Abstract

This proposal will explore cellular and molecular mechanisms to induce mucosal and systemic immune responses specific for SIV and HIV through the nasal-associated lymphoreticular tissue (NALT). They will employ non-toxic cholera-toxin mutants as adjuvants in combination with SIV gp130 or HIV gp160 delivered intranasally as a means to understand the induction pathways in both mice and humans. In a separate proposal, they aim to conduct similar studies SIV/macaque model.
In Aim 1, the applicant will characterize murine NALT and associated mucosal tissues after nasal immunization with SIV gp130 (or HIV gp160) with mCT and develop an in vitro human NALT system to assess mCT-induced antigen uptake.
In Aim 2, signal transduction pathways of NALT antigen-specific CD4+ T cells will be analyzed following nasal immunization.
In Aim 3, they will develop and characterize chimeric mCTs which can mimic induction of antigen-specific Th1 or Th2 type responses following nasal immunization.
In Aim 4, they will assess the effects of mCTs on antigen-presenting cells from human tonsils and adenoids for potentiation of Th1-or Th2-type responses.
In Aim 5, they will determine the safety and immunogenicity of a combined gp160 and mCT nasal vaccine in humans in a phase I vaccine trial.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043197-03
Application #
6163946
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Bradac, James A
Project Start
1998-03-15
Project End
2003-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
3
Fiscal Year
2000
Total Cost
$316,622
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

Boyaka, Prosper N (2017) Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems. J Immunol 199:9-16
Martin, Tara L; Jee, Junbae; Kim, Eunsoo et al. (2017) Sublingual targeting of STING with 3'3'-cGAMP promotes systemic and mucosal immunity against anthrax toxins. Vaccine 35:2511-2519
Terrazas, Cesar; Varikuti, Sanjay; Kimble, Jennifer et al. (2016) IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani. FASEB J 30:1135-43
Nair, Manoj S; Lee, Marianne M; Bonnegarde-Bernard, Astrid et al. (2015) Cry protein crystals: a novel platform for protein delivery. PLoS One 10:e0127669
Jee, J; Bonnegarde-Bernard, A; Duverger, A et al. (2015) Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization. Mucosal Immunol 8:735-45
Bonnegarde-Bernard, Astrid; Jee, Junbae; Fial, Michael J et al. (2014) Routes of allergic sensitization and myeloid cell IKK? differentially regulate antibody responses and allergic airway inflammation in male and female mice. PLoS One 9:e92307
Bonnegarde-Bernard, A; Jee, J; Fial, M J et al. (2014) IKK? in intestinal epithelial cells regulates allergen-specific IgA and allergic inflammation at distant mucosal sites. Mucosal Immunol 7:257-67
Cormet-Boyaka, Estelle; Jolivette, Kalyn; Bonnegarde-Bernard, Astrid et al. (2012) An NF-?B-independent and Erk1/2-dependent mechanism controls CXCL8/IL-8 responses of airway epithelial cells to cadmium. Toxicol Sci 125:418-29
Duverger, Alexandra; Carré, Jeanne-Marie; Jee, Junbae et al. (2010) Contributions of edema factor and protective antigen to the induction of protective immunity by Bacillus anthracis edema toxin as an intranasal adjuvant. J Immunol 185:5943-52
Fukuiwa, Tatsuya; Sekine, Shinichi; Kobayashi, Ryoki et al. (2008) A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity. Vaccine 26:4849-59

Showing the most recent 10 out of 63 publications