Acquired Mucosal Antibodies to HIV

Rhoda Ashley, PhD

This research study is concerned with characterization of the antibody component of HIV-specific mucosal immunity and its function in infected adults and pregnant women. The common mucosal immune response results in antibody production and cellular immune functions at entry sites for pathogens. In other virus infections, mucosal antibodies elicited by natural infection or induced by immunization can be seen in rectal, genital and oral secretions and have been shown to be protective against challenge antibodies. Antibodies to HIV have been demonstrated in saliva, semen, colostrum and milk, and in rectal or genital secretions of infected patients. The overall goal of this study is to provide a systematic description of the local mucosal antibodies elicited by HIV infection. This study has a companion project CMIG for AIDS Vaccines, PI- Juliana McElrath) which is studying the HIV-specific CTL and helper T-cells in the mucosal epithelium.

The specific aims of this study are to:

1. Quantitate isotype-specific mucosal HIV antibody responses to denatured and native HIV proteins.
2. Compare local antibody titers with HIV titers in local and peripheral blood compartments and with HIV-specific cellular immune functions (from the companion project) to determine the extent and mechanism of immune viral clearance.
3. Determine the strain-related variability of local functional antibodies. Local IgG and IgA-mediated neutralizing antibodies, from patients with recent or long-standing HIV infections, are being anlayzed against both autologous and prototype HIV strains.
4. Correlate the presence of antibodies in cervix or milk with intrapartum or neonatal transmission, respectively. HIV protein-specific, isotype-specific and neutralizing antibodies to HIV are measured in pre- and postnatal cervical secretions and in milk samples.

This research project has been successful in developing reproducible sampling methods and extremely sensitive protein-specific IgG, IgA and IgM-detection techniques. An enhanced chemiluminescent Western immunoblot (ECL-WB) and enzyme immunoassay (ECL-EIA) have been used to quantify and characterize antibodies in cervical, rectal and salivary secretions.

Report courtesy of Anna Marie Beckmann

Recent Publications

Edghill-Smith YY, Dalessio J, Schacker T, Corey L, Ashley RL. Limited rectal antibody responses to primary infection with human immunodeficiency virus. (to submit to AIDS Res. and Hum. Retroviruses).