Abstract

The principal goal of this project is to establish a correlate of broad protective immunity in a HIV-1/HIV-2 cross-protection model in rhesus macaques. This goal stems from our earlier work showing that macaques can be protected against infection with HIV-2 by immunization with HIV-1 antigens using HIV-1 recombinant pox-viruses for priming and HIV-1 soluble subunit proteins for boosting. Given that neither CTLs nor neutralizing antibodies correlated with protection in our model, other effector mechanisms appear to be responsible for protective immunity. In support of this idea, one recent study in a SIV model reported that protection correlated with enhanced release of anti-viral chemokines. Thus, the principal hypothesis of this project is that virus suppressive factors (VSF), comprised of virus inhibitory beta-chemokines (RANTES, MIP-1alpha, MIP-1beta) will be correlates of protective immunity in this model. This hypothesis will be tested in the first two specific aims. The secondary hypothesis of this project is to re-examine other correlates of protein in this model including serum antibody responses and, cell specimens permitting, CTLs. This goal is described in the third specific aim.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI043046-01
Application #
6100235
Study Section
Project Start
1998-05-15
Project End
2000-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Type
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2006) Cholera toxin indirectly activates human monocyte-derived dendritic cells in vitro through the production of soluble factors, including prostaglandin E(2) and nitric oxide. Clin Vaccine Immunol 13:106-15
Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2005) Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo. Infect Immun 73:413-21
Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2004) Calcium signaling through phospholipase C activates dendritic cells to mature and is necessary for the activation and maturation of dendritic cells induced by diverse agonists. Clin Diagn Lab Immunol 11:77-82
Abdelwahab, Sayed F; Cocchi, Fiorenza; Bagley, Kenneth C et al. (2003) HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses. Proc Natl Acad Sci U S A 100:15006-10
Bagley, K C; Shata, M T; Onyabe, D Y et al. (2003) Immunogenicity of DNA vaccines that direct the coincident expression of the 120 kDa glycoprotein of human immunodeficiency virus and the catalytic domain of cholera toxin. Vaccine 21:3335-41
Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2003) An enzymatically active a domain is required for cholera-like enterotoxins to induce a long-lived blockade on the induction of oral tolerance: new method for screening mucosal adjuvants. Infect Immun 71:6850-6
Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2002) Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway. J Leukoc Biol 72:962-9
Bagley, Kenneth C; Abdelwahab, Sayed F; Tuskan, Robert G et al. (2002) Cholera toxin and heat-labile enterotoxin activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cyclic AMP-dependent pathway. Infect Immun 70:5533-9
Devico, Anthony L; Fouts, Timothy R; Shata, Mohamed T et al. (2002) Development of an oral prime-boost strategy to elicit broadly neutralizing antibodies against HIV-1. Vaccine 20:1968-74
Kamin-Lewis, R; Abdelwahab, S F; Trang, C et al. (2001) Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta. Proc Natl Acad Sci U S A 98:9283-8