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The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.

T L Jeffries | C R Sacha | J Pollara | J Himes | F H Jaeger | S M Dennison | E McGuire | E Kunz | J A Eudailey | A M Trama | C LaBranche | G G Fouda | K Wiehe | D C Montefiori | B F Haynes | H-X Liao | G Ferrari | S M Alam | M A Moody | S R Permar
Mucosal immunology | 2016

Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.

Pubmed ID: 26242599

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI106380
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI100645
  • Agency: PHS HHS, United States
    Id: 5P30 A1064518
  • Agency: NIAID NIH HHS, United States
    Id: UM1-AI100645-01

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