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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jeffries, TL; Sacha, CR; Pollara, J; Himes, J; Jaeger, FH; Dennison, SM; McGuire, E; Kunz, E; Eudailey, JA; Trama, AM; LaBranche, C; Fouda, GG; Wiehe, K; Montefiori, DC; Haynes, BF; Liao, H-X; Ferrari, G; Alam, SM; Moody, MA; Permar, SR

Published Date

  • March 2016

Published In

Volume / Issue

  • 9 / 2

Start / End Page

  • 414 - 427

PubMed ID

  • 26242599

Pubmed Central ID

  • 26242599

Electronic International Standard Serial Number (EISSN)

  • 1935-3456

International Standard Serial Number (ISSN)

  • 1933-0219

Digital Object Identifier (DOI)

  • 10.1038/mi.2015.70

Language

  • eng