Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

Zhenhao Fang, Lei Peng, Renata Filler, Kazushi Suzuki, Andrew McNamara, Qianqian Lin, Paul A. Renauer, Luojia Yang, Bridget Menasche, Angie Sanchez, Ping Ren, Qiancheng Xiong, Madison Strine, Paul Clark, Chenxiang Lin, Albert I. Ko, Nathan D. Grubaugh, Craig B. Wilen () and Sidi Chen ()
Additional contact information
Zhenhao Fang: Yale University School of Medicine
Lei Peng: Yale University School of Medicine
Renata Filler: Yale University
Kazushi Suzuki: Yale University School of Medicine
Andrew McNamara: Yale University
Qianqian Lin: Yale University School of Medicine
Paul A. Renauer: Yale University School of Medicine
Luojia Yang: Yale University School of Medicine
Bridget Menasche: Yale University
Angie Sanchez: Yale University School of Medicine
Ping Ren: Yale University School of Medicine
Qiancheng Xiong: Yale University
Madison Strine: Yale University
Paul Clark: Yale University School of Medicine
Chenxiang Lin: Yale University
Albert I. Ko: Yale School of Public Health
Nathan D. Grubaugh: Yale School of Public Health
Craig B. Wilen: Yale University
Sidi Chen: Yale University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract The Omicron variant of SARS-CoV-2 recently swept the globe and showed high level of immune evasion. Here, we generate an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and test its activity in animals, both alone and as a heterologous booster to WT mRNA vaccine. Our Omicron-specific LNP-mRNA vaccine elicits strong antibody response in vaccination-naïve mice. Mice that received two-dose WT LNP-mRNA show a > 40-fold reduction in neutralization potency against Omicron than WT two weeks post boost, which further reduce to background level after 3 months. The WT or Omicron LNP-mRNA booster increases the waning antibody response of WT LNP-mRNA vaccinated mice against Omicron by 40 fold at two weeks post injection. Interestingly, the heterologous Omicron booster elicits neutralizing titers 10-20 fold higher than the homologous WT booster against Omicron variant, with comparable titers against Delta variant. All three types of vaccination, including Omicron alone, WT booster and Omicron booster, elicit broad binding antibody responses against SARS-CoV-2 WA-1, Beta, Delta variants and SARS-CoV. These data provide direct assessments of an Omicron-specific mRNA vaccination in vivo, both alone and as a heterologous booster to WT mRNA vaccine.

Date: 2022
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DOI: 10.1038/s41467-022-30878-4

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