An mRNA vaccine candidate encoding H5HA clade 2.3.4.4b protects mice from clade 2.3.2.1a virus infection

Shiho Chiba^{1

2

3}, Maki Kiso^{1

3}, Shinya Yamada⁴, Kazuhiko Someya⁴, Yoshikuni Onodera⁴, Aya Yamaguchi⁴, Satoko Matsunaga⁴, Ryuta Uraki^{1

3

5}, Kiyoko Iwatsuki-Horimoto^{1

3}, Seiya Yamayoshi^{1

3

5}, Fumihiko Takeshita⁴, Yoshihiro Kawaoka^{6

7

8

9}

Affiliations

¹ Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Tokyo, 108-8639, Japan.
² Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711, USA.
³ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
⁴ Vaccine Research Laboratories, Research Function, R&D Division, Daiichi Sankyo Co., Ltd, Tokyo, 134-0081, Japan.
⁵ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan.
⁶ Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁷ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711, USA. yoshihiro.kawaoka@wisc.edu.
⁸ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁹ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.

PMID: 39402112
PMCID: PMC11473758
DOI: 10.1038/s41541-024-00988-9

An mRNA vaccine candidate encoding H5HA clade 2.3.4.4b protects mice from clade 2.3.2.1a virus infection

Shiho Chiba et al. NPJ Vaccines. 2024.

. 2024 Oct 14;9(1):189.

doi: 10.1038/s41541-024-00988-9.

Authors

Affiliations

¹ Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Tokyo, 108-8639, Japan.
² Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711, USA.
³ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
⁴ Vaccine Research Laboratories, Research Function, R&D Division, Daiichi Sankyo Co., Ltd, Tokyo, 134-0081, Japan.
⁵ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan.
⁶ Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁷ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53711, USA. yoshihiro.kawaoka@wisc.edu.
⁸ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁹ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.

PMID: 39402112
PMCID: PMC11473758
DOI: 10.1038/s41541-024-00988-9

Abstract

Highly pathogenic avian influenza (HPAI) H5 viruses from different clades have been circulating globally, threatening wild/domestic birds and mammals. Given frequent spillovers and high mortality among mammals, coupled with our inability to predict which clade of H5 virus has pandemic potential, cross-clade protective HPAI H5 vaccines are urgently needed. Here, we demonstrate the applicability of a lipid nanoparticle-based mRNA vaccine modality to induce cross-protective immunity against lethal HPAI virus infection.

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Conflict of interest statement

S.Y., K.S., Y.O., A.Y., T.M., and F.T. are employees of Daiichi Sankyo Co., Ltd. Y.K. has received unrelated funding support from FUJIFILM Toyama Chemical Co., Ltd.; TAUNS Laboratories, Inc.; Shionogi & Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; KM Biologics Co., Ltd.; Kyoritsu Seiyaku Corporation; Shinwa Corporation; and Fujirebio Diagnostics. Y.K. is also a co-founder of FluGen, Inc. Y.K. is supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP24wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP243fa627001) from Japan Agency for Medical Research and Development (AMED). Y.K. and Daiichi Sankyo Co., Ltd. are also supported by the Program on R&D of new generation vaccine including new modality application (JP243fa827010) from AMED. All other authors declare no competing interests.

Figures

**Fig. 1. Immunogenicity of LNP-mRNA-H5HA vaccine in mice.**
a Timeline of mouse immunization. Groups of BALB/c mice (7-wk-old females; N = 5/group) were intramuscularly (i.m.) mock-vaccinated or vaccinated with 1 or 10 μg of DS8390 by using a prime & boost regimen. Two weeks after the boost immunization, serum was collected and single cell suspensions (splenocytes) were prepared from spleens of individual animals. Binding antibody titers against the homologous ch/Ghana HA (b) or heterologous India/S4571 HA (c) in sera were analyzed in an ELISA. Area under the curve (AUC) values for individual animals were plotted. Bars show the median of the groups. Splenocytes (2 × 10⁵ live cells/well) were stimulated with 3 μg of the homologous ch/Ghana HA (d) or heterologous India/S4571 HA protein (e) at 37 °C for 3 days. IFN-γ-secreting cells were detected by use of an ELISpot assay. Statistical analyses were performed by use of a one-way analysis of variance (ANOVA) and corrected for multi-group comparisons by using Dunnett’s test. (*P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001. n.s., not significant).

**Fig. 2. Protective efficacy of LNP-mRNA-H5HA vaccine against homologous or heterologous virus challenge.**
a Timeline of the virus challenge study. Groups of BALB/c mice (7-wk-old females; N = 5/group) were intramuscularly (i.m.) mock-vaccinated or vaccinated with 1 or 10 μg of DS8390 by using a prime & boost regimen. Pre-challenge sera collected 2 wks post-boost were analyzed in an ELISA (Supplementary Fig. 2) and a neutralization assay (Supplementary Table 1). At 3 wks post-boost immunization, the animals were intranasally (i.n.) challenged with 10 MLD₅₀ of homologous A/chicken/Ghana/AVL-76321VIR7050-39/2021 (ch/Ghana; 6.1 × 10²pfu/animal) virus (b, c) or heterologous A/India/SARI-4571/2021 (India/S4571; 3.2 × 10²pfu/animal) virus (d, e). Survival rate (b, d) and body weight change (c, e) were monitored for 14 days (% compared to Day 0; mean + SD).

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References

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An mRNA vaccine candidate encoding H5HA clade 2.3.4.4b protects mice from clade 2.3.2.1a virus infection

Affiliations

An mRNA vaccine candidate encoding H5HA clade 2.3.4.4b protects mice from clade 2.3.2.1a virus infection

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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