A high mucosal blocking score is associated with HIV protection

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Early HIV infection involves envelope binding to mucosal receptors (α4β7, DC-SIGN, langerin).
• Env-specific B-cell responses are documented in highly exposed seronegative individuals (HESN).

Purpose of the Study:

• To investigate gp120-specific antibody capacity to block HIV interaction with mucosal receptors in HESN.
• To develop and validate a mucosal blocking score (MBS) for assessing antibody function in HESN.

Main Methods:

• Developed novel cell-based assays to measure antibody-mediated inhibition of gp120 binding to α4β7, DC-SIGN, and langerin.
• Defined a mucosal blocking score (MBS) based on antibody interference with these binding interactions.
• Evaluated MBS in 86 HESN individuals, comparing them to HIV+ patients and HIV- unexposed controls.

Main Results:

• Antibodies reducing gp120 binding to both α4β7 and DC-SIGN were detected in HESN serum and mucosal secretions.
• Antibodies from HIV+ patients, conversely, enhanced gp120 binding to DC-SIGN.
• No correlation was found between MBS and the neutralization of primary HIV isolates infecting α4β7 CD4+ T cells.

Conclusions:

• The mucosal blocking score (MBS) is significantly associated with protection in HESN.
• MBS may indicate reduced HIV dissemination to mucosal-associated lymphoid tissues in protected individuals.