Ito Takashi, Kumagai Takuji, Yamaji Yoshiaki, Sawada Akihito, Nakayama Tetsuo
Laboratory of Viral Infection II, Kitasato Institute for Life Sciences, Tokyo 108-8641, Japan.
Kumagai Pediatric Clinic, Sapporo 004-0051, Japan.
Vaccines (Basel). 2020 Mar 27;8(2):149. doi: 10.3390/vaccines8020149.
Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (10 TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (10 TCID50/g) or the group immunized with HA split vaccine (10 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats.
构建了表达甲型流感病毒/札幌/107/2013(H1N1pdm)血凝素(HA)蛋白的重组麻疹AIK-C疫苗(MVAIK/PdmHA)。用MVAIK/PdmHA免疫的棉鼠体内诱导产生了麻疹颗粒凝集(PA)抗体和流感血凝素抑制(HI)抗体。用两剂HA裂解疫苗免疫的棉鼠用作阳性对照,在首剂接种3周后检测到更高的HI抗体。在用A/加利福尼亚/07/2009(H1N1pdm)攻击后,在空载体(MVAIK)免疫的棉鼠或对照组的肺匀浆中检测到的病毒载量(10 TCID50/g)高于用MVAIK/Pdm HA免疫(10 TCID50/g)或用HA裂解疫苗免疫的组(10 TCID50/g)。组织病理学检查显示,在攻击后,未免疫大鼠和用空载体免疫的大鼠的肺组织中检测到肺泡结构破坏、支气管上皮细胞肿胀、肺泡壁增厚以及炎性细胞和HA抗原浸润,但在用HA裂解疫苗或MVAIK/PdmHA疫苗免疫的大鼠中未检测到。在MVAIK/PdmHA组的肺匀浆中发现IFN-α、IL-1β和TNF-α mRNA水平较低,而IFN-γ mRNA水平较高。在用紫外线灭活的A/加利福尼亚/07/2009(H1N1pdm)刺激的MVAIK/PdmHA组的脾细胞培养物中检测到较高水平的IFN-γ mRNA。总之,表达流感HA蛋白的重组MVAIK疫苗在棉鼠中诱导了保护性免疫反应。