# NK cell memory subsets and their impact on HIV disease progression and vaccination

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $219,278

## Abstract

PROJECT SUMMARY/ABSTRACT:
Despite the many options for HIV treatment and prevention, an efficacious and safe vaccine remains a key
component in efforts to end the pandemic. Natural killer (NK) cells play a crucial role in anti-viral immune
responses. Not only have they have been shown to play a critical role in host protection through direct targeting
of virally infected cells and also via NK-mediated antibody dependent cellular cytotoxicity. However, recent
studies suggest a more encompassing role for NK cells since they can develop into long-lived memory cells and
acquire antigen specificity. Thus, there is a need to elucidate the cellular and molecular mechanisms regulating
NK cell responses to natural HIV infection and HIV vaccination. The long-term goal of our research is to devise
safe and effective vaccine strategies to counter this viral pandemic. To achieve this, we have focused on
understanding the mechanisms that mobilize NK cells, with particular attention to inducing NK cell cytotoxicity.
The objective of this proposal is to identify qualitative and quantitative features of NK cell activation and
differentiation inducted by HIV natural infection and Adenovirus (Ad)-vectored-based vaccination. The
overarching hypothesis is that both natural HIV infection and Ad-vectored HIV vaccination will induce the
activation and maturation of NK cells and subsequent development of memory NK cells. Our rationale is that
understanding the mechanisms regulating NK cell activation and functionality, in addition to the cellular and
molecular mechanisms of antibody-mediated NK cell functions, in response to both natural HIV infection and
vaccination, will be beneficial for establishing translational interventions against HIV and other viral infections.
Our specific aims will test the following: Aim 1: Differentiate memory NK cell subsets and their potential impact
on HIV disease progression and response to Ad26.Mos.HIV vaccination; and Aim 2: Map and compare memory
NK cell epigenetic signatures in response to HIV natural infection and Ad26.Mos.HIV vaccination. Upon
conclusion, our analysis will help to fill the current knowledge gap regarding NK cell memory development in
responses to both natural HIV infection and HIV vaccination. This knowledge is important because we expect it
to identify novel aspects of the immune system we can modulate to our advantage against viral pathogens, and
ultimately use NK cells as part of future effective therapeutic vaccine strategies.

## Key facts

- **NIH application ID:** 10534505
- **Project number:** 1R21AI172041-01
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Kawthar Machmach leggat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $219,278
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534505

## Citation

> US National Institutes of Health, RePORTER application 10534505, NK cell memory subsets and their impact on HIV disease progression and vaccination (1R21AI172041-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10534505. Licensed CC0.

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