Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

the DMID 21-0012 Study Group

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

Original languageEnglish (US)
Article number100679
JournalCell Reports Medicine
Issue number7
StatePublished - Jul 19 2022


  • BA.2.12.1
  • BA.4/BA.5
  • COVID-19
  • Omicron variant
  • SARS-CoV-2
  • booster
  • mRNA vaccine
  • neutralizing antibody
  • recombinant adenovirus vaccine
  • sublineage

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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