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. 2022 Oct 11;8:108. doi: 10.1038/s41421-022-00473-4

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Vaccine design of Omicron BA.2 and Delta variant-specific LNP-mRNA based on BA.2 and Delta spike mutations. Unique spike mutations on BA.2.12.1, BA.2.75, and BA.5 (not included in LNP-mRNA) are colored in orange, green, and red. b Distribution of BA.2 (purple), BA.2.12.1(orange), BA.2.75 (green), and BA.5 (red) mutations in one protomer of Omicron spike trimer (PDB: 7T9K). c Delta- and BA.2-specific monovalent or bivalent LNP-mRNA boosters improved antibody response of WT-vaccinated mice to Omicron BA.2, BA.2.12.1, and BA.4/5 subvariants. Comparison of binding antibody titers against BA.2, BA.2.12.1, and BA.4/5 spike RBD and ECD before (D28) and after (D42) receiving 1.5 µg WT-, Delta-, BA.2-specific monovalent or bivalent (1.5 µg Delta + 1.5 µg BA.2) LNP-mRNA boosters. Antibody titers were quantified by area under curves (AUC) of ELISA response curves in Supplementary Figs. S1 and S2. Blood samples were collected in mice immunized with two doses of 1.5 µg WT LNP-mRNA followed by 1.5 µg WT-, Delta-, BA.2-specific monovalent or Delta & BA.2 bivalent boosters (n = 6 in each group). d Neutralization of Omicron BA.2, BA.2.12.1, BA.2.75, and BA.5 pseudovirus by plasma of mice before (D28) and after (D42) vaccination with WT-, Delta-, BA.2-specific monovalent or Delta & BA.2 bivalent boosters. Six samples collected on day 0 were included and compared to both D28 and D42 datasets. e Neutralization of Omicron BA.2.12.1 and BA.5 authentic virus by plasma of mice before (D28) and after (D42) vaccination with WT-, Delta-, BA.2-specific monovalent or Delta & BA.2 bivalent boosters. Six samples collected on day 0 were included and compared to both D28 and D42 datasets. The authentic virus neutralization assay was blinded. Titer ratios before and after receiving boosters (D42/D28 ratios) were shown in Fig. 1c‒e. Titers in Fig. d, e are log₁₀ transformed. Statistical analysis details can be found in supplementary methods.