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Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection

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To identify the key insights or developments described in this article
1 Credit CME

Breakthrough infections after vaccination against SARS-CoV-2 are increasingly reported, possibly due to waning of vaccine-induced antibody levels.1 Moreover, emerging variants of concern with diminished susceptibility to vaccine-induced antibodies are responsible for most new cases.2,3 Studies have focused on determining the rate of vaccine breakthrough based on antibody levels after standard vaccination practices.4,5 We assessed antibody levels and variant cross-neutralization after breakthrough infection.

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Article Information

Corresponding Author: Fikadu G. Tafesse, PhD, Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239 (tafesse@ohsu.edu).

Accepted for Publication: December 3, 2021.

Published Online: December 16, 2021. doi:10.1001/jama.2021.22898

Author Contributions: Dr Tafesse had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bates, McBride, Winders, Curlin, Tafesse.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Bates.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Bates, McBride, Schoen.

Obtained funding: Curlin, Tafesse.

Administrative, technical, or material support: Bates, McBride, Schoen, Curlin, Tafesse.

Supervision: Curlin, Tafesse.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded in part by an unrestricted grant from the M. J. Murdock Charitable Trust, an unrestricted grant from the Oregon Health & Science University (OHSU) Foundation, National Institutes of Health training grant T32HL083808 on Multidisciplinary Research Training in Pulmonary Medicine, and OHSU Innovative IDEA grant 1018784.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We acknowledge the efforts of the OHSU COVID-19 serology research team for their assistance with sample acquisition and data collection. We also want to thank the Oregon SARS-CoV-2 Genome Sequencing Center at OHSU for their help in sequencing our samples, including Xuan Qin, PhD, Brian O’Roak, PhD, Andrew Adey, PhD, and Benjamin Bimber, PhD. None of the above individuals were compensated for their contributions. We are grateful for the Oregon Health & Science University faculty, staff, and patients who contributed to this study.

References
1.
Levin  EG , Lustig  Y , Cohen  C ,  et al.  Waning immune humoral response to BNT162b2 Covid-19 vaccine over 6 months.   N Engl J Med. 2021. doi:10.1056/NEJMoa2114583PubMedGoogle Scholar
2.
Chen  RE , Zhang  X , Case  JB ,  et al.  Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies.   Nat Med. 2021;27(4):717-726. doi:10.1038/s41591-021-01294-wPubMedGoogle ScholarCrossref
3.
Lopez Bernal  J , Andrews  N , Gower  C ,  et al.  Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant.   N Engl J Med. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891PubMedGoogle ScholarCrossref
4.
Bergwerk  M , Gonen  T , Lustig  Y ,  et al.  Covid-19 breakthrough infections in vaccinated health care workers.   N Engl J Med. 2021;385(16):1474-1484. doi:10.1056/NEJMoa2109072PubMedGoogle ScholarCrossref
5.
Chau  NVV , Ngoc  NM , Nguyet  LA ,  et al.  An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam.   EClinicalMedicine. 2021;41:101143. doi:10.1016/j.eclinm.2021.101143PubMedGoogle Scholar
6.
Falsey  AR , Frenck  RW  Jr , Walsh  EE ,  et al.  SARS-CoV-2 neutralization with BNT162b2 vaccine dose 3.   N Engl J Med. 2021;385(17):1627-1629. doi:10.1056/NEJMc2113468PubMedGoogle ScholarCrossref
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