Oral immunization with an attenuated Salmonella Gallinarum encoding the H9N2 haemagglutinin and M2 ectodomain induces protective immune responses against H9N2 infection in chickens
Oral immunization with an attenuated Salmonella Gallinarum encoding the H9N2 haemagglutinin and M2 ectodomain induces protective immune responses against H9N2 infection in chickens
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DOI：
10.1080/03079457.2020.1775782
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发表时间：
2020-06-17
期刊：
影响因子：
2.8
通讯作者：
Lee, John Hwa
中科院分区：
文献类型：
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作者：
Hajam, Irshad Ahmed;Kirthika, Perumalraja;Lee, John Hwa
H9N2是一种低致病性禽流感病毒，在世界范围内给养禽业造成了巨大的经济损失。在此，我们描述了鸡沙门氏菌(SG)减毒株的构建，用于表达和传递H9N2血凝素(HA)1(SG-HA1)、HA2(SG-HA2)和/或保守的基质蛋白2胞外结构域(SG-M2e)。我们在鸡模型中证明了表达HA1、HA2和M2e抗原的重组SG株具有免疫原性和安全性。8只鸡分别口服SG、SG-HA1、SG-HA2、SG-M2e或SG-HA1、SG-HA2和SG-M2e混合疫苗一次，或肌肉注射一次油佐剂灭活疫苗。我们的结果表明，单独或混合接种编码流感抗原的SG突变体，与单独接种SG的鸡相比，显著(P<；0.05)诱导了更高的抗原特异性体液和细胞免疫应答。与基于SG的H9N2疫苗株相比，常规H9N2疫苗显著(P<；0.05)诱导更多的HA1和HA2抗体反应，但显著(P<；0.05)不那么强劲的M2e特异性反应。在接种后第28天与强毒H9N2病毒进行攻击时，接种基于SG的H9N2疫苗或传统H9N2疫苗的鸡表现出相似的肺部炎症和病毒载量，尽管两者都显著低于单独接种SG的组(P<；0.05)。综上所述，我们的结果表明，基于SG的疫苗能刺激针对强毒H9N2的有效免疫应答。需要进一步研究以充分发展这一方法，将其作为影响家禽的低致病性禽流感病毒的预防战略。
H9N2, a low pathogenic avian influenza virus, causes significant economic losses in the poultry industry worldwide. Herein, we describe the construction of an attenuatedSalmonellaGallinarum (SG) strain for expression and delivery of H9N2 haemagglutinin (HA) 1 (SG-HA1), HA2 (SG-HA2) and/or the conserved matrix protein 2 ectodomain (SG-M2e). We demonstrated that recombinant SG strains expressing HA1, HA2 and M2e antigens were immunogenic and safe in a chicken model. Chickens (n = 8) were vaccinated once orally with SG alone, SG-HA1, SG-HA2, SG-M2e, or mixture of SG-HA1, SG-HA2 and SG-M2e, or vaccinated once intramuscularly with an oil-adjuvant inactivated H9N2 vaccine. Our results demonstrated that vaccination with SG mutants encoding influenza antigens, administered individually or as a mixture, elicited significantly (P < 0.05) greater antigen-specific humoral and cell-mediated immune responses in chickens compared with those vaccinated with SG alone. A conventional H9N2 vaccine induced significantly (P < 0.05) greater HA1 and HA2 antibody responses than SG-based H9N2 vaccine strains, but significantly (P < 0.05) less robust M2e-specific responses. Upon challenge with the virulent H9N2 virus on day 28 post-vaccination, chickens vaccinated with either the SG-based H9N2 or conventional H9N2 vaccines exhibited comparable lung inflammation and viral loads, although both were significantly lower (P < 0.05) than in the group vaccinated with SG alone. In conclusion, our results showed that SG-based vaccination stimulated efficient immune responses against virulent H9N2. Further studies are needed to fully develop this approach as a preventive strategy for low pathogenic avian influenza viruses affecting poultry.