ARRA IMPACT REPORT:
Research Builds Fundamental Knowledge Toward an HIV Vaccine


Public Health Burden
Although progress has been made in the global fight against HIV/AIDS, the epidemic continues to challenge the United States and the international community, with approximately 50,000 new HIV infections each year in the United States and an estimated 34.2 million people living with HIV worldwide.1,2 Of the roughly 1.1 million individuals living with HIV in the United States, 21 percent are unaware of their infection.

Vaccine Discovery
The development of safe and effective HIV vaccines remains one of the highest priorities for HIV scientists and one of the greatest challenges in biomedical research. Designing an HIV vaccine will require significant advances in fundamental research to expand our understanding of the virus and the disease. ARRA funds supported several discovery studies exploring the molecular mechanisms of HIV infection and the immune response to HIV, knowledge that will inform the design of new vaccines.

  • Insights into Early Immune Response to HIV Infection: Led by a group at New York University, scientists at several institutions used ARRA funding to extend their studies of the immune response that occurs shortly after HIV infection. Focusing on dendritic cells (DCs), which play a critical role in the early immune response to infection, they demonstrated that shortly after initial infection with HIV, DCs that survived and remained in the blood were hyper-responsive. These findings implicate DCs as a likely contributor to the chronic immune activation that is a hallmark of HIV infection.3
  • Insight into HIV Viral Transmission – Semen Amyloids: ARRA funds allowed researchers at the University of Rochester to study amyloid fibrils isolated from human semen. These clumps of protein have been shown to increase the infectivity of HIV. Studies conducted by these researchers have contributed to the biochemical understanding of how amyloid fibrils form in semen under physiologic conditions, providing further insight into viral transmission and establishing potential targets for vaccine design.4
  • Improving HIV Vaccine Design and Testing: Researchers at the Dana-Farber Cancer Institute in Boston received ARRA funding to augment their ongoing HIV Vaccine Research and Design (HIVRAD) Program project and hire and train additional lab personnel. In collaboration with colleagues at several other institutions, the resulting research efforts led to the development of a novel method for isolating monoclonal antibodies with predetermined specificity for a particular target.5 A patent application for this novel technology, which will allow for improved vaccine design and testing, was subsequently submitted to the U.S. Patent Office.6
  • ARRA-funded investigators at Tulane University conducted experiments to determine how alterations in the structure of the HIV envelope glycoprotein—a potential vaccine target—affect the immune response to the virus. They characterized T-cell and antibody responses resulting from specific engineered changes in the protein, providing important fundamental knowledge to inform vaccine design.7

Vaccine Development
NIH used ARRA funds to continue support for the development and preclinical testing of novel HIV vaccine candidates. Researchers at the University of Miami tested the immunogenicity of a vaccine candidate for SIV (the animal virus equivalent of HIV) in a non-human primate model. The studies demonstrated the ability of this approach to generate high levels of virus-specific immune cells in the mucosal locations of the body where the virus is most likely to enter the host.8

Contributing NIH Institutes & Centers

  • National Institute of Allergy and Infectious Diseases (NIAID)

  1. http://www.ncbi.nlm.nih.gov/pubmed/21826193
  2. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/201207_FactSheet_Global_en.pdf
  3. 3P01AI057127-05S1, http://www.ncbi.nlm.nih.gov/pubmed/20693428 - VALENTINE, FRED T - NEW YORK UNIVERSITY SCHOOL OF MEDICINE - NEW YORK - NY
  4. 1R01AI084111-01, http://www.ncbi.nlm.nih.gov/pubmed/22354963 - DEWHURST, STEPHEN - UNIVERSITY OF ROCHESTER - ROCHESTER - NY
  5. 3P01AI048240-08S1, http://www.ncbi.nlm.nih.gov/pubmed/22737224 - RUPRECHT, RUTH MARGRIT - DANA-FARBER CANCER INST - BOSTON - MA
  6. Patent Application #PCT/US2010/046353 Mimotopes of HIV and Uses Thereof (filed 8/23/2010)
  7. 1R01AI080367-01A2, http://www.ncbi.nlm.nih.gov/pubmed/20089653 - LANDRY, SAMUEL JOHN - TULANE UNIVERSITY OF LOUISIANA - NEW ORLEANS - LA
  8. 3R33AI073234-03S1, http://www.ncbi.nlm.nih.gov/pubmed/21277409 - PODACK, ECKHARD R - UNIVERSITY OF MIAMI SCHOOL OF MEDICINE - MIAMI - FL