title: HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life.
abstract: Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected.
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya Enduati@kemri-wellcome.org.
authors.forename: Eunice W
authors.initials: EW
authors.lastname: Nduati
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya.
authors.forename: Irene N
authors.initials: IN
authors.lastname: Nkumama
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya.
authors.forename: Faith K
authors.initials: FK
authors.lastname: Gambo
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Muema
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Miguel G
authors.identifier: 0000-0001-9556-3719
authors.initials: MG
authors.lastname: Knight
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya.
authors.forename: Amin S
authors.initials: AS
authors.lastname: Hassan
authors.affiliation: Kilifi County Hospital, Kilifi, Kenya.
authors.forename: Margaret N
authors.initials: MN
authors.lastname: Jahangir
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Etyang
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research Coast, Kilifi, Kenya Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Berkley
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool University, Liverpool, United Kingdom.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D004781:Environmental Exposure; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007231:Infant, Newborn; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D011247:Pregnancy