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Link Type
Funded-research
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Article
Publish or Event Date
Link URL
https://news.weill.cornell.edu/news/2023/04/antibody-combination-provided-strong-protection-against-severe-covid-19-in-large
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Weill Cornell Medicine
Short Title
Antibody Combination Provided Strong Protection Against Severe COVID-19 in Large International Trial
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Claudia Wair
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Catey Laube Macdonald

Research Synthetic Nucleic Acid Platforms to Fight HIV

Funding News Editions:
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Apply for a grant to advance synthetic nucleic acid platforms for HIV prevention, treatment, and cure through the new NIAID notice of funding opportunity (NOFO): Synthetic Nucleic Acid Platforms for HIV-1 (SNAPH) (R61/R33, Clinical Trial Not Allowed).

Scientific Synopsis

In your application, describe how you will advance synthetic nucleic acid platforms (SNAP) for the rapid development and iterative testing of active and passive immunization strategies for HIV prevention, treatment, and cure. This includes testing of prophylactic and therapeutic vaccines and the delivery of broadly neutralizing antibodies (bNAb) and bNAb derivatives.

Propose research to apply newly developed immunological tools and expand understanding of the immune response to vaccination at the molecular level. How will you overcome existing challenges to the quality and durability of T-cell and antibody responses to HIV as well as the ability of SNAP to deliver physiologically relevant titers of bNAbs for sustained periods? Describe how you will evaluate the extent to which DNA/RNA technologies can:

  • Be applied to various types of HIV vaccine immunogens and complex regimens.
  • Elicit stronger, broader, and longer-lasting HIV-specific immune responses.
  • Be used in combination with other platforms.
  • Support the delivery of bNAbs or bNAb derivatives for the prevention, treatment, or cure of HIV.

To strengthen the likelihood of successful clinical translation, you must include a translational partner or partners as a significant collaborator in your application. Find further details in the Research Objectives header in Section I of the NOFO, including definitions for translational partner and collaboration, examples of research projects that would be in scope, and nonresponsive scientific areas.

Note that while clinical trials are not allowed for this NOFO, NIAID encourages you to use samples from clinical trials supported by other funding mechanisms. Animal research is allowed, including the use of small animal models and nonhuman primates with HIV, SIV, or SHIV challenges.

Award and Application Specifics

Due to the high-risk, high-impact nature of the research, the SNAPH NOFO uses the R61/R33 phased innovation grant award mechanism:

  • R61 phase. NIAID will provide support for up to 3 years for hypothesis-driven design, optimization, and characterization of SNAP for the delivery of synthetic nucleic acid immunogens, bNAbs, and/or bNAb derivatives.
  • Optional R33 phase. NIAID may choose to provide up to 2 years of subsequent support for additional activities as appropriate. For example, NIAID may support work to test your SNAP delivery approach in relevant animal models and evaluate product potential. NIAID will review and negotiate R33 phase milestones before award.

This opportunity has a single due date; be sure to apply by August 2, 2023, at 5 p.m. local time of the applicant organization. Submit your optional Letter of Intent 30 days before you apply.

Well before you apply, we encourage you to reach out to the following NIAID scientific/research program contacts to discuss your project plans:

  • For immunology and design of prophylactic immunomodulators, antibodies, and immunogens: Dr. Angela Malaspina., angela.malaspina@nih.gov or 240-292-6130.
  • For immunology and design of therapeutic immunomodulators, antibodies, and immunogens: Dr. Steve Smiley, stephen.smiley@nih.gov or 240-627-3071.
  • For therapeutic interventions in animal studies: Dr. Brigitte Sanders, brigitte.sanders@nih.gov or 240-627-3209.

Direct your peer review or grants management questions to the relevant contacts in Section VII of the NOFO.

Contact Us

Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.

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AIDS Imaging Research—Integrated Research Facility at Fort Detrick

The AIDS Imaging Research Section (AIRS) leverages preclinical and translational molecular imaging to study the pathogenesis of human immunodeficiency virus (HIV) infection using the simian/simian-human immunodeficiency virus (SIV/SHIV) nonhuman primate model.

Sinu P. John, Ph.D.

Section or Unit Name
Signaling Systems Section
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Section/Unit: Year Established
Section/Unit: Location
NIH Main Campus, Bethesda, MD
This Researcher/Clinician’s Person Page
Sinu P. John, Ph.D.
Parent Lab/Program
Laboratory of Immune System Biology
Program Description

Our research focuses primarily on identification of cell intrinsic factors (protein coding and non-coding genes) associated with regulation of macrophage signaling. We use high throughput genome-wide techniques such as RNAi screening, CRISPR screening, RNA-seq, ATAC-seq, etc. to identify and characterize the genes and gene-regulatory mechanisms that modulate the immune response in macrophage cells. In addition, we study the role of various external factors (environmental pollutants, drugs, diet, etc.) that modulate the immune response in macrophages with an emphasis to develop therapeutic candidates for the treatment of infectious and immune diseases. We use both bacterial and several emerging viral models such as HIV, Influenza, SARS-CoV-2, etc. to study the impact of immune regulation by various intrinsic and external factors.

Selected Publications

John SP, Singh A, Sun J, Pierre MJ, Alsalih L, Lipsey C, Traore Z, Balcom-Luker S, Bradfield CJ, Song J, Markowitz TE, Smelkinson M, Ferrer M, Fraser IDC. Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection. Cell Rep. 2022 Oct 4;41(1):111441.

John SP, Sun J, Carlson RJ, Cao B, Bradfield CJ, Song J, Smelkinson M, Fraser IDC. IFIT1 Exerts Opposing Regulatory Effects on the Inflammatory and Interferon Gene Programs in LPS-Activated Human Macrophages. Cell Rep. 2018 Oct 2;25(1):95-106.e6.

John SP, Chin CR, Perreira JM, Feeley EM, Aker AM, Savidis G, Smith SE, Elia AE, Everitt AR, Vora M, Pertel T, Elledge SJ, Kellam P, Brass AL. The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. J Virol. 2013 Jul;87(14):7837-52.

Zhu J, Gaiha GD, John SP, Pertel T, Chin CR, Gao G, Qu H, Walker BD, Elledge SJ, Brass AL. Reactivation of latent HIV-1 by inhibition of BRD4. Cell Rep. 2012 Oct 25;2(4):807-16.

Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB; GenISIS Investigators; MOSAIC Investigators; Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012 Mar 25;484(7395):519-23.

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009 Dec 24;139(7):1243-54.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Genes and epigenetic states modulating macrophage signaling and function
  • Identification and characterization of trained immunity stimuli
  • Applications of trained immunity in infectious and immune disease
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