Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines

Chieh-Yu Liang, Saravanan Raju, Zhuoming Liu, Yuhao Li, Guha Asthagiri Arunkumar, James Brett Case, Suzanne M. Scheaffer, Seth J. Zost, Cory M. Acreman, Matthew Gagne, Shayne F. Andrew, Deborah Carolina Carvalho dos Anjos, Kathryn E. Foulds, Jason S. McLellan, James E. Crowe, Daniel C. Douek, Sean P. J. Whelan, Sayda M. Elbashir, Darin K. Edwards and Michael S. Diamond ()
Additional contact information
Chieh-Yu Liang: Washington University School of Medicine
Saravanan Raju: Washington University School of Medicine
Zhuoming Liu: Washington University School of Medicine
Yuhao Li: Washington University School of Medicine
Guha Asthagiri Arunkumar: Moderna, Inc.
James Brett Case: Washington University School of Medicine
Suzanne M. Scheaffer: Washington University School of Medicine
Seth J. Zost: Vanderbilt University Medical Center
Cory M. Acreman: The University of Texas at Austin
Matthew Gagne: National Institutes of Health
Shayne F. Andrew: National Institutes of Health
Deborah Carolina Carvalho dos Anjos: Washington University School of Medicine
Kathryn E. Foulds: National Institutes of Health
Jason S. McLellan: The University of Texas at Austin
James E. Crowe: Vanderbilt University Medical Center
Daniel C. Douek: National Institutes of Health
Sean P. J. Whelan: Washington University School of Medicine
Sayda M. Elbashir: Moderna, Inc.
Darin K. Edwards: Moderna, Inc.
Michael S. Diamond: Washington University School of Medicine

Nature, 2024, vol. 630, issue 8018, 950-960

Abstract: Abstract Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07539-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:630:y:2024:i:8018:d:10.1038_s41586-024-07539-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07539-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().