# SARS-CoV-2-Specific Immune Responses in Vaccination and Infection during the Pandemic in 2020–2022

## TL;DR

This study examines immune responses to SARS-CoV-2 from 2020 to 2022, comparing natural infection and vaccination, and finds that mucosal immunity may offer better protection than current vaccines.

## Contribution

The study highlights the potential of early mucosal immune responses in SARS-CoV-2 infection to provide better protection than intramuscular vaccines.

## Key findings

- mRNA vaccination in 2021 produced higher anti-RBD IgG than natural infection
- third vaccination boosted IgG levels but to a lower extent than the second
- mucosal IgA responses in saliva were temporary and may offer better protection

## Abstract

To gain insight into how immunity develops against SARS-CoV-2 from 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined eight months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after six months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN γ or CD107a were detected only early. Although SARS-CoV-2-specific salivary IgA was undetectable, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Our study, despite having a small sample size, revealed that SARS-CoV-2 infection triggers the expected immune responses against acute viral infections. Moreover, our findings suggest that the temporary mucosal immune responses induced early during infection may provide better protection than the currently available intramuscular vaccines.