It is believed that innovative adjuvants might be capable of inducing higher titers of broadly neutralizing anti-HIV-1 antibodies and better anti-HIV-1 T-cell responses. We propose to explore a novel opportunity to improve the effectiveness of anti-HIV vaccines by using anti-adenosinergic

Public Health Relevance

importance, translating this novel HIV vaccination strategy into human trials can be accelerated since the co-adjuvants to be tested are drugs that are readily available and safe. Of relevance to the AIDS epidemic, even caffeine, the inexpensive natural A2AR antagonist, substantially enhanced the vaccination-induced anti-HIV IgGI, lgG2a and IgM levels if combined with otherwise weak adjuvants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI091693-04
Application #
8516452
Study Section
Special Emphasis Panel (ZAI1-PTM-A)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$251,912
Indirect Cost
$38,083
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Verkoczy, Laurent; Kelsoe, Garnett; Haynes, Barton F (2014) HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development. PLoS Pathog 10:e1004073
Hanson, Melissa C; Bershteyn, Anna; Crespo, Monica P et al. (2014) Antigen delivery by lipid-enveloped PLGA microparticle vaccines mediated by in situ vesicle shedding. Biomacromolecules 15:2475-81
Sitkovsky, Michail V; Hatfield, Stephen; Abbott, Robert et al. (2014) Hostile, hypoxia-A2-adenosinergic tumor biology as the next barrier to overcome for tumor immunologists. Cancer Immunol Res 2:598-605
Sun, Zhen-Yu J; Cheng, Yuxing; Kim, Mikyung et al. (2014) Disruption of helix-capping residues 671 and 674 reveals a role in HIV-1 entry for a specialized hinge segment of the membrane proximal external region of gp41. J Mol Biol 426:1095-108
Liu, Haipeng; Moynihan, Kelly D; Zheng, Yiran et al. (2014) Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507:519-22
Holl, T Matt; Yang, Guang; Kuraoka, Masayuki et al. (2014) Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol 192:3269-79
Irvine, Darrell J; Swartz, Melody A; Szeto, Gregory L (2013) Engineering synthetic vaccines using cues from natural immunity. Nat Mater 12:978-90
Kim, Mikyung; Song, Likai; Moon, James et al. (2013) Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem 288:31888-901
Cain, Derek W; Sanders, Sergio E; Cunningham, Michael M et al. (2013) Disparate adjuvant properties among three formulations of "alum". Vaccine 31:653-60
Moon, James J; Suh, Heikyung; Li, Adrienne V et al. (2012) Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc Natl Acad Sci U S A 109:1080-5

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