Successful control of the AIDS pandemic will require the development of a mucosal vaccine that reduces the likelihood of sexual transmission of the human immunodeficiency viruses (HIV). Adherence of HIV to epithelial cells overlying lymphoid follicles like those present in the rectum may be important in the initiation of viral transcytosis across the epithelial barrier. Immunoglobulin A (IgA) is the predominant antibody on mucosal surfaces. It is a polymeric, protease resistant molecule that is thought to function by aggregating invading bacteria or viruses and/or by sterically hindering contact between pathogens and epithelial host cell receptors. This proposal will test the hypothesis that monoclonal, dimeric IgA directed against the viral envelope proteins of HIV can prevent, or reduce, viral adhesion to epithelial cells. Monoclonal, dimeric IgA antibodies against recombinant forms of gp120 and gp4l will be generated from Peyer's patch lymphocytes from mucosally immunized mice. An assay to measure adherence of HIV to follicle associated epithelium will be developed and used to evaluate the protective effect of anti-envelope IgA antibodies.
| Mantis, Nicholas J; Palaia, Jana; Hessell, Ann J et al. (2007) Inhibition of HIV-1 infectivity and epithelial cell transfer by human monoclonal IgG and IgA antibodies carrying the b12 V region. J Immunol 179:3144-52 |
| Mantis, N J; Kozlowski, P A; Mielcarz, D W et al. (2001) Immunization of mice with recombinant gp41 in a systemic prime/mucosal boost protocol induces HIV-1-specific serum IgG and secretory IgA antibodies. Vaccine 19:3990-4001 |
| Mantis, N J; Frey, A; Neutra, M R (2000) Accessibility of glycolipid and oligosaccharide epitopes on rabbit villus and follicle-associated epithelium. Am J Physiol Gastrointest Liver Physiol 278:G915-23 |
