Mass vaccination with reassortment-impaired live H9N2 avian influenza vaccine.

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-08-03 DOI:10.1038/s41541-024-00923-y
Flavio Cargnin Faccin, C Joaquin Cáceres, L Claire Gay, Brittany Seibert, Nick van Bentem, Luis A Rodriguez, Ana Luiza Soares Fraiha, Matias Cardenas, Ginger Geiger, Lucia Ortiz, Silvia Carnaccini, Darrell R Kapczynski, Daniela S Rajao, Daniel R Perez
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Abstract

Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, concerns surrounding reversion, recombination, and unintended transmission have hindered the progress of MLV development for avian influenza in poultry. To address these concerns, we engineered reassortment-impaired, non-transmissible, safe, immunogenic, and protective MLVs through the rearrangement of internal gene segments and additional modifications to the surface gene segments HA and NA. The unique peptide marker aspartic acid-arginine-proline-alanine-valine-isoleucine-alanine-asparragine (DRPAVIAN) was incorporated into HA, while NA was modified to encode the chicken interleukin-18 (ckIL18) gene (MLV-H9N2-IL). In vitro, the MLV-H9N2 and MLV-H9N2-IL candidates demonstrated stability and virus titers comparable to the wild-type H9N2 strain. In chickens, the MLV-H9N2 and MLV-H9N2-IL candidates did not transmit via direct contact. Co-infection studies with wild-type virus confirmed that the altered HA and NA segments exhibited fitness disadvantages and did not reassort. Vaccinated chickens showed no clinical signs upon vaccination, all seroconverted, and the inclusion of ckIL18 in the MLV-H9N2-IL vaccine enhanced neutralizing antibody production. A significant decrease in viral loads post-challenge underscored the protective effect of the MLVs. The MLV-H9N2-IL vaccine, administered via drinking water, proved immunogenic in chickens in a dose-dependent manner, generating protective levels of neutralizing antibodies upon aggressive homologous virus challenge. In summary, this study lays the groundwork for safe MLVs against avian influenza suitable for mass vaccination efforts.

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使用重配受损的 H9N2 禽流感活疫苗进行大规模接种。
禽流感对家禽生产和全球食品安全构成严重威胁,促使许多国家制定了疫苗接种计划。改良活病毒 (MLV) 疫苗具有大规模应用的潜力,与现有方案相比具有明显优势。然而,围绕还原、重组和意外传播的担忧阻碍了针对家禽禽流感的 MLV 开发进程。为了解决这些问题,我们通过对内部基因片段进行重排,并对表面基因片段 HA 和 NA 进行额外修饰,设计出了重排受损、不可传播、安全、免疫原性和保护性的 MLV。在 HA 中加入了独特的肽标记天冬氨酸-精氨酸-脯氨酸-丙氨酸-缬氨酸-异亮氨酸-丙氨酸-天冬酰胺(DRPAVIAN),而 NA 则被修饰为编码鸡白细胞介素-18(ckIL18)基因(MLV-H9N2-IL)。在体外,MLV-H9N2 和 MLV-H9N2-IL 候选株表现出与野生型 H9N2 株相当的稳定性和病毒滴度。在鸡体内,MLV-H9N2 和 MLV-H9N2-IL 候选株不会通过直接接触传播。与野生型病毒的共感染研究证实,改变的 HA 和 NA 片段表现出适应性劣势,不会发生重配。接种疫苗的鸡在接种后没有出现任何临床症状,所有鸡都发生了血清转换,在 MLV-H9N2-IL 疫苗中加入 ckIL18 可提高中和抗体的产生。挑战后病毒载量的明显降低突出了 MLV 的保护作用。通过饮用水接种的 MLV-H9N2-IL 疫苗证明对鸡具有免疫原性,其免疫原性呈剂量依赖性,在受到同源病毒攻击时可产生保护性的中和抗体。总之,这项研究为开发适合大规模疫苗接种的安全禽流感 MLV 奠定了基础。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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