HIV Malaria Co-Infection Is Associated with Atypical Memory B Cell Expansion and a Reduced Antibody Response to a Broad Array of Plasmodium falciparum Antigens in Rwandan Adults.
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 Plasmodium falciparum antigens; however, prior studies have only focused on the antibody response to <0.5% of P. falciparum 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 P. falciparum 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 P. falciparum 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 P. falciparum-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 P. falciparum antigens, thus offering mechanistic insight into the higher risk of malaria in HIV+ individuals.
Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
Krishanthi S
KS
Subramaniam
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, NIAID/NIH, Bethesda, Maryland, United States of America.
Jeff
J
Skinner
Department of Biomedical Laboratory Sciences, University of Rwanda, College of Medicine and Health Sciences, Kigali, Rwanda.
Emil
E
Ivan
Regional Alliance for Sustainable Development, Kigali, Rwanda.
Eugene
E
Mutimura
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Ryung S
RS
Kim
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Catherine M
CM
Feintuch
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, NIAID/NIH, Bethesda, Maryland, United States of America.
Silvia
S
Portugal
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Kathryn
K
Anastos
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, NIAID/NIH, Bethesda, Maryland, United States of America.
Peter D
PD
Crompton
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Johanna P
JP
Daily
D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D060085:Coinfection / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity*; D055815:Young Adult
D000953:Antigens, Protozoan