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电离辐射法灭活的H9N2禽流感疫苗经肠外或黏膜途径接种后的保护效力

Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes.

作者信息

Bortolami Alessio, Mazzetto Eva, Kangethe Richard Thiga, Wijewardana Viskam, Barbato Mario, Porfiri Luca, Maniero Silvia, Mazzacan Elisa, Budai Jane, Marciano Sabrina, Panzarin Valentina, Terregino Calogero, Bonfante Francesco, Cattoli Giovanni

机构信息

Department of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.

Animal Production and Health Laboratory, Department of Nuclear Sciences and Applications, Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency (IAEA), Vienna, Austria.

出版信息

Front Vet Sci. 2022 Jul 11;9:916108. doi: 10.3389/fvets.2022.916108. eCollection 2022.

Abstract

H9N2 viruses have become, over the last 20 years, one of the most diffused poultry pathogens and have reached a level of endemicity in several countries. Attempts to control the spread and reduce the circulation of H9N2 have relied mainly on vaccination in endemic countries. However, the high level of adaptation to poultry, testified by low minimum infectious doses, replication to high titers, and high transmissibility, has severely hampered the results of vaccination campaigns. Commercially available vaccines have demonstrated high efficacy in protecting against clinical disease, but variable results have also been observed in reducing the level of replication and viral shedding in domestic poultry species. Antigenic drift and increased chances of zoonotic infections are the results of incomplete protection offered by the currently available vaccines, of which the vast majority are based on formalin-inactivated whole virus antigens. In our work, we evaluated experimental vaccines based on an H9N2 virus, inactivated by irradiation treatment, in reducing viral shedding upon different challenge doses and compared their efficacy with formalin-inactivated vaccines. Moreover, we evaluated mucosal delivery of inactivated antigens as an alternative route to subcutaneous and intramuscular vaccination. The results showed complete protection and prevention of replication in subcutaneously vaccinated Specific Pathogen Free White Leghorn chickens at low-to-intermediate challenge doses but a limited reduction of shedding at a high challenge dose. Mucosally vaccinated chickens showed a more variable response to experimental infection at all tested challenge doses and the main effect of vaccination attained the reduction of infected birds in the early phase of infection. Concerning mucosal vaccination, the irradiated vaccine was the only one affording complete protection from infection at the lowest challenge dose. Vaccine formulations based on H9N2 inactivated by irradiation demonstrated a potential for better performances than vaccines based on the formalin-inactivated antigen in terms of reduction of shedding and prevention of infection.

摘要

在过去20年里,H9N2病毒已成为传播最为广泛的家禽病原体之一,并在多个国家达到地方流行程度。在地方流行国家,控制H9N2传播和减少其循环的努力主要依赖于疫苗接种。然而,H9N2对家禽的高度适应性,表现为最低感染剂量低、能复制到高滴度以及高传播性,严重阻碍了疫苗接种运动的效果。市售疫苗在预防临床疾病方面已显示出高效性,但在家禽物种中减少病毒复制水平和病毒排泄方面也观察到了不同的结果。抗原漂移和人畜共患感染机会增加是目前可用疫苗提供的不完全保护的结果,其中绝大多数基于福尔马林灭活的全病毒抗原。在我们的研究中,我们评估了基于经辐照处理灭活的H9N2病毒的实验性疫苗在不同攻毒剂量下减少病毒排泄的效果,并将其效力与福尔马林灭活疫苗进行了比较。此外,我们评估了灭活抗原的黏膜递送作为皮下和肌肉注射疫苗的替代途径。结果显示,在低至中等攻毒剂量下,皮下接种特定病原体无白来航鸡可获得完全保护并防止病毒复制,但在高攻毒剂量下病毒排泄减少有限。在所有测试攻毒剂量下,黏膜接种鸡对实验性感染的反应更具变异性,接种疫苗的主要效果是在感染早期减少感染禽类数量。关于黏膜接种,辐照疫苗是唯一一种在最低攻毒剂量下提供完全感染保护的疫苗。基于辐照灭活的H9N2疫苗制剂在减少病毒排泄和预防感染方面显示出比基于福尔马林灭活抗原的疫苗具有更好性能的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4c1/9309530/4d979b56f47a/fvets-09-916108-g0001.jpg

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