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

https://doi.org/10.1016/j.xcrm.2022.100679Get rights and content
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Highlights

  • Vaccine boost substantially increases Omicron neutralizing antibody titers

  • Boosted neutralization titers to Omicron but not prototypic D614G decline rapidly

  • Ad26.COV2.S is better as prime or boost with mRNA vaccines than as homologous boost

  • Omicron sublineages exhibit 5–12 times reduced neutralization by mRNA-1273 boost sera

Summary

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.

Key Words

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

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24

These authors contributed equally

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