It is now clear that the mucosa of the rectum, gut and vagina of AIDS patients contain HIV infected cells, and that colorectal cell lines can be infected in vitro, indicating that the sexual transmission of HIV is not dependent on the introduction of virus into the blood stream. Particularly if infection through the mucosa is the primary route of HIV infection, it will be necessary to develop immunization strategies which induce immunity at mucosal sites. Systemic immunization is rarely effective in this respect, and mucosal immunity is most often achieved through direct immunization of mucosally-associated lymphoid tissues. Previous studies by this group have shown that female macaques which are systematially primed and mucosally boosted with whole inactivated SIV vaccine in biodegradable microspheres exhibit specific antibodies in their cervico-vaginal secretions and resist vaginal challenge. In this component of the NCVDG SIV virus-like particles (VLPs), rgp130 and DNA expression vectors will be microencapsulated. These vaccines, plus recombinant SIV-poliovirus mini-replicons, will be immunologically evaluated in mice for their effectiveness as systemic and mucosal immunogens in preparation for their testing in the macaque mucosal challenge model. In parallel, microencapsulated HIV VLPs, rgp120, DNA expression vectors and HIV-poliovirus mini-replicons will be evaluated so that those approaches judged most promising on the basis of macaque testing are immediately available for advancement into the chimpanzee model of heterosexual transmission. Immune sera and mucosal secretions from the mice and macaques will be evaluated for their levels and isotype distribution of anti-SIV/HIV and virus neutralizing antibodies. ELISPOT assays will be used to quantitate the number and isotype distribution of specific antibody secreting cells in the spleens and gut lamina propria of mice and the blood mononuclear cells of macaques. In addition, CMI responses by the murine spleen and gut intraepithelial lymphocytes and macaque blood mononuclear cells will be evaluated. The specific objective of the component is to immunologically evaluate immunization approaches so that the most promising can be selectively advanced through macaque and chimpanzee testing.

Project Start
1998-05-15
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Mestecky, Jiri; Wright, Peter F; Lopalco, Lucia et al. (2011) Scarcity or absence of humoral immune responses in the plasma and cervicovaginal lavage fluids of heavily HIV-1-exposed but persistently seronegative women. AIDS Res Hum Retroviruses 27:469-86
Wahl, Sharon M; Redford, Maryann; Christensen, Shawna et al. (2011) Systemic and mucosal differences in HIV burden, immune, and therapeutic responses. J Acquir Immune Defic Syndr 56:401-11
Raska, Milan; Takahashi, Kazuo; Czernekova, Lydie et al. (2010) Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition. J Biol Chem 285:20860-9
Quan, Fu-Shi; Sailaja, Gangadhara; Skountzou, Ioanna et al. (2007) Immunogenicity of virus-like particles containing modified human immunodeficiency virus envelope proteins. Vaccine 25:3841-50
Reeves, R Keith; Fultz, Patricia N (2007) Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells. Virology 365:356-68
Wang, Bao-Zhong; Liu, Weimin; Kang, Sang-Moo et al. (2007) Incorporation of high levels of chimeric human immunodeficiency virus envelope glycoproteins into virus-like particles. J Virol 81:10869-78
Liao, Hua-Xin; Sutherland, Laura L; Xia, Shi-Mao et al. (2006) A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses. Virology 353:268-82
Gao, Feng; Korber, Bette T; Weaver, Eric et al. (2004) Centralized immunogens as a vaccine strategy to overcome HIV-1 diversity. Expert Rev Vaccines 3:S161-8
Fultz, Patricia N; Stallworth, Jackie; Porter, Donna et al. (2003) Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease. Virology 315:425-37