Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Mucosal immunology, 2016-03, Vol.9 (2), p.414-427

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.