Comparative protective efficacy of a newly generated live recombinant thermostable highly attenuated vaccine rK148/GVII-F using a single regimen against lethal NDV GVII.1.1

ABSTRACT

The ongoing global spread of Newcastle disease underscores the crucial need for continued research on the efficacy of current vaccines against various circulating strains of Newcastle disease virus (NDV). The fusion gene of a representative Egyptian genotype VII.1.1 strain was used to substitute its corresponding gene in the K148/08 vaccinal strain after site directly mutating its cleavage site from 112RRQKRF117 to 112GKQGRL117. Fusion gene exchange between GVII and GI did not affect the thermostability of GI K148/08. Attenuation of the rescued virus was confirmed by mean death time 144 h with an intracerebral pathogenicity index of 0.00. Survival analysis after the challenge experiment confirmed that 10⁷ EID₅₀ was the protective dose of rK148/GVII-F. The haemagglutination inhibition level of antibodies required for full clinical protection was > 3.3 log₂ for rK148/GVII-F and > 4.1 log₂ for both K148/08 and LaSota. Oropharyngeal viral shedding was reduced on the 5th and 7th days post-challenge in the rK148/GVII-F vaccinated group. Replication and tropism investigations confirmed the respirotropic nature of LaSota, enterotropic nature of K148/08, and further attenuation of rK148/GVII-F. Altogether, rK148/GVII-F is a thermostable, safe, effective, and genetically stable vaccine candidate that could be adequate for use in countries that encounter GVII.1.1 and in those with tropical climate, such as most Middle Eastern countries.

RESEARCH HIGHLIGHTS

• A thermostable, safe, and effective NDV GVII recombinant vaccine was generated.

• Fusion gene replacement with GVII did not affect GI K148/08 virus thermostability.

• Strain rK148/GVII-F provided adequate protection against a lethal NDV challenge.

• Oropharyngeal shedding was significantly reduced on post-challenge days 5 and 7.

KEYWORDS:

• Newcastle disease virus
• genotype VII
• thermostability
• recombinant vaccine
• protective efficacy
• viral shedding

Acknowledgements

We would like to extend our sincere thanks to Professor Mustafa al-Bakri Sayf al-Din, Jinyong Noh, Yu-Jin Kim, Tae-Hyun Kim, Jun-Beom Kim, Kyu-jik Kim, Ha-na Youn, Jei-hyun Jeong, Sunhak Lee, Andrew Y. Cho and all KHAV team members, who generously shared their time, experiences, and insights with us.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This study is supported by the Bio and Medical Technology Development Program of the National Research Foundation, funded by the government of South Korea [grant number NRF-2018M3A9H4056535].