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

Mucosal Immunol. 2016 Mar;9(2):414-27. doi: 10.1038/mi.2015.70. Epub 2015 Aug 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / isolation & purification
  • Antibody Affinity
  • Antibody Specificity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Breast Feeding
  • Colostrum / cytology
  • Colostrum / immunology*
  • Colostrum / virology
  • Cross Reactions
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / virology
  • Disease Resistance / immunology
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Female
  • Gastrointestinal Microbiome / immunology
  • HIV Antibodies / biosynthesis
  • HIV Antibodies / chemistry*
  • HIV Antibodies / isolation & purification
  • HIV Envelope Protein gp120 / antagonists & inhibitors*
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / isolation & purification
  • Infant
  • Infectious Disease Transmission, Vertical / prevention & control
  • Milk, Human / chemistry
  • Milk, Human / immunology
  • Milk, Human / virology
  • Pregnancy
  • Symbiosis / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin G