Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines.
Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines.
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DOI：
10.1371/journal.pone.0008754
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发表时间：
2010-01-18
期刊：
影响因子：
3.7
通讯作者：
August JT
中科院分区：
文献类型：
--
作者：
Tan PT;Heiny AT;Miotto O;Salmon J;Marques ET;Lemonnier F;August JT
流感病毒的免疫相关进化是极其复杂的，并且由于流行的流感毒株之间的高度抗原漂移，针对流感的当前疫苗必须针对每个流感季节重新配制。疫苗生产的延迟是应对大流行局势（如目前的H1N1毒株）的一个严重问题。免疫逃逸通常归因于病毒血凝素和神经氨酸酶蛋白的抗体识别减少，其突变率远大于内部非结构蛋白。作为一种可能的替代方案，已经研究了针对内部流感蛋白的T细胞表位结构域的疫苗，其对抗原变异不太敏感。表达HLA I类A*0201、A*2402和B*0702以及II类DRB 1 *1501、DRB 1 *0301和DRB 1 *0401的HLA转基因小鼠品系用196种流感H1 N1肽免疫，所述流感H1 N1肽含有人H1 N1、H3 N2、H1 N2、H5 N1和禽流感A毒株的高度保守蛋白质组序列的残基。通过IFN-γ ELISpot测定鉴定了54种引起63种HLA限制性肽特异性T细胞表位应答的肽。将这54种肽与2007-2009年人类H1N1序列进行比较，以在新的候选H1N1疫苗的设计中选择序列，该疫苗特异性靶向高度保守的HLA限制性T细胞表位。基于过去30年的序列保守性、高功能亲合力、与人肽的非同一性、成簇定位和与多个HLA等位基因的混杂性，选择PB 1、PB 2和M1中的十七（17）个T细胞表位作为疫苗靶标。这些候选疫苗抗原序列可适用于任何禽或人甲型流感病毒。
The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54) peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-γ ELISpot assay. The 54 peptides were compared to the 2007–2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes. Seventeen (17) T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus.
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DOI：
10.4161/hv.3.5.4175
发表时间：
2007-09-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Jimenez, Gretchen S.;Planchon, Rodrick;Smith, Larry R.
通讯作者：
Smith, Larry R.
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
5.4
作者：
Frahm, Nicole;Yusim, Karina;Brander, Christian
通讯作者：
Brander, Christian
影响因子：
2.2
作者：
Lalvani, A;Dong, T;Rowland-Jones, S
通讯作者：
Rowland-Jones, S
影响因子：
64.8
作者：
Klenerman, P;Zinkernagel, RM
通讯作者：
Zinkernagel, RM