Protection of Chickens against H9N2 Avian Influenza Isolates with a Live Vector Vaccine Expressing Influenza Hemagglutinin Gene Derived from Y280 Avian Influenza Virus

Jun-Feng Zhang; Sang-Won Kim; Ke Shang; Jong-Yeol Park; Yu-Ri Choi; Hyung-Kwan Jang; Bai Wei; Min Kang; Se-Yeoun Cha

doi:10.3390/ani14060872

Protection of Chickens against H9N2 Avian Influenza Isolates with a Live Vector Vaccine Expressing Influenza Hemagglutinin Gene Derived from Y280 Avian Influenza Virus

Animals (Basel). 2024 Mar 12;14(6):872. doi: 10.3390/ani14060872.

Authors

Jun-Feng Zhang^{1

2}, Sang-Won Kim¹, Ke Shang^{1

3}, Jong-Yeol Park¹, Yu-Ri Choi¹, Hyung-Kwan Jang^{1

4}, Bai Wei¹, Min Kang^{1

4}, Se-Yeoun Cha¹

Affiliations

¹ Department of Avian Diseases, College of Veterinary Medicine and Center for Avian Disease, Jeonbuk National University, Iksan 54596, Republic of Korea.
² College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471003, China.
³ College of Animal Science and Technology, Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Henan University of Science and Technology, Luoyang 471000, China.
⁴ Bio Disease Control (BIOD) Co., Ltd., Iksan 54596, Republic of Korea.

Abstract

Since the outbreak of the H9N2/Y439 avian influenza virus in 1996, the Korean poultry industry has incurred severe economic losses. A novel possibly zoonotic H9N2 virus from the Y280-like lineage (H9N2/Y280) has been prevalent in Korea since June 2020, posing a threat to the poultry sector. Rapid mutation of influenza viruses urges the development of effective vaccines against newly generated strains. Thus, we engineered a recombinant virus rHVT/Y280 to combat H9N2/Y280. We integrated the hemagglutinin (HA) gene of the H9N2/Y280 strain into the US2 region of the herpesvirus of turkeys (HVT) Fc126 vaccine strain, utilizing CRISPR/Cas9 gene-editing technology. The successful construction of rHVT/Y280 was confirmed by polymerase chain reaction and sequencing, followed by efficacy evaluation. Four-day-old specific pathogen-free chickens received the rHVT/Y280 vaccine and were challenged with the H9N2/Y280 strain A21-MRA-003 at 3 weeks post-vaccination. In 5 days, there were no gross lesions among the vaccinated chickens. The rHVT/Y280 vaccine induced strong humoral immunity and markedly reduced virus shedding, achieving 100% inhibition of virus recovery in the cecal tonsil and significantly lowering tissue viral load. Thus, HVT vector vaccines expressing HA can be used for protecting poultry against H9N2/Y280. The induction of humoral immunity by live vaccines is vital in such cases. In summary, the recombinant virus rHVT/Y280 is a promising vaccine candidate for the protection of chickens against the H9N2/Y280.

Keywords: CRISPR/Cas9; H9N2; HA protein; NHEJ; Y280; turkey herpesvirus; vaccine efficacy.

Grants and funding

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through the Animal Disease Management Technology Advancement Support Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (122014-2&122059-2) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1C1B5033331).