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ARRA Investments in Basic HIV Vaccine Research

Public Health Burden
Although progress has been made in the global fight against HIV/AIDS, the epidemic continues to devastate the United States and the international community with 56,300 new HIV infections each year in the U.S. and an estimated 33 million people living with HIV worldwide. Of the ~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 and 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. The NIH is increasing the emphasis on innovative discovery research for HIV vaccines. A variety of ARRA-funded projects are exploring the molecular mechanisms of HIV infection and the immune response to HIV in order to inform the design of new vaccines. A few examples are:
  • Determining whether the failure to make a protective antibody response to HIV is a consequence of B cells being deleted because they cross-react with host molecules that look like parts of HIV.1
  • Analyzing the molecular mechanisms underlying how the virus exits one cell in order to be able to infect another.2
  • Examining the role of a receptor involved in cell death in order to increase the ability of HIV-specific T cells to control the disease.3
  • Examining the capacity of CD4 T cells to produce proteins that protect cells from HIV while they perform their immune functions.4
  • Determining whether altering the HIV envelope protein can induce a stronger immune response.5
  • Understanding the events at the mucosa: investigating the basic mechanisms of immune response in mucosal tissue following vaccination or infection,6 and identifying synthetic compounds that can increase the mucosal immune response to HIV.7
  • Identifying measurable signs of HIV vaccine-mediated protection or failure, in order to identify critical elements of the immune response and facilitate clinical studies.8
  • Investigating how parasitic worms that suppress the immune system may affect the testing of HIV-1 vaccine candidates in developing countries.9
  • Searching for and characterizing neutralizing antibodies that can broadly recognize HIV and block infection by studying people who naturally control HIV10 , examining how viruses combine and what antibodies are produced in patients infected with multiple HIV-1 strains11, and investigating whether stable forms of an HIV peptide can induce broadly neutralizing antibodies against HIV-112.
  • Following individuals at high risk of HIV infection to elucidate the mechanisms by which the virus blocks the establishment of effective immune responses during early infection13.
Vaccine Development
In addition, NIAID continues to support the development and preclinical testing of novel vaccine candidates. ARRA funds were used to support many of these projects, such as:
  • Examining the viability of new vaccine candidates, such as ones based on modified coxsackieviruses, 14, on a genetically engineered version of the HIV virus that can replicate and infect cells without causing disease 15; and studying a two-injection adenovirus prime-boost regimen that may overcome current challenges with HIV-1 vaccine candidates.16
  • Evaluating novel vaccine candidates in an animal model to examine their protective power in response to exposure to the animal virus equivalent of HIV.17,18
  • Exploring an HIV vaccination approach that delivers viral antigens directly to mucosal tissue, the site of primary replication of the virus.19
  • Developing safer oral adenoviral vaccines against HIV for simpler vaccination in developed and less developed countries.20

  1. 1R01AI081579-01 -- B cell Tolerance and Humoral Immunity to HIV-1 -- Kelsoe, Garnett H (NC)
  2. 1F31AI083010-01 -- A Molecular Analysis of Exosome Biogenesis and Retrovirus Budding -- Carcamo, Jose R (MD)
  3. 1R21AI076161-01A2W1 -- Enhancement of HIV-specific CD4+ T Cell Function by Blockade of the PD-1 Pathway -- Palmer, Brent E (CO)
  4. 1R01AI084807-01 -- CC Chemokine Secretion to Protect Antigen-Specific CD4 T Cells from HIV -- Hioe, Catarina E (NY)
  5. 1R01AI080367-01A2 -- HIV ENV Epitope Engineering -- Landry, Samuel (LA)
  6. 1F32AI082881-01, -- Enterococcus faecalis Gene Expression in Host Environments -- Frank, Kristi (MN); AI 084622-01 -- Effect of Antigen Exposure on T Cell Quantity and Quality in Mucosal Tissues --Fraser, Kathryn (MN)
  7. 1R21AI078898-01A2 -- Alpha-galactosycleramide as a Mucosal Adjuvant for HIV Antigens -- Sastry, Jagannadha (TX)
  8. 1P01AI082278-01 -- Mechanisms of Protection from and Enhanced Susceptibility to HIV Infection -- Miller, Christopher J (CA)
  9. 1R01AI071883-01A2 -- The Effect of Helminth Infection on HIV-1 Vaccines -- Harn, Donald A (GA)
  10. 1R01AI084830-01 -- Broad Neutralizing Monoclonal Antibodies From HIV Controllers -- Lewis, George K (MD)
  11. 1R56AI083142-01A1 -- Viral Evolution and Humoral Immune Response due to Dual HIV-1 Infection -- Nyambi, Phillipe N (NY)
  12. 1R21AI078466-02W1 -- Presentation of Structural Determinants of the 2F5 Neutralization Epitope -- Lu, Min (NY)
  13. 1P01AI057127-05S1 -- Immunopathogenesis of Acute and Early HIV Infection -- Valentine, Fred (NY)
  14. 1R01AI066938-04S1 -- HIV Vaccine Development Using Recombinant Coxsackieviruses -- Ramsingh, Arlene (NY)
  15. 1R21AI084596-01 -- A Propagating Chimeric Particle as a Safe Alternative Attenuated Virus -- Young, Kelly (NC)
  16. 1U19AI078526-02W1 -- Novel Heterologous Adenovirus Prime-Boost HIV-1 Vaccine -- Barouch, Dan H (MA)
  17. 1R03AI078777-01 -- Evaluation of Ad5-gag &innovative Ad5-E2b-gag vaccines in Ad-immune Cynomolgus M -- Wu, Younong (WA)
  18. 1R33AI073234-03S1 -- Induction of Mucosal SIV Immunity in Non Human Primates by Secreted Hsp-Gp96 -- Podack, Eckhard R (FL)
  19. 1R56AI084171-01 -- Epithelial Cells as Mucosal Adjuvant for Life Long Immunity -- Gauduin, Marieclaire Elisabeth (TX)
  20. 1R56AI067095-06A1 -- Mucosal Helper-dependent Adenovirus Vaccines Against HIV -- Barry, Michael A (MN)

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