Hepatitis E vaccine recombinant(Xiamen Innovax Biotech Co. Ltd.)

Avian hepatitis E virus (aHEV), a member of the Hepeviridae family, poses substantial threats to poultry health and productivity, particularly through its detrimental impact on egg production in laying hens. This review elucidates the multifaceted mechanisms underlying aHEV-induced egg production decline in laying hens, focusing on direct viral-host interactions, immune dysregulation, and neuroendocrine disruption. aHEV exhibits strong tropism for reproductive organs, with active replication in ovarian tissues causing follicular apoptosis, structural damage, and hormonal imbalance. Viral proteins (ORF1-ORF3) drive pathogenesis through immune evasion, oxidative stress induction, and disruption of calcium metabolism. Notably, ORF2-mediated host receptor binding and ORF3-mediated viral egress synergistically impair ovarian function, while genotype-specific variations (e.g., gt3/gt5) influence tissue specificity and pathogenicity. Systemic inflammation and hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation further exacerbate reproductive dysfunction by altering gonadotropin signaling and estrogen synthesis. Despite advances in diagnostics (e.g., ORF2-based antigen assays) and limited vaccine development (e.g., China's Hecolin®), cross-protection against diverse aHEV genotypes remains inadequate. Emerging strains with enhanced virulence (e.g., SDXT20) and recombination potential highlight the urgent need for genotype-spanning interventions. We propose that antioxidant therapies, receptor-blocking strategies, and multi-epitope vaccines targeting conserved ORF2/ORF3 regions could mitigate aHEV's economic impact. Furthermore, unresolved questions regarding viral latency, transovarial transmission, and zoonotic risks necessitate integrated approaches combining organoid models, single-cell omics, and One Health surveillance to address this evolving challenge.

A safe and highly efficacious Escherichia coli-produced HPV-16/18 bivalent vaccine (Cecolin®) offers a cost-effective cervical cancer prevention measure. Here, we report data on the long-term efficacy and immunopersistence up to 10 years post-vaccination.

In the Phase III clinical trial (NCT01735006), 7372 women were enrolled and randomly assigned to receive the HPV or control vaccine (hepatitis E vaccine). Women from 2 sites (Xinmi City and Fengning County; N = 1986) were invited to participate in the extension study. Cervical samples were collected for ThinPrep Pap tests and HPV DNA testing. Serum samples from participants in the immune persistent subcohort (N = 300) were collected for neutralising antibody testing. The co-primary outcomes were high-grade cervical, vulvar or vaginal lesions and persistent infection (over 6 months) associated with HPV 16/18 in the per-protocol population.

A total of 1648 women participated in the extension study (806 from the vaccine group and 842 from the control group). Over a median 10.2-year follow-up, vaccine efficacy was 87.5% (95% CI 6.4-99.7) against high-grade cervical, vulvar or vaginal lesions (1 case in the vaccine group and 8 cases in the control group, P = 0.0391), and 97.0% (95% CI 78.9-100.0) against persistent infection (over 6 months, 1 case in the vaccine group and 32 cases in the control group, P < 0.0001) in the per-protocol population. The GMCs of neutralising antibodies peaked by month 7, declined through month 42, with HPV-16 plateauing and HPV-18 continuing to decline thereafter. At 114 months, 98.9% (93/94) of baseline seronegative participants remained seropositive for HPV-16 with the GMC of 61.84 IU/mL and 97.0% (98/101) remained seropositive for HPV-18 with the GMC of 18.73 IU/mL.

The E. coli-produced HPV 16/18 bivalent vaccine elicits sustained antibody responses and confers durable protection against HPV 16/18 associated high-grade cervical, vulvar or vaginal lesions and persistent infections for a minimum of 10 years post-vaccination.

National Key Research and Development Program of China (2023YFC2307602), National Natural Science Foundation of China (823B2086, 82273640), Beijing Natural Science Foundation (L244091), and Fundamental Research Funds for the Central Universities (20720220005).