The purpose of this project is to assist the NIDR initiative in the characterization of the mucosal immune response to HIV, the causative agent of AIDS. Specifically, the objective of the study will be pursued through the following three goals: (1) characterization of the effects of HIV-1 infection on the mucosal antibody response by assembly of patients, collection of samples and tissues, quantitation of antibody levels in salivary and intestinal fluids, measurement of Th1/Th2 responses in mucosal tissues, determination of the frequency of HIV- infected cells in mucosal sites and measurement of the effect of HIV on mucosal immune parameters; (2) determination as to whether humoral immune responses to HIV in mucosal tissues has neutralizing or enhancing activity against HIV by purifying IgG and IgA fractions from saliva and intestinal fluids and assaying their function, by infecting primary mucosal cell populations, by immortalizing B cells from mucosal sites of HIV-infected patients through ESV transformation and characterizing their antigen specificity, by assessing IgA-mediated intracellular or extracellular neutralization of HIV, by assessing mucosal antibody enhancement of HIV infectivity and by assessing the role of non-immune factors in HIV infectivity; and (3) determination of the parameters of mucosal immune responses which impact on vertical transmission of HIV through defining the role of the secretory immune response in breast milk, characterizing the quantity and specificity of HIV antibodies in breast milk and serum, by determining whether breast milk antibodies neutralize or enhance HIV infectivity by correlating these data with subsequent vertical transmission of HIV, by correlating degree of maternal disease with vertical transmission and by assaying for the presence of non-immune antiviral factors in milk.
| Wahl, S M; Worley, P; Jin, W et al. (1997) Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues. Am J Pathol 150:1275-84 |
| Wahl, S M; McNeely, T B; Janoff, E N et al. (1997) Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I. Oral Dis 3 Suppl 1:S64-9 |
