Abstract

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.

  Funding Agency

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

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Elbahnasawy, Mostafa A; Donius, Luke R; Reinherz, Ellis L et al. (2018) Co-delivery of a CD4 T cell helper epitope via covalent liposome attachment with a surface-arrayed B cell target antigen fosters higher affinity antibody responses. Vaccine 36:6191-6201
Abbott, Robert K; Silva, Murillo; Labuda, Jasmine et al. (2017) The GS Protein-coupled A2a Adenosine Receptor Controls T Cell Help in the Germinal Center. J Biol Chem 292:1211-1217
Silva, Murillo; Nguyen, Thao H; Philbrook, Phaethon et al. (2017) Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes. Cell Rep 21:3672-3680
Song, Likai; Liu, Zhanglong; Kaur, Pavanjeet et al. (2016) Toward increased concentration sensitivity for continuous wave EPR investigations of spin-labeled biological macromolecules at high fields. J Magn Reson 265:188-96
Shrestha, Ruben; Chen, Xuejie; Ramyar, Kasra X et al. (2016) Identification of Surface-Exposed Protein Radicals and A Substrate Oxidation Site in A-Class Dye-Decolorizing Peroxidase from Thermomonospora curvata. ACS Catal 6:8036-8047
Abbott, Robert K; Thayer, Molly; Labuda, Jasmine et al. (2016) Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination. J Immunol 197:4014-4020
Donius, Luke R; Cheng, Yuxing; Choi, Jaewon et al. (2016) Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity. J Virol 90:8875-90
Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J (2016) Beyond antigens and adjuvants: formulating future vaccines. J Clin Invest 126:799-808
Irvine, Darrell J; Hanson, Melissa C; Rakhra, Kavya et al. (2015) Synthetic Nanoparticles for Vaccines and Immunotherapy. Chem Rev 115:11109-46
Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet et al. (2015) Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants. J Clin Invest 125:2532-46

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