Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza

Nguyen, Bao Linh; Isoda, Norikazu; Hew, Yik Lim; Huynh, Loc Tan; Le, Kien Trung; Shimazu, Yo; Kobayashi, Daiki; Nguyen, Dang Hoang; Nguyen, Tho Dang; Chu, Duc-Huy; Nguyen, Diep Thi; Takeichi, Koki; Nanba, Yuto; Hiono, Takahiro; Sasaki, Takashi; Sakoda, Yoshihiro

doi:10.3390/vaccines14040291

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Open AccessArticle

Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza

by

Bao Linh Nguyen

¹,

Norikazu Isoda

^1,2,3,4,*

,

Yik Lim Hew

¹

,

Loc Tan Huynh

^1,†

,

Kien Trung Le

^1,‡

,

Yo Shimazu

¹

,

Daiki Kobayashi

¹

,

Dang Hoang Nguyen

⁵,

Tho Dang Nguyen

⁵,

Duc-Huy Chu

⁶,

Diep Thi Nguyen

⁶,

Koki Takeichi

⁷,

Yuto Nanba

⁷,

Takahiro Hiono

^1,2,3,4,

Takashi Sasaki

⁷ and

Yoshihiro Sakoda

^1,2,3,4

¹

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Hokkaido, Japan

²

One Health Research Center, Hokkaido University, Sapporo 060-0818, Hokkaido, Japan

³

International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-0818, Hokkaido, Japan

⁴

Hokkaido University Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo 060-0818, Hokkaido, Japan

⁵

National Center for Veterinary Diagnostics No.1, Noi Bai Commune, Hanoi 12206, Vietnam

⁶

Department of Animal Health, Kim Lien Ward, Hanoi 11520, Vietnam

⁷

Kyoto Biken Laboratories, Inc., 16 Nijushi, Makishima-cho, Uji 611-0041, Kyoto, Japan

^*

Author to whom correspondence should be addressed.

^†

Present address: Faculty of Veterinary Medicine, College of Agriculture, Can Tho University, Can Tho 900000, Vietnam.

^‡

Present address: Faculty of Animal Sciences, College of Agriculture, Can Tho University, Can Tho 900000, Vietnam.

Vaccines 2026, 14(4), 291; https://doi.org/10.3390/vaccines14040291

Submission received: 26 December 2025 / Revised: 13 March 2026 / Accepted: 23 March 2026 / Published: 24 March 2026

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

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Abstract

Background/Objectives: Biosecurity and stamping out are key control measures against H5 high-pathogenicity avian influenza (HPAI) outbreaks. Vaccination in poultry is an additional tool to reduce disease risk and facilitate timely containment. This study aimed to establish a candidate vaccine strain against H5 HPAI in Asia and validate its protective efficacy. Methods: Based on genetic and antigenic analyses, a representative HPAI virus, A/duck/Vietnam/HU16-DD3/2023 (H5N1), collected in northern Vietnam, was selected to generate a candidate vaccine strain, rgPR8/VN23HA∆KRRK-NA (rgPR8/VN23; H5N1), using reverse genetics, followed by formulation of an inactivated oil-adjuvanted vaccine. Vaccine efficacy was evaluated by measuring humoral antibody responses after intramuscular vaccination and by assessing mortality and virus recovery following intranasal challenge with a clade 2.3.4.4b virus, A/Ezo red fox/Hokkaido/1/2022 (H5N1). Results were compared with those obtained using an antigenically homologous vaccine to the challenge strain and a Japanese stockpiled vaccine. Results: All vaccinated juvenile chickens developed sufficient immunity to survive the challenge at 21 days post-vaccination. The rgPR8/VN23 (H5N1) and homologous vaccines markedly reduced virus recovery, suggesting near-sterile protection, whereas low-titer viruses were transiently detected in chickens vaccinated with the stockpiled vaccine. The rgPR8/VN23 (H5N1) vaccine conferred clinical protection in juvenile chickens as early as 8 days post-vaccination. A single dose of the rgPR8/VN23 (H5N1) vaccine provided incomplete protection in laying hens, whereas a double-volume regimen improved protective efficacy. Conclusions: The rgPR8/VN23 (H5N1) vaccine conferred strong immunity to juvenile chickens; however, a refined vaccination strategy may be required to achieve complete protection in laying hens.

Keywords: AIV; candidate vaccine strain; chickens; clade 2.3.4.4b; egg products; H5 HPAIV; inactivated vaccine; laying hens; virus contamination

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MDPI and ACS Style

Nguyen, B.L.; Isoda, N.; Hew, Y.L.; Huynh, L.T.; Le, K.T.; Shimazu, Y.; Kobayashi, D.; Nguyen, D.H.; Nguyen, T.D.; Chu, D.-H.; et al. Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza. Vaccines 2026, 14, 291. https://doi.org/10.3390/vaccines14040291

AMA Style

Nguyen BL, Isoda N, Hew YL, Huynh LT, Le KT, Shimazu Y, Kobayashi D, Nguyen DH, Nguyen TD, Chu D-H, et al. Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza. Vaccines. 2026; 14(4):291. https://doi.org/10.3390/vaccines14040291

Chicago/Turabian Style

Nguyen, Bao Linh, Norikazu Isoda, Yik Lim Hew, Loc Tan Huynh, Kien Trung Le, Yo Shimazu, Daiki Kobayashi, Dang Hoang Nguyen, Tho Dang Nguyen, Duc-Huy Chu, and et al. 2026. "Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza" Vaccines 14, no. 4: 291. https://doi.org/10.3390/vaccines14040291

APA Style

Nguyen, B. L., Isoda, N., Hew, Y. L., Huynh, L. T., Le, K. T., Shimazu, Y., Kobayashi, D., Nguyen, D. H., Nguyen, T. D., Chu, D.-H., Nguyen, D. T., Takeichi, K., Nanba, Y., Hiono, T., Sasaki, T., & Sakoda, Y. (2026). Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza. Vaccines, 14(4), 291. https://doi.org/10.3390/vaccines14040291

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Efficacy and Limitations of an Improved Vaccine Derived from an Updated Vaccine Strain Against H5 HighPathogenicity Avian Influenza

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