Li Rui, Chowdhury Mohammed Y E, Kim Jae-Hoon, Kim Tae-Hwan, Pathinayake Prabuddha, Koo Wan-Seo, Park Min-Eun, Yoon Ji-Eun, Roh Jong-Bok, Hong Seung-Pyo, Sung Moon-Hee, Lee Jong-Soo, Kim Chul-Joong
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea.
College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea; Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong 4202, Bangladesh.
Vet Microbiol. 2015 Sep 30;179(3-4):250-63. doi: 10.1016/j.vetmic.2015.07.020. Epub 2015 Jul 17.
The development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. In this study, we constructed and expressed conserved sM2 and HA2 influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei provided better protection of BALB/c mice against 10 times the 50% mouse lethal doses (MLD50) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic bird/Korea/W81/2005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with L. casei harboring sM2HA2 and also the protection was maintained up to seven months after administration. These results indicate that recombinant L. casei expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal adjuvant could be a potential mucosal vaccine candidate or tool to protect against divergent influenza viruses for human and animal.
开发一种能对现有和未知流感病毒提供广泛交叉保护的通用流感疫苗是一项严峻挑战。在本研究中，我们构建并表达了保守的流感病毒基质蛋白2（sM2）和血凝素2（HA2）抗原，并将霍乱毒素A1亚基（CTA1）展示在干酪乳杆菌表面（pgsA - CTA1sM2HA2/干酪乳杆菌）。对小鼠进行口服和鼻内给予重组干酪乳杆菌后，血清免疫球蛋白G（IgG）及其亚型（IgG1和IgG2a）以及黏膜IgA水平升高。黏膜给予pgsA - CTA1sM2HA2/干酪乳杆菌还可能显著提高sM2或HA2特异性细胞介导免疫的水平，因为观察到干扰素 - γ（IFN - γ）和白细胞介素 - 4（IL - 4）的释放均增加。与携带sM2HA2的干酪乳杆菌相比，重组pgsA - CTA1sM2HA2/干酪乳杆菌能更好地保护BALB/c小鼠抵御10倍50%小鼠致死剂量（MLD50）的同源A/EM/韩国/W149/06（H5N1）或A/水鸟/韩国/W81/2005（H5N2）以及异源A/波多黎各/8/34（H1N1）、A/鸡/韩国/116/2004（H9N2）或A/菲律宾/2/08（H3N2）病毒，并且在给药后长达七个月仍保持这种保护作用。这些结果表明，表达流感病毒高度保守的sM2、HA2以及作为黏膜佐剂的CTA1的重组干酪乳杆菌可能是一种潜在的黏膜疫苗候选物或工具，用于保护人类和动物抵御多种流感病毒。
