Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), through the National Institute of Allergy and Infectious Diseases (NIAID), issued a funding opportunity titled "Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)" to support research into the mechanisms of HIV-1 envelope (Env) protein expression on infected cells and the development of novel biologics to eliminate these cells. HIV-1 Env is a critical component of the virus's ability to evade immune detection and clearance. This notice of funding opportunity (NOFO) supported both basic and translational research aimed at improving the recognition and elimination of Env-expressing cells, a fundamental challenge in curing HIV. The NIH’s purpose behind this initiative is to understand the biology of the Env protein as expressed on the surface of HIV-1-infected cells, particularly under suppressive antiretroviral therapy. The funding aims to drive innovations in biologics—such as engineered antibodies, CAR T/NK cells, and T/NK cell engagers—that can facilitate cytotoxic immune synapses and effectively target cells expressing even low levels of Env. A deeper understanding of viral-host interactions influencing Env expression is crucial for developing curative strategies. This program encourages projects that apply emerging technologies, including live cell imaging and in situ structural protein analysis, to advance the field. Allowable uses of the funds included conducting research on cellular pathways regulating Env expression, identifying host factors that influence its cell surface presentation, exploring small-molecule approaches to enhance Env visibility, and designing biologics with improved killing efficiency. However, applications focused solely on transcriptional regulation of Env, latency reversal agents, or discovery of new broadly neutralizing antibodies (bnAbs) were considered non-responsive and thus not eligible for review. Eligibility was broad, including domestic and foreign academic institutions, nonprofits, for-profit entities including small businesses, tribal organizations, and government bodies. The NOFO welcomed applications from both new and established investigators, including multiple principal investigator arrangements. Applicants needed to register in systems like eRA Commons, SAM, and Grants.gov before applying. Key components of the application included research strategy, letters of support, and a Data Management and Sharing Plan. Applications proposing studies in nonhuman primates (NHPs) were required to document the availability of animals and relevant resources. This NOFO followed NIH's standard AIDS-related application cycle. While no specific award floor or ceiling was defined, budgets were expected to match project needs, and the maximum project period was five years. Cost sharing was not required. Applications were submitted via NIH ASSIST or Grants.gov. Applications underwent a rigorous peer review process that emphasized significance, innovation, feasibility, and investigator qualifications. Projects were evaluated for their potential to enhance the understanding of HIV Env biology and to develop effective Env-targeting therapeutics. The funding opportunity was posted on December 2, 2024, with the earliest application submission date of April 7, 2025. Subsequent AIDS-related deadlines occurred every four months through January 2028. However, this notice expired early on February 19, 2026, as per NIH Notice NOT-AI-26-008. Although officially expired, NIH may still consider late applications on a case-by-case basis under its late submission policies. Questions regarding scientific content could be directed to Dr. Yan Zhou, while administrative or financial inquiries could be addressed to Robert Kirker. This NOFO provided a vital opportunity to support scientific advancements in HIV treatment and cure strategies by targeting viral persistence at the cellular level.

Focus on Env expression pathways and mechanisms of biologic-mediated cell killing; validate in primary models when possible.