Laboratory of Immunoregulation and

Laboratory of Immunoregulation and


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PubMed | Maple Leaf Medical Clinic, University of Toronto, National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation and and 2 more.
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Several highly potent and broadly neutralizing monoclonal antibodies against HIV have recently been isolated from B cells of infected individuals. However, the effects of these antibodies on the persistent viral reservoirs in HIV-infected individuals receiving antiretroviral therapy (ART) are unknown. We show that several HIV-specific monoclonal antibodies--in particular, PGT121, VRC01, and VRC03--potently inhibited entry into CD4(+) T cells of HIV isolated from the latent viral reservoir of infected individuals whose plasma viremia was well controlled by ART. In addition, we demonstrate that HIV replication in autologous CD4(+) T cells derived from infected individuals receiving ART was profoundly suppressed by three aforementioned and other HIV-specific monoclonal antibodies. These findings have implications for passive immunotherapy as an approach toward controlling plasma viral rebound in patients whose ART is withdrawn.


PubMed | National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation and and Frederick National Laboratory for Cancer Research
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

The adaptive immune system provides critical defense against pathogenic bacteria. Commensal bacteria have begun to receive much attention in recent years, especially in the gut where there is growing evidence of complex interactions with the adaptive immune system. In the present study, we observed that commensal skin bacteria are recognized by major populations of T cells in skin-draining lymph nodes of mice. Recombination activating gene 1 (Rag1)(-/-) mice, which lack adaptive immune cells, contained living skin-derived bacteria and bacterial sequences, especially mycobacteria, in their skin-draining lymph nodes. T cells from skin-draining lymph nodes of normal mice were shown, in vitro, to specifically recognize bacteria of several species that were grown from Rag1(-/-) lymph nodes. T cells from skin-draining lymph nodes, transferred into Rag1(-/-) mice proliferated in skin-draining lymph nodes, expressed a restricted T-cell receptor spectrotype and produced cytokines. Transfer of T cells into Rag1(-/-) mice had the effect of reducing bacterial sequences in skin-draining lymph nodes and in skin itself. Antibacterial effects of transferred T cells were dependent on IFN and IL-17A. These studies suggest a previously unrecognized role for T cells in controlling skin commensal bacteria and provide a mechanism to account for cutaneous infections and mycobacterial infections in T-cell-deficient patients.


News Article | November 15, 2016
Site: www.eurekalert.org

Scientists from the National Institutes of Health have identified an antibody from an HIV-infected person that potently neutralized 98 percent of HIV isolates tested, including 16 of 20 strains resistant to other antibodies of the same class. The remarkable breadth and potency of this antibody, named N6, make it an attractive candidate for further development to potentially treat or prevent HIV infection, say the researchers. The scientists, led by Mark Connors, M.D., of NIH's National Institute of Allergy and Infectious Diseases (NIAID), also tracked the evolution of N6 over time to understand how it developed the ability to potently neutralize nearly all HIV strains. This information will help inform the design of vaccines to elicit such broadly neutralizing antibodies. Identifying broadly neutralizing antibodies against HIV has been difficult because the virus rapidly changes its surface proteins to evade recognition by the immune system. In 2010, scientists at NIAID's Vaccine Research Center (VRC) discovered an antibody called VRC01 that can stop up to 90 percent of HIV strains from infecting human cells. Like VRC01, N6 blocks infection by binding to a part of the HIV envelope called the CD4 binding site, preventing the virus from attaching itself to immune cells. Findings from the current study showed that N6 evolved a unique mode of binding that depends less on a variable area of the HIV envelope known as the V5 region and focuses more on conserved regions, which change relatively little among HIV strains. This allows N6 to tolerate changes in the HIV envelope, including the attachment of sugars in the V5 region, a major mechanism by which HIV develops resistance to other VRC01-class antibodies. The new findings suggest that N6 could pose advantages over VRC01, which currently is being assessed as intravenous infusions in clinical trials to see if it can safely prevent HIV infection in humans. Due to its potency, N6 may offer stronger and more durable prevention and treatment benefits, and researchers may be able to administer it subcutaneously (into the fat under the skin) rather than intravenously. In addition, its ability to neutralize nearly all HIV strains would be advantageous for both prevention and treatment strategies. J Huang, BH Kang, E Ishida, T Zhou et al. Identification of a CD4-binding site antibody to HIV that evolved near-pan neutralization breadth. Immunity DOI: 10.1016/j.immuni.2016.10.027 (2016). NIAID Director Anthony S. Fauci, M.D., is available to comment on the research. Mark Connors, M.D., chief of the HIV-Specific Immunity Section in NIAID's Laboratory of Immunoregulation and the senior author of the paper, also is available. The research team included scientists from NIAID's Laboratory of Immunoregulation and Vaccine Research Center. NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www. .

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