# Innate and adaptive defenses against SARS-COV-2 in the oral cavity during acute unvaccinated and breakthrough infections

> **NIH NIH R56** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $483,000

## Abstract

Background. Vaccines against SARS-CoV-2 (CoV-2) do not prevent infection and subsequent
transmission. Strong evidence now implicates the oral cavity as a primary site of acute CoV-2
infection It is therefore incumbent upon us to search for evidence as to why primary mucosal
sites, such as the tongue, remain vulnerable to CoV-2 infection despite vaccination.
Our goal. Immune responses are both innate, which are not specific to an invading pathogen,
and adaptive, which are specific antibody responses. We hypothesize that interrogating oral
epithelial cells and saliva collected from CoV-2 acutely infected unvaccinated and
breakthrough-infected subjects will reveal early and specific innate and adaptive immune
responses that vary with viral load, viral variants, viral clearance, and patient sex and age.
We will collect samples at two time points from acutely infected unvaccinated participants; one
within 7 days and the second within 14 days of testing positive. We will evaluate the relationship
among measures of oral mucosal viral replication, innate and adaptive factors from salivary,
cytological, and serological sources and determine their associations with quantitative viral
measures in the oral mucosa. Innate factors to be analyzed in the saliva include, but not limited
to, cytokines, antimicrobial peptides, interferons (IFN) and secretory IgA that are correlated with
early infection events. To cross validate our results we will also characterize viral strains and
develop novel PCR-based assays for intracellular CoV-2 RNA. Studies will include single cell
RNA sequencing to analyze virus-induced gene expression changes in infected and bystander
cells from the tongue. Full genome sequencing will be used to determine if viral variants are
present and correlate oral immune profiles with variants. Finally we will develop digital PCR
assays to selectively amplify sub genomic CoV-2 RNA as a rapid measure of infected cells. Once
this baseline information is established, we will compare the adaptive and innate oral immune
factors of CoV-2 vaccinated and breakthrough study participants, respectively, to the oral immune
responses in natural infection.
How will we advance the field? This study will allow us to chronicle for the first time the impact
of vaccination on oral immune responses of healthy individuals and compare them to immune
responses from COVID-19-exposed individuals. We anticipate that our integrated accounting of
the oral immune responses during the natural history of SARS-CoV-2 infections will provide an
invaluable reference data set for patients, healthcare professionals and those measuring the
efficacy of antiviral treatments, immunotherapies and vaccines.

## Key facts

- **NIH application ID:** 10667248
- **Project number:** 1R56DE031279-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** JEFFREY M. JACOBSON
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $483,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667248

## Citation

> US National Institutes of Health, RePORTER application 10667248, Innate and adaptive defenses against SARS-COV-2 in the oral cavity during acute unvaccinated and breakthrough infections (1R56DE031279-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10667248. Licensed CC0.

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