SARS-CoV-2 mRNA Vaccines Induce Cross-Reactive Antibodies to NL63 Coronavirus but Do Not Boost Pre-Existing Immunity

Weiyi Tang1, Zi Wei Chang1, Yun Shan Goh1

  • 1A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

Vaccines
|April 23, 2025
PubMed
Abstract

Insights

The Moderna mRNA vaccine generates antibodies that cross-react with the seasonal coronavirus NL63. Pre-existing NL63 immunity does not impact the SARS-CoV-2 vaccine response.

Area of Science:

  • Immunology
  • Virology
  • Vaccinology

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines show high efficacy.
  • Antibody cross-reactivity of these vaccines against common human seasonal coronaviruses, like NL63, is not well understood.
  • The influence of pre-existing immunity to NL63 on SARS-CoV-2 mRNA vaccine effectiveness requires investigation.

Purpose of the Study:

  • To investigate antibody cross-reactivity between SARS-CoV-2 mRNA vaccines and the human seasonal coronavirus NL63.
  • To determine if pre-existing NL63 antibodies affect the immune response to SARS-CoV-2 mRNA vaccination.

Main Methods:

  • Utilized flow cytometry and in vitro neutralization assays.
  • Analyzed serum from SARS-CoV-2 mRNA-vaccinated mice.
  • Examined plasma samples from a cohort of vaccinated humans.

Main Results:

  • The Moderna mRNA-1273 vaccine induced cross-reactive antibodies against NL63.
  • SARS-CoV-2 mRNA vaccination did not enhance pre-existing anti-NL63 antibody levels in humans.
  • Pre-existing NL63 antibody titers did not influence the immunogenicity of SARS-CoV-2 mRNA vaccines.

Conclusions:

  • SARS-CoV-2 mRNA vaccines can elicit antibodies that cross-react with NL63.
  • Pre-existing immunity to NL63 does not significantly alter the immunogenicity of SARS-CoV-2 mRNA vaccines.
  • Findings clarify the interaction between seasonal coronavirus immunity and SARS-CoV-2 mRNA vaccine responses.