Vaccine optimization for highly pathogenic avian influenza: Assessment of antibody responses and protection for virus-like particle vaccines in chickens

Chia-Chi Ku; Cheng-Yu Lin; Chin-Rur Yang; Yu-Chih Yang; Po-Ling Chen; Yi-Te Lin; Pei-Ru Wang; Min-Shi Lee; Shu-Mei Liang; Pei-Wen Hsiao

doi:10.1016/j.jvacx.2024.100552

Vaccine optimization for highly pathogenic avian influenza: Assessment of antibody responses and protection for virus-like particle vaccines in chickens

Vaccine X. 2024 Sep 6:20:100552. doi: 10.1016/j.jvacx.2024.100552. eCollection 2024 Oct.

Authors

Affiliations

¹ Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei 10051, Taiwan.
² Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Rd., Section 2, Nankang, Taipei 11529, Taiwan.
³ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.

Abstract

Background: Recent outbreaks of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses in regions previously less affected since 2020 have raised global concerns. Implementing mass immunization or ring vaccination in poultry should be a countermeasure ready to contain disease outbreaks. This study focuses on developing a recombinant H5N2 vaccine based on virus-like particles (VLPs) against clade 2.3.4.4c, the predominant HPAI subclade in Taiwan since its emergence, leading to a large outbreak in 2015.

Methods: The study aimed to confirm the effectiveness of clade 2.3.4.4c H5N2 VLPs in protecting chickens and identify the best adjuvants for the VLP vaccine. We used Montanide 71VG-adjuvanted inactivated RG6 to establish the immunization protocol, followed by prime-boost H5N2-VLP immunizations. We compared adjuvants: 71VG, 71VG with VP3, and Alum with VP3. Serum samples were tested for antibodies against homologous vaccine antigens and cross-clade antigens by hemagglutination inhibition (HI) assays. Finally, we evaluated the protective efficacy by lethally challenging immunized chickens with H5 viruses from clade 1 or 2.3.4.4c.

Results: Poultry adjuvant 71VG significantly enhanced antibody responses in chickens with inactivated RG6 compared to unadjuvanted inactivated virus. While increasing antigen dosage enhanced 71VG adjuvanted RG6-induced antibody titers, the vaccine displayed minimal cross-reactivity against locally circulating HPAI H5N2. In contrast, H5N2-VLP containing the HA protein of clade 2.3.4.4c, adjuvanted with (FMDV) VP3 in 71VG, significantly promoted HI antibody responses. All H5N2-VLP immunized chickens survived lethal challenges with the local clade 2.3.4.4c H5 strain.

Conclusion: The study demonstrated the immunogenic potential of the VLP vaccine in chickens. Our findings offer insights for optimizing VLP vaccines, allowing the incorporation of the HA of currently circulating H5 viruses to effectively mitigate the impact of the rapidly evolving clade 2.3.4.4 H5 outbreaks.

Keywords: Chicken; H5N2 subtype; Highly pathogenic avian influenza (HAPI); Poultry vaccination; Virus-like particles.