Interpretative summary: An avian-origin internal backbone effectively increases the H5 subtype avian influenza vaccine candidate yield in both chicken embryonated eggs and MDCK cells.
by María José Valdez, University of Autonomous of Barcelona
Researchers from the College of Veterinary Medicine of the Yangzhou University in China conducted a study aimed at enhancing the yield and effectiveness of avian influenza (AI) vaccines. The study addresses the critical need for high-yield inactivated vaccine strains in preventing high pathogenic avian influenza (HPAI) virus, which poses a significant threat to the poultry industry and public health.
The main objective was to develop and evaluate a new high-yield vaccine for AI by using the clade 2.3.4.4d H5 subtype AIV CkG strain for surface proteins and the AIV Dk8 strain, which exhibits high replicative capacity in chicken embryos and MDCK cells, as the vaccine backbone. The study aimed to optimize the vaccine candidates, assess their biological characteristics, and evaluate their immunogenicity and protective efficacy.
To achieve this, recombinant viruses were constructed using the H5N6 CkG strain as the surface protein donor and the H5N6 Dk8 strain, which has high replicative ability, as the internal donor. The integration of the M gene from CkG into the internal genes of Dk8 (8GM) was selected as the high-yield vaccine backbone to improve the HA1/NP ratio in recombinant viruses. The replication kinetics of these viruses were assessed in chicken embryo fibroblast (CEF) and MDCK cells, with infectivity measured using standard TCID50 methods. In vivo, six-week-old SPF chickens (10 per group) were used to evaluate viral pathogenicity. Each virus was inoculated, and clinical signs were monitored for 10 days, during which intravenous pathogenicity indices (IVPI) were calculated. For protection studies, three-week-old SPF chickens (eight groups of 10 each) were immunized with vaccine candidates or phosphate buffered saline (PBS). Serum samples were collected on Days 7, 14, and 21 to measure hemagglutination inhibition (HI) and microneutralization (MNT) titers. After immunization, chickens were challenged with the H5N6 CkG strain and viral shedding was monitored.
This study identified the H5 subtype AIV Dk8 strain as an efficient replicator in both eggs and MDCK cells. Notably, substituting the M gene from the H5 subtype AIV CkG strain into the Dk8 backbone significantly increased viral titers in MDCK cells, demonstrating enhanced viral yields in both cell cultures and chicken embryonated eggs. Genetic analysis revealed that the M segment of the CkG strain contributed to the higher replication ability of 8GM-based vaccine candidates. Additionally, vaccine candidates with this optimized donor exhibited higher growth titers compared to Dk8 in both cell and egg cultures. The study confirmed that the M gene from the CkG strain enhances vaccine production by influencing gene expression. Chicken experiments showed that these vaccine candidates provided survival protection after H5 subtype AIV challenge. The birds had higher HI and MNT titers, which indicated strong immunogenicity and immune protection.
What does this mean for producers?
-
The avian-origin backbone provides an alternative to the traditional PR8 backbone, potentially reducing compatibility issues with H5 subtype HA and NA genes. This results of this study suggest it could be used to manufacture more effective vaccines against avian influenza.
-
Farmers and producers can expect better protection for their flocks due to the higher immunogenicity and protective efficacy of this vaccine candidate.
Yang, F., Zhao, X., Huo, C., Miao, X., Qin, T., Chen, S., Peng, D. and Liu, X., 2024. An avian-origin internal backbone effectively increases the H5 subtype avian influenza vaccine candidate yield in both chicken embryonated eggs and MDCK cells. Poul. Sci. 103:103988.
DOI. https://doi.org/10.1016/j.psj.2024.103988
#InterpretiveSummary #PoultryIndustry #Vaccination