Our understanding of the biology of the innate immune systems is rapidly expanding. We are gaining an increasing understanding of the receptors expressed by NK cells that specifically mediate the inhibition and activation of these cells, as well as the ligands for these receptors. It is becoming clear that innate immune signals can dramatically modulate adaptive immune response. Emerging data are implicating NK cells and Other innate immune responses in the early control of HIV-1 replication during primary infection. The recent demonstration that it is possible to generate memory responses in the innate immune system raises the possibility that it may be feasible to use vaccines to enhance anti-viral innate immunity to help terminate or control very early HIV-1 infection. We will explore this possibility in the following aims:
Aim 1. Recombinant canary-pox elicited innate responses and their contribution to shaping adaptive immune responses in rhesus monkeys Aim 2. Vaccination with KIR ligands for induction of immunologic memory for innate NK cell responses in rhesus monkeys and humans Aim 3. CD8+ T cell-produced factors and control of viremia The information gained in these studies about the anti-SIV and anti-HIV protective capacity of innate immune responses will lead directly to advances in vaccine design.

Public Health Relevance

Early in acute HIV-1 infection innate immune responses are activated and evidence suggests that they are important in the potential control of the virus. Recent studies suggest a form of virus-induced innate memory. Therefore, it is important to determine if HlV-1 vaccines can induce innate memory to augment protective immune responses to HIV-1 infection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZAI1-JBS-A)
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Duke University
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Chen, Shuobing; Wu, Jiayi; Lu, Ying et al. (2016) Structural basis for dynamic regulation of the human 26S proteasome. Proc Natl Acad Sci U S A 113:12991-12996
Tian, Ming; Cheng, Cheng; Chen, Xuejun et al. (2016) Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell 166:1471-1484.e18
Love, Tanzy M T; Park, Sung Yong; Giorgi, Elena E et al. (2016) SPMM: estimating infection duration of multivariant HIV-1 infections. Bioinformatics 32:1308-15
Barton, John P; Goonetilleke, Nilu; Butler, Thomas C et al. (2016) Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable. Nat Commun 7:11660
Astronomo, Rena D; Santra, Sampa; Ballweber-Fleming, Lamar et al. (2016) Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine 14:97-111
Herschhorn, Alon; Ma, Xiaochu; Gu, Christopher et al. (2016) Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins. MBio 7:
Theiler, James; Yoon, Hyejin; Yusim, Karina et al. (2016) Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci Rep 6:33987
Ding, Shilei; Tolbert, William D; Prévost, Jérémie et al. (2016) A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. J Virol 90:8395-409
Jeffries Jr, T L; Sacha, C R; Pollara, J et al. (2016) The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol 9:414-27
Abdul-Jawad, Sultan; Ondondo, Beatrice; van Hateren, Andy et al. (2016) Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition. Mol Ther 24:375-84

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