Abstract

The overall objective of this proposal is to investigate mucosal strategies resulting in the induction of mucosal and systemic, humoral and cellular immune responses against SIV/HIV. The entire application considers recent advances in novel antigen delivery systems and immunizations routes suitable for mucosal immunization, to effectively stimulate both humoral and cellular arms of the immune response. The proposed studies will be performed by investigators with well-established collaborative tissues and expertise in HIV/SIV virology, pathogenesis, and immunology with emphasis on mucosal immunity. The proposal consists of five inter-related projects: Project 1. Mucosal DNA and Protein Vaccines for AIDS Prevention (Dr. R.W. Compans, P.I., Emory University). Novel DNA vectors and virus-like particles for effective mucosal delivery will be developed to induce mucosal and systemic immune responses; Project 2. Poliovirus Replicons for HIV/SIV Vaccines (Dr. C. Morrow, P.I., UAB). Proposed studies are designed to optimize poliovirus replicons as mucosal vaccine vectors for HIV/SIV antigens; Project 3. Non-human Primate Models for HIV Vaccine Evaluation (Dr. P. Fultz, P.I., UAB). Primate models will be utilized to evaluate the immunogenicity of SIV/HIV antigens provided by investigators involved in Projects 1 & 2 (DNA vectors, virus-like particles, and poliovirus replicons) and given by both mucosal and parenteral routes. Humoral and cellular immune responses in mucosal and systemic immune compartments will be evaluated in collaboration with other participating investigators; Project 4. Novel technologies for Measuring AIDS Virus-Specific CTL in Non-Human Primates (Dr. N. Letvin, P.I.,) Beth Israel Deaconess Medical Center). Primate models will be used to explore virus-specific CTL responses induced by infection and mucosal immunization with antigens generated by investigators in Projects 1 and 2; Project 5. Mucosal Immunization Strategies for Genital Immunity (Dr. J. Mestecky, P.I., UAB)> Immunization strategies that induce mucosal and systemic humoral and cellular immune responses will be investigated in humans with particular emphasis on the immune system of the male genital tract.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI028147-12
Application #
6170172
Study Section
Special Emphasis Panel (ZAI1-VSG-A (J1))
Program Officer
Bradac, James A
Project Start
1989-03-01
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
12
Fiscal Year
2000
Total Cost
$1,603,662
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

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