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Immune Correlate + Guided Design of Monoclonal Therapeutics for HIV Remission

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[Technical Report, Annual Report]

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Current HIV-specific broadly neutralizing antibodies bNAbs, selected for their ability to recognize the virus itself, fail to sufficiently kill infected cells and have only had a very modest impact on the HIV reservoir size in humans. Spontaneous control of viral rebound does infrequently occur during natural infection post-treatment controllers and seems to require specific functional antibody profiles with unique antigen specificities. These antibodies shall be identified and extracted from individuals who are undergoing antiretroviral treatment interruption and be functionally optimized to enhance the rapid and highly effective deletion of virally infected cells with the goal to develop anti-reservoir monoclonals that may be used as stand-alone therapeutics. In three aims, this project will define the correlates of humoral immunity that track with viral remission following treatment interruption followed by development of a library of and functionally enhanced novel monoclonal antibodies poised to recognize and kill reactivated latently HIV infected cells as novel therapeutics for HIV cure strategies. From existing sample banks The Thai Red Cross AIDS Research Centre and United States Military HIV Research Program, Walter Reed Army Institute of Research we selected individuals who controlled or did not control viral rebound after antiretroviral treatment interruption. To define the antigen-specific titer characteristics, an array of different HIV antigens was used to measure the antigen-specific antibody isotype and IgGsub class titer in all available patients and the most relevant and targeted antigens for the functional assays were identified. While patients that initiated treatment during the chronic phase of infection developed a robust humoral immune response against the virus, early antiretroviral treatment during the acute phase of infection abolished or at least dampened such a response.

Subject Categories:

  • Microbiology
  • Pharmacology
  • Medicine and Medical Research

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[A, Approved For Public Release]