Subbiah Jeeva, Oh Judy, Kim Ki-Hye, Shin Chong-Hyun, Park Bo Ryoung, Bhatnagar Noopur, Seong Baik-Lin, Wang Bao-Zhong, Kang Sang-Moo
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.
Department of Microbiology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
NPJ Vaccines. 2022 Jun 29;7(1):68. doi: 10.1038/s41541-022-00498-6.
We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expressed and purified from Escherichia coli was thermostable, displaying native-like antigenic epitopes recognized by antisera of different HA subtype proteins and influenza A virus infections. Adjuvanted M2e-H3 stalk vaccination induced M2e and stalk-specific IgG antibodies recognizing viral antigens on virus particles and on the infected cell surface, CD4 and CD8 T-cell responses, and antibody-dependent cytotoxic cell surrogate activity in mice. M2e-H3 stalk was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, H7N9) at similar levels in adult and aged mice. These results provide evidence that M2e-H3 stalk chimeric proteins can be developed as a universal influenza A virus vaccine candidate for young and aged populations.
我们通过对修饰的H3茎域进行基因工程改造,并将其与保守的M2e表位偶联,开发了一种新型嵌合M2e和H3血凝素(HA)茎蛋白疫苗(M2e-H3茎),以克服基于单体结构域的通用疫苗效力低下的缺点。从大肠杆菌中表达并纯化的M2e-H3茎蛋白具有热稳定性,展现出可被不同HA亚型蛋白抗血清和甲型流感病毒感染识别的类似天然的抗原表位。佐剂化的M2e-H3茎疫苗接种可诱导产生识别病毒颗粒和感染细胞表面病毒抗原的M2e和茎特异性IgG抗体、CD4和CD8 T细胞应答,以及小鼠体内抗体依赖性细胞毒性细胞替代活性。结果发现,M2e-H3茎在成年和老年小鼠中对异源和异亚型跨组亚型病毒(H1N1、H5N1、H9N2、H3N2、H7N9)具有相似水平的保护作用。这些结果证明,M2e-H3茎嵌合蛋白可开发成为针对年轻和老年人群的通用甲型流感病毒候选疫苗。