Aug 2026· Microorganisms· Vol 14, pp. 1719· 0 citations· 52 references
Medicine
TL;DR
The findings suggest that internal gene backbone compatibility may influence vaccine immunogenicity and warrant further validation to support a refined vaccine design strategy for H7N9 and potentially other avian influenza subtypes.
Abstract
H7N9 avian influenza virus (AIV) poses a persistent threat to poultry and public health. Despite widespread vaccination in China, rapid antigenic drift and reassortment necessitate frequent updates of vaccine strains. Phylogenetic analysis of isolates from Chinese provinces (from 2019 to 2023) showed that while surface genes diversified, the internal gene cassette remained conserved yet actively reassorted with other subtypes, suggesting internal gene compatibility may influence vaccine performance. We selected the H7N9 strain A/chicken/Northeast China/19854-6/2019 (E2), which harbors a polybasic Hemagglutinin (HA) cleavage site and predicted dual receptor-binding affinity. To enable safe vaccine development, we modified the HA cleavage site to generate a low-pathogenicity strain (E2-Δ). Using reverse genetics, we constructed three recombinant viruses: E2-Δ (retaining contemporary internal genes), CVI-E2, and CVII-E2 (containing internal genes from commercially used donor strains CVI and CVII, respectively). Inactivated vaccines were evaluated in specific-pathogen-free (SPF) chickens. E2-Δ induced HI antibody titers comparable to those of CVI-E2 and significantly higher than those of CVII-E2, and showed modestly higher cross-reactive HI titers against some recent H7N9 variants in exploratory analyses. All vaccines provided complete homologous protection with reduced viral shedding and no clinical signs in challenge trials. Our findings suggest that internal gene backbone compatibility may influence vaccine immunogenicity. While E2-Δ outperformed CVII-E2, it was comparable to CVI-E2, indicating that certain traditional backbones may still be suitable for H7N9 vaccine development. This approach warrants further validation to support a refined vaccine design strategy for H7N9 and potentially other avian influenza subtypes.
ABSTRACT The H9N2 avian influenza virus (AIV) has caused substantial economic losses to the global poultry industry and poses a zoonotic threat to humans. Vaccination constitutes a pivotal strategy for the prevention and control of H9N2 AIVs. However, the ongoing antigenic evolution of the viruses pose a persistent challenge to the protective efficacy of existing vaccines. Therefore, the development of a broadly protective H9N2 influenza vaccine capable of eliciting cross-reactive immune responses is crucial for mitigating both the disease burden and the risk of pandemics. Here, we developed a bivalent chimeric inactivated vaccine, designated cHANA, by combining two individually rescued chimeric inactivated viruses, cHANA1 and cHANA2. Each recombinant virus carries one set of Epigraph-designed HA and NA immunogens, and the two sets were computationally optimized from global H9N2 HA and NA sequence datasets to complement each other in epitope coverage across the H9N2 viral population. Compared to the WHO-recommended candidate vaccine virus (CVV), AL/39, cHANA elicited more potent cross-reactive antibody responses and T cell immunity in mice. Furthermore, it elicited effective cross-protection against lethal challenge with heterologous H9N2 virus and significantly reduced pulmonary viral loads of mice. By conferring broad protective immunity, this vaccine represents a promising universal vaccine candidate for controlling H9N2 outbreaks.
Mengchan Hao, Yiwei Guan, Meng Xu et al.· Emerging Microbes and Infect...· 0 citations
It is demonstrated that the attenuated strain AHFY‐F140 represents a promising vaccine candidate against both NADC30‐like and JXA1‐like PRRSV infections.
Hengjiao Zhang, Jiakai Zhao, Chengxin Zhang et al.· Transboundary and Emerging D...· 0 citations
Summary Background Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo. Methods In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated. Findings Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses. Interpretation An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic. Funding This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the 10.13039/100009619Japan Agency for Medical Research and Development.
Ryuta Uraki, Maki Kiso, K. Iwatsuki-Horimoto et al.· EBioMedicine· 0 citations
The H9N2 subtype of avian influenza A virus has been endemic in poultry populations across Asia and the Middle East, posing ongoing economic and public health concerns. Since their initial detection in Pakistan in the 1990s, H9N2 viruses have caused repeated outbreaks in commercial poultry, leading to substantial economic losses and raising concerns about zoonotic transmission. To characterize the recent genetic evolution and zoonotic potential of circulating strains, five H9N2 isolates were obtained from poultry in Pakistan between January and March 2023. Phylogenetic analysis of the haemagglutinin gene revealed that all five isolates belong to the G5.3.2, formerly known as B2, sub-lineage of the G1 Eurasian lineage, in accordance with the revised global classification system for H9 viruses. Comparative genomic analysis confirmed that all eight gene segments were closely related to previously reported Pakistani strains, with no evidence of recent reassortment, suggesting localized persistence and ongoing genetic drift. Notably, several mammalian-adaptive mutations were identified in internal gene segments of the isolates, suggesting a potential risk of cross-species transmission. In addition, all five isolates exhibited dual receptor-binding characteristics, recognizing both α2,3-linked (avian-type) and α2,6-linked (human-type) sialic acid glycans, with a stronger affinity for α2,6-linked glycans. These findings underscore the need for continuous surveillance and risk assessment of H9N2 viruses circulating in Pakistan.
Kai-Yun Tan, Nousheen Arshad, Salman L. Butt et al.· Avian Pathology· 0 citations
Due to the continuous evolution of Influenza A viruses (IAVs), novel strains with efficient human-to-human transmission may emerge and cause future pandemics. Among these, highly pathogenic avian influenza (HPAI) H5N1 remains a major concern because of its impact on wildlife, livestock, and human health. The widespread circulation of H5N1 clade 2.3.4.4b, detected in hundreds of bird species and numerous mammals worldwide, highlights important changes in viral ecology and transmission, increasing its zoonotic and pandemic potential. This review summarizes current evidence on cross-reactive and cross-protective immunity to H5N1 in humans, focusing primarily on humoral immune responses. We examine the presence of pre-existing H5N1-reactive antibodies in individuals without known exposure and discuss how previous seasonal influenza infection or vaccination may contribute to their development. Particular attention is given to antibodies targeting conserved regions of hemagglutinin (HA), especially the stalk domain, as well as neuraminidase (NA), which may provide heterosubtypic protection. We also evaluate the ability of seasonal influenza vaccines and infections to induce cross-reactive responses against H5N1 and their potential role in partial protection or immune priming. Finally, we review current and emerging H5N1 vaccination strategies, including adjuvanted and mRNA-based platforms, and identify priorities for surveillance, population immunity assessment, and the development of broadly protective influenza vaccines.
Iván Sanz-Muñoz, Carlos J. Ciria-Gil, Marta Hernández et al.· Journal of Infection· 0 citations
Highly pathogenic avian influenza viruses (HPAIs) continue to threaten both agriculture and human health. Recent H5N1 clades have caused zoonotic infections in humans with mortality rates approaching 50%. However, currently licensed H5 vaccines are based on ancestral strains and may provide suboptimal protection against circulating variants. Rapidly adaptable DNA vaccine platforms offer a promising approach for clade-specific protection.
Codon-optimized plasmid DNA vaccines expressing hemagglutinin (HA) from two recently circulating H5N1 clades (2.3.2.1c and 2.3.4.4b) were generated and delivered by either intramuscular electroporation (EP) or a lipid nanoparticle (LNP) formulation. Cellular and humoral responses were evaluated by multiparameter flow cytometry and ELISpot and by ELISA and pseudovirus neutralization, respectively. Protective efficacy was evaluated in lethal H5N1 murine challenge models.
EP delivery of clade 2.3.2.1c HA (pCamb) elicited strong humoral and cellular responses and achieved complete protection against homologous viral challenge, but only partial protection against heterologous 2.3.4.4b challenge. In contrast, vaccination with clade 2.3.4.4b HA (pMich) DNA supported robust immune responses and full protection against contemporary clade challenge. Co-immunization with both plasmids via EP induced broad binding and neutralizing antibodies and conferred complete protection from clade 2.3.4.4b challenge. Moreover, formulation of the pMich plasmid optimized LNPs generated durable, protective immunity following a single dose, effective at both acute and memory timepoints.
These studies demonstrate that antigenic clade-matching is likely critical for protection against H5N1 and suggest that currently stockpiled H5N1 vaccines may not protect against contemporary viruses. Further this data suggests that DNA vaccine platforms including EP or LNP formulations can provide a flexible approach for rapid adaptation to evolving influenza strains.
NIH NIAID CIVICs
Vaccines and Immunotherapy (VAC)
Ebony N. Gary, Nicholas J. Tursi, Casey E. Hojecki et al.· Journal of Immunology· 0 citations
