Safety, immunogenicity and efficacy of poxvirus-based vector vaccines expressing the haemagglutinin gene of a highly pathogenic H5N1 avian influenza virus in pigs
Safety, immunogenicity and efficacy of poxvirus-based vector vaccines expressing the haemagglutinin gene of a highly pathogenic H5N1 avian influenza virus in pigs
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DOI：
10.1016/j.vaccine.2009.02.006
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发表时间：
2009-04-06
期刊：
影响因子：
5.5
通讯作者：
Van Reeth, Kristien
中科院分区：
文献类型：
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作者：
Kyriakis, Constantinos S.;De Vleeschauwer, Annebel;Van Reeth, Kristien
本研究探讨了表达高致病性（HP）H5 N1禽流感病毒（AIV）（A/chicken/Indonesia/7/03）血凝素的不同痘载体疫苗在猪中的安全性、免疫原性和有效性。猪用鸡痘（TROVAC（R））、金丝雀痘（ALVAC（R））或牛痘（NYVAC）载体疫苗与水包油佐剂组合、用无佐剂NYVAC接种两次，间隔4周，或不接种。第二次接种后6周，所有猪均气管内用低致病性（LP）H5 N2 AIV A/chicken/Belgium/150/99攻毒。对血清进行血凝抑制（HI）试验，以检测疫苗血凝素来源的H5 N1 AIV、攻毒病毒和人A/Vietnam/1194/04 HPAIV。在攻击后，在攻击后24或72小时，比较猪的气管和4个肺叶中的H5 N2病毒复制。所有动物均对疫苗接种耐受良好。抗体滴度在第二次接种后2周达到峰值，并且针对疫苗病毒的抗体滴度比针对异源H5病毒的抗体滴度高2至4倍。含NYVAC和ALVAC佐剂的疫苗始终诱导比不含佐剂的TROVAC或NYVAC更高的抗体滴度。攻毒后，从所有未接种疫苗的猪中分离出H5 N2攻毒病毒，而21头接种疫苗的猪中有19头表现出完全的病毒学保护。痘病毒载体疫苗是安全的，免疫原性和有效的攻击与异源H5禽流感病毒，提供了一种替代经典的灭活疫苗。它们是否能抵御猪适应性H5病毒，还有待观察，这种病毒的复制能力可能比我们的挑战病毒强100-1000倍。(C)2009爱思唯尔有限公司保留所有权利。
This study investigates the safety, immunogenicity and efficacy of different pox-vector vaccines expressing the haemagglutinin of a highly pathogenic (HP) H5N1 avian influenza virus (AIV) (A/chicken/Indonesia/7/03) in pigs. Pigs were vaccinated twice, with a 4-week interval, with a fowlpox (TROVAC (R)), a canarypox (ALVAC (R)), or a vaccinia (NYVAC) vector vaccine combined with an oil-in-water adjuvant, with the unadjuvanted NYVAC, or left unvaccinated. Six weeks after the second vaccination, all pigs were challenged intra-tracheally with low pathogenic (LP) H5N2 AIV A/chicken/Belgium/150/99. Sera were examined in haemagglutination inhibition (HI) tests against the H5N1 AIV from which the vaccine haemagglutinin derived, the challenge virus and the human A/Vietnam/1194/04 HPAIV. After challenge pigs were compared for H5N2 virus replication in the trachea and 4 lung lobes at 24 or 72 h post-challenge. Vaccination was well tolerated by all animals. Antibody titres peaked 2 weeks after the second vaccination and were 2- to 4-fold higher against the vaccine virus than heterologous H5 viruses. The NYVAC and ALVAC adjuvanted vaccines consistently induced higher antibody titres than TROVAC or NYVAC without adjuvant. Following challenge, the H5N2 challenge virus was isolated from all unvaccinated pigs, while 19 out of 21 vaccinates showed complete virological protection. Pox-vector vaccines were safe, immunogenic and efficacious against challenge with a heterologous H5 AIV, offering an alternative to classical inactivated vaccines. It remains to be seen whether they would protect against a swine-adapted H5 virus, which may replicate 100-1000 times better than our challenge virus. (C) 2009 Elsevier Ltd. All rights reserved.