HIV Malaria Co-Infection Is Associated with Atypical Memory B Cell Expansion and a Reduced Antibody Response to a Broad Array of <i>Plasmodium falciparum</i> Antigens in Rwandan Adults

<div><p>HIV infected individuals in malaria endemic areas experience more frequent and severe malaria episodes compared to non HIV infected. This clinical observation has been linked to a deficiency in antibody responses to <i>Plasmodium falciparum</i> antigens; however, prior studies have only focused on the antibody response to <0.5% of <i>P</i>. <i>falciparum</i> proteins. To obtain a broader and less-biased view of the effect of HIV on antibody responses to malaria we compared antibody profiles of HIV positive (HIV+) and negative (HIV-) Rwandan adults with symptomatic malaria using a microarray containing 824 <i>P</i>. <i>falciparum</i> proteins. We also investigated the cellular basis of the antibody response in the two groups by analyzing B and T cell subsets by flow cytometry. Although HIV malaria co-infected individuals generated antibodies to a large number of <i>P</i>. <i>falciparum</i> antigens, including potential vaccine candidates, the breadth and magnitude of their response was reduced compared to HIV- individuals. HIV malaria co-infection was also associated with a higher percentage of atypical memory B cells (MBC) (CD19+CD10-CD21-CD27-) compared to malaria infection alone. Among HIV+ individuals the CD4⁺ T cell count and HIV viral load only partially explained variability in the breadth of <i>P</i>. <i>falciparum</i>-specific antibody responses. Taken together, these data indicate that HIV malaria co-infection is associated with an expansion of atypical MBCs and a diminished antibody response to a diverse array of <i>P</i>. <i>falciparum</i> antigens, thus offering mechanistic insight into the higher risk of malaria in HIV+ individuals.</p>