A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine.
A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine.
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DOI：
10.1038/s41541-022-00498-6
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发表时间：
2022-06-29
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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作者：
针对目前普遍使用的单分子域HA疫苗免疫效果差的缺点，通过基因工程技术将H3茎域与保守的M2 e表位结合，构建了一种新型的M2 e-H3茎域HA嵌合疫苗（M2 e-H3 stalk）。从大肠杆菌中表达和纯化的M2 e-H3茎蛋白是热稳定的，显示天然样抗原表位识别的不同HA亚型蛋白的抗血清和A型流感病毒感染。佐剂M2 e-H3茎部疫苗接种诱导小鼠中识别病毒颗粒和感染细胞表面上的病毒抗原的M2 e和茎部特异性IgG抗体、CD 4+和CD 8 + T细胞应答以及抗体依赖性细胞毒性细胞替代活性。发现M2 e-H3茎部在成年和老年小鼠中以相似的水平提供针对异源和异亚型交叉组亚型病毒（H1N1、H5 N1、H9 N2、H3 N2、H7N9）的保护。这些结果提供了证据表明，M2 e-H3茎嵌合蛋白可以被开发为用于年轻和老年人群的通用甲型流感病毒疫苗候选物。
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.
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影响因子：
5.5
作者：
Kim, Min-Chul;Lee, Yu-Na;Hwang, Hye Suk;Lee, Young-Tae;Ko, Eun-Ju;Jung, Yu-Jin;Cho, Min Kyoung;Kim, Yu-Jin;Lee, Jong Seok;Ha, Suk-Hoon;Kang, Sang-Moo
通讯作者：
Kang, Sang-Moo
DOI：
10.15585/mmwr.mm6722a4
发表时间：
2018-06-08
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Garten R;Blanton L;Elal AIA;Alabi N;Barnes J;Biggerstaff M;Brammer L;Budd AP;Burns E;Cummings CN;Davis T;Garg S;Gubareva L;Jang Y;Kniss K;Kramer N;Lindstrom S;Mustaquim D;O'Halloran A;Sessions W;Taylor C;Xu X;Dugan VG;Fry AM;Wentworth DE;Katz J;Jernigan D
通讯作者：
Jernigan D
影响因子：
12.4
作者：
Kim, Min-Chul;Song, Jae-Min;Kang, Sang-Moo
通讯作者：
Kang, Sang-Moo
DOI：
10.1073/pnas.1007465107
发表时间：
2010-08-03
影响因子：
11.1
作者：
Bommakanti, Gayathri;Citron, Michael P.;Varadarajan, Raghavan
通讯作者：
Varadarajan, Raghavan
影响因子：
5.4
作者：
Krammer, Florian;Pica, Natalie;Palese, Peter
通讯作者：
Palese, Peter