Its case doubling time, every 3–4 days, is faster than previous waves 7, hinting its increased intrinsic transmissibility and/or immune evasion. Omicron variant drove the fourth “wave” of Coronavirus Disease 2019 (COVID-19) in South Africa 6 and around the world 7. Similarly in January 2022, Omicron variant has dominated newly diagnosed cases in many states of the US (SARS-CoV-2 Omicron variant: statistics), Canada (Tracking variants of the novel coronavirus in Canada), and UK (Omicron cases tracker by Newsnodes). Population-level data indicated that Omicron has become the dominant variant in South Africa in mid-November 5, only one week after the first traceable case. Two days after its initial report to World Health Organization (WHO), Omicron was designated as a variant of concern (VoC) by WHO on November 26 (Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. The Omicron variant was associated with increased risk of reinfection according to a population-level evidence in South Africa 4. Since its first identification in specimen collected in November 2021 1, the Omicron variant (lineage B.1.1.529) of SARS-CoV-2 has rapidly spread across the globe (Omicron cases tracker by Newsnodes Tracking Omicron variant, GISAID) 2, 3. These data provide direct assessments of an Omicron-specific mRNA vaccination in vivo, both alone and as a heterologous booster to WT mRNA vaccine. 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. 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. 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.
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. Our Omicron-specific LNP-mRNA vaccine elicits strong antibody response in vaccination-naïve mice. 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. The Omicron variant of SARS-CoV-2 recently swept the globe and showed high level of immune evasion.
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