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用H5N1重组候选疫苗进行免疫接种可使鸡对越南高致病性禽流感病毒株产生高度保护。

Immunization with the H5N1 Recombinant Vaccine Candidate Induces High Protection in Chickens against Vietnamese Highly Pathogenic Avian Influenza Virus Strains.

作者信息

Hoang Hang Thi Thu, Nguyen Chi Hung, Nguyen Ngan Thi Thuy, Pham An Dang, Nguyen Hang Thi Thu, Le Thanh Hoa, Tran Hanh Xuan, Chu Ha Hoang, Nguyen Nam Trung

机构信息

Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), Hanoi 100000, Vietnam.

Graduate University of Science and Technology (GUST), VAST, Hanoi 100000, Vietnam.

出版信息

Vaccines (Basel). 2020 Apr 2;8(2):159. doi: 10.3390/vaccines8020159.

DOI:10.3390/vaccines8020159
PMID:32252383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7348806/
Abstract

Vietnam is one of the countries most affected worldwide by the highly pathogenic avian influenza (HPAI) virus, which caused enormous economic loss and posed threats to public health. Over nearly two decades, with the antigenic changes in the diversified H5Ny viruses, the limited protective efficacy of the available vaccines was encountered. Therefore, it is necessary to approach a technology platform for the country to accelerate vaccine production that enables quick response to new influenza subtypes. This study utilized a powerful reverse genetics technique to successfully generate a recombinant H5N1 vaccine strain (designated as IBT-RG02) containing two surface proteins (haemagglutinin (HA) and neuraminidase (NA)) from the HPAI H5N1 (A/duck/Vietnam/HT2/2014(H5N1)) of the dominant clade 2.3.2.1c in Vietnam during 2012-2014. Importantly, the IBT-RG02 vaccine candidate has elicited high antibody titres in chickens (geometric mean titre (GMT) of 6.42 and 6.92, log on day 14 and day 28 p.i., respectively). To test the efficacy, immunized chickens were challenged with the circulating virulent strains. As results, there was a high protection rate of 91.6% chickens against the virulent A/DK/VN/Bacninh/NCVD-17A384/2017 of the same clade and a cross-protection of 83.3% against A/duck/TG/NAVET(3)/2013 virus of clade 1.1. Our promising results showed that we can independently master the reverse genetics technology for generation of highly immunogenic vaccine candidates, and henceforth, it is a timely manner to reformulate avian influenza virus vaccines against variable H5 clade HPAI viruses in Vietnam.

摘要

越南是全球受高致病性禽流感(HPAI)病毒影响最严重的国家之一,该病毒造成了巨大的经济损失并对公众健康构成威胁。在近二十年里,随着多种H5Nx病毒的抗原性变化,现有疫苗的保护效果有限。因此,越南有必要采用一个技术平台来加速疫苗生产,以便能够对新的流感亚型做出快速反应。本研究利用强大的反向遗传学技术成功构建了一种重组H5N1疫苗株(命名为IBT-RG02),其包含来自2012 - 2014年越南优势进化枝2.3.2.1c的高致病性H5N1(A/duck/Vietnam/HT2/2014(H5N1))的两种表面蛋白(血凝素(HA)和神经氨酸酶(NA))。重要的是,候选疫苗IBT-RG02在鸡体内诱导出了高抗体滴度(分别在攻毒后第14天和第28天的几何平均滴度(GMT)为6.42和6.92,对数)。为测试其效力,对免疫的鸡用流行的强毒株进行攻毒。结果显示,针对同一进化枝的强毒株A/DK/VN/Bacninh/NCVD - 17A384/2017,鸡的保护率高达91.6%,针对进化枝1.1的A/duck/TG/NAVET(3)/2013病毒的交叉保护率为83.3%。我们的这些有前景的结果表明,我们能够自主掌握用于构建高免疫原性候选疫苗的反向遗传学技术,从今往后,及时重新制定针对越南可变H5进化枝高致病性禽流感病毒的禽流感病毒疫苗是很有必要的。