AUTHOR=Maaske Jill , Sproule Stephanie , Falsey Ann R. , Sobieszczyk Magdalena E. , Luetkemeyer Anne F. , Paulsen Grant C. , Riddler Sharon A. , Robb Merlin L. , Rolle Charlotte-Paige , Sha Beverly E. , Tong Tina , Ahani Bahar , Aksyuk Anastasia A. , Bansal Himanshu , Egan Timothy , Jepson Brett , Padilla Marcelino , Patel Nirmeshkumar , Shoemaker Kathryn , Stanley Ann Marie , Swanson Phillip A. , Wilkins Deidre , Villafana Tonya , Green Justin A. , Kelly Elizabeth J. TITLE=Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1062067 DOI=10.3389/fimmu.2022.1062067 ISSN=1664-3224 ABSTRACT=Background

Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals.

Methods

To explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746).

Results

We observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints.

Conclusion

Robust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic.