AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection

Authors

Anastasia A. Aksyuk, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Himanshu Bansal, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Deidre Wilkins, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Ann Marie Stanley, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Stephanie Sproule, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Jill Maaske, Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Satya Sanikommui, Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
William R. Hartman, Department of Anesthesiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USA.
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 10032, USA.
Ann R. Falsey, Rochester Regional HealthFollow
Elizabeth J. Kelly, Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.

Department

Infectious Diseases

Document Type

Article

Publication Title

Cell Reports. Medicine

Abstract

The nasal mucosa is an important initial site of host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, intramuscularly administered vaccines typically do not achieve high antibody titers in the nasal mucosa. We measure anti-SARS-CoV-2 spike immunoglobulin G (IgG) and IgA in nasal epithelial lining fluid (NELF) following intramuscular vaccination of 3,058 participants from the immunogenicity substudy of a phase 3, double-blind, placebo-controlled study of AZD1222 vaccination (ClinicalTrials.gov: NCT04516746). IgG is detected in NELF collected 14 days following the first AZD1222 vaccination. IgG levels increase with a second vaccination and exceed pre-existing levels in baseline-SARS-CoV-2-seropositive participants. Nasal IgG responses are durable and display strong correlations with serum IgG, suggesting serum-to-NELF transudation. AZD1222 induces short-lived increases to pre-existing nasal IgA levels in baseline-seropositive vaccinees. Vaccinees display a robust recall IgG response upon breakthrough infection, with overall magnitudes unaffected by time between vaccination and illness. Mucosal responses correlate with reduced viral loads and shorter durations of viral shedding in saliva.

First Page

100882

DOI

10.1016/j.xcrm.2022.100882

Volume

4

Issue

1

Publication Date

1-17-2023

PubMed ID

36610390

Recommended Citation

Aksyuk, A. A., Bansal, H., Wilkins, D., Stanley, A. M., Sproule, S., Maaske, J., Sanikommui, S., Hartman, W. R., Sobieszczyk, M. E., Falsey, A. R., & Kelly, E. J. (2023). AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection. Cell Reports. Medicine, 4 (1), 100882. https://doi.org/10.1016/j.xcrm.2022.100882