antibodies are critical in protective immunity against the erythrocytic stage ofPlasmodium falciparuminfections13. It has been demonstrated in passive transfer studies where the administration of antibodies from semi-immune adults to symptomatic children resulted in the resolution of febrile illness and subsequent decrease in parasite density4. Several immuno-epidemiological studies have therefore sought to delineate the characteristics of humoral responses in naturally acquired immunity to malaria. Identifying targets of the protective antibodies and understanding the mechanism of antibody function is further critical for the development of malaria vaccines, that induce better protection than the current RTS, S vaccine57. Merozoite antigens are key targets of naturally acquired protective immunity making them promising candidates for vaccine development. Moreover, increasing antibody breadth (the number of antigens to which an individual has higher antibody titres) is linked to protection against malaria7,8. Also, studies have shown that the breadth of Oxypurinol antibody reactivity correlates with transmission intensity implying that repeated exposure increases ones breadth of antibody reactivity7,9. Antibody avidity, a measure of the cumulative binding strength between the antibody and antigen is derived from the affinities of numerous individual non-covalent interactions10. Also, antibody avidity reflects the degree of affinity maturation of antibodies in the Oxypurinol germinal centers and impacts malarial immunity11. Generally with the classical understanding of B cell development, recurrent exposure to an antigen should lead to germinal center reactions driving several rounds of affinity maturation and thereby increasing antibody avidity12. However, evidence suggests that chronic exposure toP. falciparuminfections which interferes with B cell function may disrupt germinal center reactions and compromise affinity maturation1315. Research has shown that repeated exposure toP. falciparuminfection is linked to alterations in B cell sub-set homeostasis which includes the proliferation of atypical MBCs15,16. Atypical memory B cells are a subclass of B cells that lack the surface markers CD21 and CD27. Alterations in the expression of CD11c, CXCR3, CXCR5, inhibitory receptors, and transcription factors such as Tbet are another characteristic of atypical MBC14,17,18. Atypical B cells are generally thought to be dysfunctional with a diminished ability to secrete antibodies in vitro upon stimulation19. It is however not known how alterations in B cell subsets influence antibody breadth and avidity of malaria antibodies. Drawing on our current knowledge of humoral immunity in malaria, we propose that affinity maturation may be impeded in areas of high transmission. However, this limitation may be offset by an increase in antibody breadth. In the present study, we examined how malaria transmission intensity alters peripheral B cell subsets and the relationship with breadth of antibody reactivity, avidities of merozoite-antigen, and antibody function in partially immune adults. == Results == == Demographic and parasitological characteristics of study participants. == The study was a crossectional study conducted in two communities in Ghana; Accra and Cape Coast. Accra is a region of low malaria transmission intensity, with an entomological inoculation rate (EIR) less than 50 infective bites per person per year20. Although the exact EIR for Cape Coast is not known, the Ghana Malaria Indicator Survey conducted in 2019 revealed an 18% malaria prevalence in children living in Cape Coast, compared to a mere 2% prevalence in Accra21. Volunteers were enrolled in the study during two seasons; OctoberNovember, 2020 (minor rainy season) and MayJuly 2021(major rainy season). A total of 200 healthy asymptomatic adults were recruited for the study. The median age of the study subjects was 29 years (Table1). The malaria prevalence among the study population tested by RDT SOD2 was 4% of which all 8 individuals were from Cape Coast. Estimation of parasitaemia using the more sensitive.