Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

Baoling Ying, Suzanne M. Scheaffer, Bradley Whitener, Chieh Yu Liang, Oleksandr Dmytrenko, Samantha Mackin, Kai Wu, Diana Lee, Laura E. Avena, Zhenlu Chong, James Brett Case, Ling Zhi Ma, Thu T.M. Kim, Caralyn E. Sein, Angela Woods, Daniela Montes Berrueta, Gwo Yu Chang, Guillaume Stewart-Jones, Isabella Renzi, Yen Ting LaiAgata Malinowski, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.

Original languageEnglish
Pages (from-to)1572-1587.e11
Issue number9
StatePublished - Apr 28 2022


  • Omicron
  • SARS-CoV-2
  • antibody
  • booster
  • immunity
  • mRNA vaccine
  • mice
  • neutralization
  • pathogenesis


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