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. 2024 Nov:109:105408.
doi: 10.1016/j.ebiom.2024.105408. Epub 2024 Oct 30.

Protective effects of an mRNA vaccine candidate encoding H5HA clade 2.3.4.4b against the newly emerged dairy cattle H5N1 virus

Shiho Chiba  1 , Maki Kiso  2 , Shinya Yamada  3 , Kazuhiko Someya  3 , Yoshikuni Onodera  3 , Aya Yamaguchi  3 , Satoko Matsunaga  3 , Nao Jounai  3 , Seiya Yamayoshi  4 , Fumihiko Takeshita  3 , Yoshihiro Kawaoka  5
Affiliations

Protective effects of an mRNA vaccine candidate encoding H5HA clade 2.3.4.4b against the newly emerged dairy cattle H5N1 virus

Shiho Chiba et al. EBioMedicine. 2024 Nov.
No abstract available

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Conflict of interest statement

Declaration of interests Sh,Y., K.S., Y.O., A.Y., S.M., N.J., 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.

Figures

Fig. 1
Fig. 1
Immunogenicity and protective efficacy of LNP-mRNA-H5HA vaccine against cattle H5N1 virus in mice. (A)Timeline of mouse immunization. BALB/c mice (7-wk-old females; N = 5/group) were intramuscularly (i.m.) mock-vaccinated or vaccinated with 1 or 10 μg of LNP-mRNA-H5HA (chicken/Ghana) vaccine by using a prime & boost regimen. (B and C) Pre-challenge sera were collected at 6 wks post-boost immunization, and binding IgG antibody titres against HA from the homologous A/chicken/Ghana/AVL-76321VIR7050-39/2021 virus (chicken/Ghana; B) or HA from A/bovine/New Mexico/A240920343-93/2024 virus (bovine/NM93; C) in sera were analysed in an ELISA. Area under the curve (AUC) values for individual animals were plotted. Bars show the median of the groups. (D and E) At 7 wks post-boost immunization, the animals were intranasally (i.n.) challenged with 10 mouse median lethal dose (MLD50) of A/dairy cattle/Texas/24-008749-001-original/2024 virus (cattle/TX; H5N1, clade 2.3.4.4 b; 1.5 × 101 pfu/animal). Survival rate (D) and body weight change (E) were monitored for 12 days (% compared to Day 0; mean +SD). 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). (F) Timeline of mouse immunization for virus titration in organs. Groups of animals immunized twice with a 2-wk interval were challenged with 10 MLD50 of cattle/TX virus at 3 wks post-boost. On Days 3 and 5 post–challenge, lungs (G), nasal turbinates (H), and brains (I) were harvested for infectious virus titration in plaque assays. The detection limit of the plaque assay (1 log10 pfu/g) is shown as a dashed line. Bars show the median of the groups. Statistical differences compared with the mock-vaccinated groups were analyzed by using the Kruskal–Wallis test, and corrected by using Dunn's multiple comparison test (∗P < 0.05; ∗∗P < 0.01). The bovine/NM93 and cattle/TX viruses differ by one amino acid in HA at position 320 (H5 numbering; see Supplementary Figure).
Fig. 1
Fig. 1
Immunogenicity and protective efficacy of LNP-mRNA-H5HA vaccine against cattle H5N1 virus in mice. (A)Timeline of mouse immunization. BALB/c mice (7-wk-old females; N = 5/group) were intramuscularly (i.m.) mock-vaccinated or vaccinated with 1 or 10 μg of LNP-mRNA-H5HA (chicken/Ghana) vaccine by using a prime & boost regimen. (B and C) Pre-challenge sera were collected at 6 wks post-boost immunization, and binding IgG antibody titres against HA from the homologous A/chicken/Ghana/AVL-76321VIR7050-39/2021 virus (chicken/Ghana; B) or HA from A/bovine/New Mexico/A240920343-93/2024 virus (bovine/NM93; C) in sera were analysed in an ELISA. Area under the curve (AUC) values for individual animals were plotted. Bars show the median of the groups. (D and E) At 7 wks post-boost immunization, the animals were intranasally (i.n.) challenged with 10 mouse median lethal dose (MLD50) of A/dairy cattle/Texas/24-008749-001-original/2024 virus (cattle/TX; H5N1, clade 2.3.4.4 b; 1.5 × 101 pfu/animal). Survival rate (D) and body weight change (E) were monitored for 12 days (% compared to Day 0; mean +SD). 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). (F) Timeline of mouse immunization for virus titration in organs. Groups of animals immunized twice with a 2-wk interval were challenged with 10 MLD50 of cattle/TX virus at 3 wks post-boost. On Days 3 and 5 post–challenge, lungs (G), nasal turbinates (H), and brains (I) were harvested for infectious virus titration in plaque assays. The detection limit of the plaque assay (1 log10 pfu/g) is shown as a dashed line. Bars show the median of the groups. Statistical differences compared with the mock-vaccinated groups were analyzed by using the Kruskal–Wallis test, and corrected by using Dunn's multiple comparison test (∗P < 0.05; ∗∗P < 0.01). The bovine/NM93 and cattle/TX viruses differ by one amino acid in HA at position 320 (H5 numbering; see Supplementary Figure).
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References

    1. CDC confirms three human cases of H5 bird flu among Colorado poultry workers. 2024. https://www.cdc.gov/media/releases/2024/s0725-three-human-cases-of-h5-bi...
    1. CDC confirms second human H5 bird flu case in Michigan; third case tied to dairy outbreak. 2024. https://www.cdc.gov/media/releases/2024/p0530-h5-human-case-michigan.html
    1. Highly pathogenic avian influenza A (H5N1) virus infection reported in a person in the U.S. 2024. https://www.cdc.gov/media/releases/2024/p0401-avian-flu.html
    1. Federal and State Veterinary Public health agencies share update on HPAI detection in Kansas. Texas Dairy Herds. 2024 https://www.aphis.usda.gov/news/agency-announcements/federal-state-veter...
    1. CDC confirms human cases of H5 bird flu among Colorado poultry workers. 2024. https://www.cdc.gov/media/releases/2024/p-0715-confirm-h5.html

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