# Antigen-Specific NK Cell Memory Against SIV and HIV Vaccines

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $839,952

## Abstract

Natural killer (NK) cells provide rapid early responses to viral infections and thus can contribute
substantially to disease modulation and vaccine protection. Traditionally, NK cells have been
considered to be nonspecific components of innate immunity, but recent studies in mice have
shown that NK cells can also demonstrate features of antigen-specific memory. Until recently it
was unclear whether this phenomenon might exist in primates, but our preliminary data
demonstrates for the first time evidence of antigen-specific NK cell memory in any
primate species. As compared with NK cells from uninfected macaques, splenic and hepatic
NK cells from simian immunodeficiency virus (SIV)-infected animals were highly reactive to
Gag- and Env-pulsed dendritic cells (DCs) but not to mock-pulsed DCs or mis-matched antigen
controls. Similar Gag-specific NK cell responses were found in treated and untreated HIV-1-
infected patients. Interestingly, memory NK cell responses in peripheral blood were low
compared to distal sites, suggesting memory NK cells reside predominantly in tissues. We also
found NK cell memory responses in rhesus macaques for over 5 years following vaccination
with recombinant Ad26 vectors expressing HIV-1 Env or SIV Gag indicating antigen-specific
NK cell memory is durable and does not require ongoing antigenic stimulation. The
longevity, functionality, and specificity of memory NK cell responses in primates suggest their
functional relevance and their potential importance against HIV-1 and other pathogens. In this
new proposal we will address major deficits to this new field of study including identifying the
mechanisms, kinetics, distribution, and efficacy of these responses using state-of-the-art
techniques. We will evaluate the overarching hypothesis that memory NK cell responses
elicited against SIV/HIV and adenovirus vaccine vectors are long-lived even in the absence of
replicating virus and can be mobilized to engage and lyse virus-infected cells in an antigen-
specific manner. We will evaluate this hypothesis with three focused Specific Aims: (1) Evaluate
mobilization and recall of memory NK cells elicited against HIV and SIV vaccine antigens
in humans and macaques; (2) Evaluate mobilization and maintenance of memory NK
cells after SIV challenge in vaccinated and unvaccinated macaques; and (3) Explore
cellular and molecular mechanisms of memory NK cell recognition and specificity.

## Key facts

- **NIH application ID:** 9966875
- **Project number:** 5R01AI120828-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Roger Keith Reeves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $839,952
- **Award type:** 5
- **Project period:** 2017-07-25 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966875

## Citation

> US National Institutes of Health, RePORTER application 9966875, Antigen-Specific NK Cell Memory Against SIV and HIV Vaccines (5R01AI120828-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966875. Licensed CC0.

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