A Single Vaccination of Chimeric Bivalent Virus-Like Particle Vaccine Confers Protection Against H9N2 and H3N2 Avian Influenza in Commercial Broilers and Allows a Strategy of Differentiating Infected from Vaccinated Animals

Abstract

H9N2 and H3N2 are the two most important subtypes of low pathogenic avian influenza viruses (LPAIV) because of their ongoing threat to the global poultry industry and public health. Although commercially available inactivated H9N2 vaccines are widely used in the affected countries, endemic H9N2 avian influenza remains uncontrolled. In addition, there is no available avian H3N2 vaccine. Influenza virus-like particles (VLPs) are one of the most promising vaccine alternatives to traditional egg-based vaccines. In this study, to increase the immunogenic content of VLPs to reduce production costs, we developed chimeric bivalent VLPs (cbVLPs) co-displaying hemagglutinin (HA) and neuraminidase (NA) of H9N2 and H3N2 viruses with the Gag protein of bovine immunodeficiency virus (BIV) as the inner core using the Bac-to-Bac baculovirus expression system. The results showed that a single immunization of chickens with 40μg/0.3mL cbVLPs elicited an effective immune response and provided complete protection against H9N2 and H3N2 viruses. More importantly, cbVLPs with accompanying serological assays can successfully accomplish the strategy of differentiating infected animals from vaccinated animals (DIVA), making virus surveillance easier. Therefore, this cbVLP vaccine candidate would be a promising alternative to conventional vaccines, showing great potential for commercial development.

Towards broad-spectrum protection: the development and challenges of combined respiratory virus vaccines

“…The efficacy and adaptability of subunit vaccines are underscored by their successful application in diverse pathogens, including influenza (Vogel and Manicassamy, 2020), SARS-CoV-2 Heidary et al, 2022), and RSV (Papi et al, 2023). Utilizing various platforms, such as recombinant protein vaccines (Liu et al, 2021;Chavda et al, 2024), virus-like particles (VLPs) (Sun et al, 2022), and nanoparticles (Pilkington et al, 2021), these vaccines have demonstrated considerable promise, with (Cao et al, 2022) M2e: The Matrix 2 ectodomain of influenza virus; NTD: The N-Terminal domain of the SARS-CoV-2 spike protein; HA1 trimer: trimerized hemagglutinin 1 of influenza virus; RBD trimer: trimerized receptor binding site of SARS-CoV-2 spike protein; IAV: influenza A virus.…”

“…The efficacy and adaptability of subunit vaccines are underscored by their successful application in diverse pathogens, including influenza ( Vogel and Manicassamy, 2020 ), SARS-CoV-2 ( Dong Y. et al., 2020 ; Heidary et al., 2022 ), and RSV ( Papi et al., 2023 ). Utilizing various platforms, such as recombinant protein vaccines ( Liu et al., 2021 ; Chavda et al., 2024 ), virus-like particles (VLPs) ( Sun et al., 2022 ), and nanoparticles ( Pilkington et al., 2021 ), these vaccines have demonstrated considerable promise, with several vaccines receiving approval for human use or currently undergoing clinical trials. Moreover, subunit vaccines serve as a highly adaptable platform for the development of combined vaccines, capable of targeting multiple strains of viruses like human papillomavirus (HPV) and influenza ( Liu et al., 2021 ; Williamson, 2023 ).…”

Effects of DHAV-3 infection on innate immunity, antioxidant capacity, and lipid metabolism in ducks with different DHAV-3 susceptibilities

“…A previous study reported the occurrence of apoptosis in the liver during virus infection in 7-day ducklings, providing partial insight into the mechanism of liver injury ( Cao et al, 2020 ). It is crucial to elucidate the underlying pathogenic mechanism to mitigate economic losses associated with viral infectious diseases ( Chen et al, 2022 ; Sun et al, 2022 ; Wu et al, 2022 ).…”

The Chinese Hamster Ovary Cell-Based H9 HA Subunit Avian Influenza Vaccine Provides Complete Protection against the H9N2 Virus Challenge in Chickens

“…In addition to inactivated vaccines, current new research directions include virus-like particles [ 27 ], recombinant vector vaccines [ 28 ], live attenuated vaccines [ 29 ], nucleic acid vaccines [ 30 ], and subunit vaccines [ 31 ]. The development of different types of vaccines provides new options for the control of H9N2 AIV.…”