Abstract

Successful development of a vaccine against HIV will likely require the induction of both antibody and/or cellular immune responses sufficient to prevent infection or disease respectively following infectious challenge. While the induction of antibody responses for a variety of other infectious pathogens is readily achieved by a variety of vaccine formulations, live attenuated, recombinant viral vaccines or plasmid DNA vaccines only induce the induction of long-lived cellular immune responses, particularly CD8+ T cell responses. Moreover, since live attenuated HIV vaccines might be precluded from use due to safety concerns and DNA vaccines at present only induce modest CD8+ T cell responses in humans, there is an urgent need to develop ways to enhance the generation and maintenance of CD8+ T cell responses in humans in following immunization. This study focuses on how to optimize the magnitude and duration of CD8+ T cell responses following vaccination in rodents and primates using a variety of vaccine formulations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005016-06
Application #
7592387
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2007
Total Cost
$621,788
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Quinn, Kylie M; Da Costa, Andreia; Yamamoto, Ayako et al. (2013) Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus gag-specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant adenoviral vector immunization. J Immunol 190:2720-35
Park, Haesun; Adamson, Lauren; Ha, Tae et al. (2013) Polyinosinic-polycytidylic acid is the most effective TLR adjuvant for SIV Gag protein-induced T cell responses in nonhuman primates. J Immunol 190:4103-15
Foulds, Kathryn E; Rotte, Masashi J; Paley, Michael A et al. (2008) IFN-gamma mediates the death of Th1 cells in a paracrine manner. J Immunol 180:842-9
Seder, Robert A; Darrah, Patricia A; Roederer, Mario (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8:247-58
Darrah, Patricia A; Patel, Dipti T; De Luca, Paula M et al. (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13:843-50
Wille-Reece, Ulrike; Flynn, Barbara J; Lore, Karin et al. (2006) Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med 203:1249-58
Wille-Reece, Ulrike; Flynn, Barbara J; Lore, Karin et al. (2005) HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci U S A 102:15190-4
Wille-Reece, Ulrike; Wu, Chang-You; Flynn, Barbara J et al. (2005) Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses. J Immunol 174:7676-83
Barouch, Dan H; Letvin, Norman L; Seder, Robert A (2004) The role of cytokine DNAs as vaccine adjuvants for optimizing cellular immune responses. Immunol Rev 202:266-74
Tritel, Marc; Stoddard, Amy M; Flynn, Barbara J et al. (2003) Prime-boost vaccination with HIV-1 Gag protein and cytosine phosphate guanosine oligodeoxynucleotide, followed by adenovirus, induces sustained and robust humoral and cellular immune responses. J Immunol 171:2538-47