RT Journal Article
SR Electronic
T1 Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.14.480449
DO 10.1101/2022.02.14.480449
A1 Zhenhao Fang
A1 Lei Peng
A1 Renata Filler
A1 Kazushi Suzuki
A1 Andrew McNamara
A1 Qianqian Lin
A1 Paul A. Renauer
A1 Luojia Yang
A1 Bridget Menasche
A1 Angie Sanchez
A1 Ping Ren
A1 Qiancheng Xiong
A1 Madison Strine
A1 Paul Clark
A1 Chenxiang Lin
A1 Albert I. Ko
A1 Nathan D. Grubaugh
A1 Craig B. Wilen
A1 Sidi Chen
YR 2022
UL http://biorxiv.org/content/early/2022/02/28/2022.02.14.480449.abstract
AB The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high transmissibility and recently swept the globe. Due to the extensive number of mutations, this variant has high level of immune evasion, which drastically reduced the efficacy of existing antibodies and vaccines. Thus, it is important to test an Omicron-specific vaccine, evaluate its immune response against Omicron and other variants, and compare its immunogenicity as boosters with existing vaccine designed against the reference wildtype virus (WT). Here, we generated an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and tested its activity in animals, both alone and as a heterologous booster to existing WT mRNA vaccine. Our Omicron-specific LNP-mRNA vaccine elicited strong and specific antibody response in vaccination-naïve mice. Mice that received two-dose WT LNP-mRNA, the one mimicking the commonly used Pfizer/Moderna mRNA vaccine, showed a >40-fold reduction in neutralization potency against Omicron variant than that against WT two weeks post second dose, which further reduced to background level >3 months post second dose. As a booster shot for two-dose WT mRNA vaccinated mice, a single dose of either a homologous booster with WT LNP-mRNA or a heterologous booster with Omicron LNP-mRNA restored the waning antibody response against Omicron, with over 40-fold increase at two weeks post injection as compared to right before booster. Interestingly, the heterologous Omicron LNP-mRNA booster elicited neutralizing titers 10-20 fold higher than the homologous WT booster against the Omicron variant, with comparable titers against the Delta variant. All three types of vaccination, including Omicron mRNA alone, WT mRNA homologous booster, and Omicron heterologous booster, elicited broad binding antibody responses against SARS-CoV-2 WA-1, Beta, and Delta variants, as well as other Betacoronavirus species such as SARS-CoV, but not Middle East respiratory syndrome coronavirus (MERS-CoV). These data provided direct proof-of-concept assessments of an Omicron-specific mRNA vaccination in vivo, both alone and as a heterologous booster to the existing widely-used WT mRNA vaccine form.Competing Interest StatementThe authors have declared no competing interest.