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

Publication ,  Journal Article
Jeffries, TL; Sacha, CR; Pollara, J; Himes, J; Jaeger, FH; Dennison, SM; McGuire, E; Kunz, E; Eudailey, JA; Trama, AM; LaBranche, C; Fouda, GG ...
Published in: Mucosal Immunol
March 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.

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Published In

Mucosal Immunol

DOI

EISSN

1935-3456

Publication Date

March 2016

Volume

9

Issue

2

Start / End Page

414 / 427

Location

United States

Related Subject Headings

  • Symbiosis
  • Pregnancy
  • Milk, Human
  • Infectious Disease Transmission, Vertical
  • Infant
  • Immunology
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Infections
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jeffries, T. L., Sacha, C. R., Pollara, J., Himes, J., Jaeger, F. H., Dennison, S. M., … Permar, S. R. (2016). The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol, 9(2), 414–427. https://doi.org/10.1038/mi.2015.70
Jeffries, T. L., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, et al. “The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.Mucosal Immunol 9, no. 2 (March 2016): 414–27. https://doi.org/10.1038/mi.2015.70.
Jeffries TL, Sacha CR, Pollara J, Himes J, Jaeger FH, Dennison SM, et al. 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.
Jeffries, T. L., et al. “The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.Mucosal Immunol, vol. 9, no. 2, Mar. 2016, pp. 414–27. Pubmed, doi:10.1038/mi.2015.70.
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. The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol. 2016 Mar;9(2):414–427.

Published In

Mucosal Immunol

DOI

EISSN

1935-3456

Publication Date

March 2016

Volume

9

Issue

2

Start / End Page

414 / 427

Location

United States

Related Subject Headings

  • Symbiosis
  • Pregnancy
  • Milk, Human
  • Infectious Disease Transmission, Vertical
  • Infant
  • Immunology
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Infections