Intracellular delivery of HA1 subunit antigen through attenuated Salmonella Gallinarum act as a bivalent vaccine against fowl typhoid and low pathogenic H5N3 virus
Intracellular delivery of HA1 subunit antigen through attenuated Salmonella Gallinarum act as a bivalent vaccine against fowl typhoid and low pathogenic H5N3 virus
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DOI：
10.1186/s13567-017-0446-1
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发表时间：
2017-08-07
影响因子：
4.4
通讯作者：
Lee, John Hwa
中科院分区：
文献类型：
--
作者：
Kamble, Nitin Machindra;Hyoung, Kim Je;Lee, John Hwa
针对流行的和新出现的低致病性禽流感（LPAI）病毒的不同毒株引入新型灭活油乳剂疫苗对于家禽而言不是经济上可行的选择。工程减毒鸡沙门氏菌（S.递送H5 LPAI抗原的鸡伤寒（Gallinarum）疫苗可用作针对禽伤寒和LPAI病毒的二价疫苗，同时仍提供经济可行性和血清监测能力。本研究通过基因工程的方法构建了抗LPAI病毒和鸡伤寒的JOL 1814双价疫苗候选株。利用鸡胚凝集素（HA）基因的重组质粒pMMP 65，将H5型LPAI病毒HA 1区蛋白通过pMMP 65组成型表达质粒进行表达。开发的JOL 1814的重要特征是将HA1抗原递送至腹膜巨噬细胞的胞质溶胶。用JOL 1814免疫鸡产生了显著水平的抗H5 HA1和S.免疫鸡的鸡球虫抗原。攻毒后，只有JOL 1814免疫的鸡在口咽和泄殖腔拭子中表现出明显更快的H5N3病毒清除，并且对野生型S.鸡同时，采用M2基因特异性实时荧光定量PCR技术对JOL 1814免疫鸡与H5N3 LPAI病毒感染鸡进行了鉴别。综上所述，目前的数据表明，JOL 1814可以是针对家禽中H5N3 LPAI和禽伤寒感染的有效的二价候选疫苗，同时仍然提供针对H5禽流感病毒的血清监测特性。
Introduction of novel inactivated oil-emulsion vaccines against different strains of prevailing and emerging low pathogenic avian influenza (LPAI) viruses is not an economically viable option for poultry. Engineering attenuated Salmonella Gallinarum (S. Gallinarum) vaccine delivering H5 LPAI antigens can be employed as a bivalent vaccine against fowl typhoid and LPAI viruses, while still offering economic viability and sero-surveillance capacity. In this study, we developed a JOL1814 bivalent vaccine candidate against LPAI virus infection and fowl typhoid by engineering the attenuated S. Gallinarum to deliver the globular head (HA1) domain of hemagglutinin protein from H5 LPAI virus through pMMP65 constitutive expression plasmid. The important feature of the developed JOL1814 was the delivery of the HA1 antigen to cytosol of peritoneal macrophages. Immunization of chickens with JOL1814 produced significant level of humoral, mucosal, cellular and IL-2, IL-4, IL-17 and IFN-gamma cytokine immune response against H5 HA1 and S. Gallinarum antigens in the immunized chickens. Post-challenge, only the JOL1814 immunized chicken showed significantly faster clearance of H5N3 virus in oropharyngeal and cloacal swabs, and 90% survival rate against lethal challenge with a wild type S. Gallinarum. Furthermore, the JOL1814 immunized were differentiated from the H5N3 LPAI virus infected chickens by matrix (M2) gene-specific real-time PCR. In conclusion, the data from the present showed that the JOL1814 can be an effective bivalent vaccine candidate against H5N3 LPAI and fowl typhoid infection in poultry while still offering sero-surveillance property against H5 avian influenza virus.