Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated

Authors

Jill Maaske, Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Stephanie Sproule, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Ann R. Falsey, Rochester Regional HealthFollow
Magdalena E. Sobieszczyk, Division of Infectious Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, New York-Presbyterian Columbia University Irving Medical Center, New York, NY, United States.
Anne F. Luetkemeyer, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, CA, United States.
Grant C. Paulsen, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Sharon A. Riddler, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Merlin L. Robb, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
Charlotte-Paige Rolle, Orlando Immunology Center, Orlando, FL, United States.
Beverly E. Sha, Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States.
Tina Tong, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Bahar Ahani, Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Anastasia A. Aksyuk, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Himanshu Bansal, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Timothy Egan, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Brett Jepson, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Marcelino Padilla, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Nirmeshkumar Patel, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Kathryn Shoemaker, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Ann Marie Stanley, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Phillip A. Swanson, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Deidre Wilkins, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Tonya Villafana, Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Justin A. Green, Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
Elizabeth J. Kelly, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.

Department

Infectious Diseases

Document Type

Article

Publication Title

Frontiers in Immunology

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.

First Page

1062067

DOI

10.3389/fimmu.2022.1062067

Volume

13

Publication Date

1-13-2023

PubMed ID

36713413

Recommended Citation

Maaske, J., Sproule, S., Falsey, A. R., Sobieszczyk, M. E., Luetkemeyer, A. F., Paulsen, G. C., Riddler, S. A., Robb, M. L., Rolle, C., Sha, B. E., Tong, T., Ahani, B., Aksyuk, A. A., Bansal, H., Egan, T., Jepson, B., Padilla, M., Patel, N., Shoemaker, K., Stanley, A. M., Swanson, P. A., Wilkins, D., Villafana, T., Green, J. A., & Kelly, E. J. (2023). Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated. Frontiers in Immunology, 13, 1062067. https://doi.org/10.3389/fimmu.2022.1062067