公开(公告)号：US20120294879A1

公开(公告)日：2012-11-22

申请号：US13501339

申请日：2010-10-13

申请人： J. Thomas August ,  Paul ThiamJoo Tan ,  Tin Wee Tan ,  Mohammad Asif Khan

发明人： J. Thomas August ,  Paul ThiamJoo Tan ,  Tin Wee Tan ,  Mohammad Asif Khan

IPC分类号： A61K39/145 ,  C12N15/33 ,  C12N15/85 ,  C12N15/86 ,  C07K14/11 ,  C12P21/02 ,  C07K7/06 ,  A61P31/16 ,  C07K19/00 ,  C07K7/08 ,  C12N15/62 ,  C12N5/10

CPC分类号： A61K39/145 ,  A61K39/12 ,  A61K2039/5154 ,  A61K2039/5156 ,  A61K2039/70 ,  C07K14/005 ,  C07K2319/00 ,  C12N2760/16122 ,  C12N2760/16134

摘要： Pandemic A(H1N1) continues its global spread, and vaccine production is a serious problem. Protection by current vaccines is limited by the mutational differences that rapidly accumulate in the circulating strains, especially in the virus surface proteins. New vaccine strategies are focusing at conserved regions of the viral internal proteins to produce T cell epitope-based vaccines. T cell responses have been shown to reduce morbidity and promote recovery in mouse models of influenza challenge. We previously reported 54 highly conserved sequences of NP, M1 and the polymerases of all human H1N1, H3N2, H1N2, and H5N1, and avian subtypes over the past 30 years. Sixty-three T cell epitopes elicited responses in HLA transgenic mice (A2, A24, B7, DR2, DR3 and DR4). These epitopes were compared to the 2007-2009 human H1N1 sequences to identify conserved and variant residues. Seventeen T cell epitopes of PB1, PB2, and M1 were selected as vaccine targets by analysis of sequence conservation and variability, functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. The vaccines composed of these epitopes, being highly conserved and temporally stable, would be useful for any avian or human influenza A virus.

摘要翻译： 大流行A（H1N1）继续全球蔓延，疫苗生产是一个严重的问题。 目前疫苗的保护受到循环菌株尤其是病毒表面蛋白质快速积累的突变差异的限制。 新的疫苗策略着重于病毒内部蛋白质的保守区域，以产生基于T细胞表位的疫苗。 已经显示T细胞应答降低发病率并促进小鼠流感病毒模型的恢复。 以前报道过去30年来，54种高度保守的NP，M1和所有人类H1N1，H3N2，H1N2和H5N1以及禽亚型的聚合酶序列。 六十三个T细胞表位在HLA转基因小鼠（A2，A24，B7，DR2，DR3和DR4）中引发反应。 将这些表位与2007-2009年人类H1N1序列进行比较，以鉴定保守和变异残基。 通过分析序列保守性和可变性，功能亲合力，与人肽的非同一性，聚类定位和对多个HLA等位基因的混杂，选择PB1，PB2和M1的17个T细胞表位作为疫苗靶。 由这些表位组成的高度保守和时间稳定的疫苗对于任何禽类或人类甲型流感病毒都是有用的。

公开(公告)号：US20130195904A1

公开(公告)日：2013-08-01

申请号：US13520388

申请日：2011-01-04

申请人： J. Thomas August ,  Gregory George Simon ,  Tin Wee Tan ,  Asif Mohammad Khan ,  Hu Yongli

发明人： J. Thomas August ,  Gregory George Simon ,  Tin Wee Tan ,  Asif Mohammad Khan ,  Hu Yongli

IPC分类号： A61K39/21

CPC分类号： A61K39/21 ,  A61K39/00 ,  C07K14/005 ,  C12N2740/16022 ,  C12N2740/16034

摘要： We identified regions of the HIV-1 proteome with high conservation, and low variant incidence. Such highly conserved sequences have direct relevance to the development of new-generation vaccines and diagnostic applications. The immune relevance of these sequences was assessed by their correlation to previously reported human T-cell epitopes and to recently identified human HIV-1 T-cell epitopes (identified using HLA transgenic mice). We identified (a) sequences specific to HIV-1 with no shared identity to other viruses and organisms, and (b) sequences that are specific to primate lentivirus group, with multiclade HIV-1 conservation.

摘要翻译： 我们确定了具有高度保守性和低变异发生率的HIV-1蛋白质组的区域。 这种高度保守的序列与新一代疫苗和诊断应用的发展直接相关。 这些序列的免疫相关性通过与之前报道的人T细胞表位和最近鉴定的人HIV-1 T细胞表位（使用HLA转基因小鼠鉴定）的相关性来评估。 我们确定（a）HIV-1特异性序列，与其他病毒和生物体无共享身份，（b）具有多重HIV-1保护的灵长类慢病毒组特异性序列。

公开(公告)号：US20130011427A1

公开(公告)日：2013-01-10

申请号：US13516501

申请日：2010-12-16

申请人： J. Thomas August ,  Tin Wee Tan ,  Asif Mohammad Khan

发明人： J. Thomas August ,  Tin Wee Tan ,  Asif Mohammad Khan

IPC分类号： A61K39/12 ,  C12N15/40 ,  A61P37/04 ,  C12N5/10 ,  G01N33/53 ,  C07K7/06 ,  C12N15/63

CPC分类号： G01N33/56983 ,  A61K39/00 ,  C07K14/005 ,  C12N2770/24122 ,  G01N2333/18 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394 ,  Y02A50/53 ,  Y02A50/60

摘要： Flaviviruses represent an increasing global public health issue, with no prophylactic and therapeutic formulations currently available for many of them. The combination of factors such as evolutionary change, global warming and wide range of animal hosts suggest the possible occurrence of Flavivirus strains with greater distribution and human pathogenicity. There is, thus, a need for greater understanding of viral protein sequences that function in the human immune responses. The evolutionary diversity of the reported sequences of major flaviviruses, such as dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus were analyzed with a combination of experimental and bioinformatics methodologies. The analysis of all reported sequences revealed that these species-specific peptide tags are highly conserved and are potential T-cell epitopes due to correspondence to known or predicted epitopes. These peptide tags have direct relevance to the development of new-generation vaccines and diagnostic applications.

摘要翻译： 黄病毒属于日益严重的全球公共卫生问题，目前尚无许多预防和治疗方案。 诸如进化变化，全球变暖和广泛的动物宿主等因素的结合表明可能发生具有更大分布和人类致病性的黄病毒毒株。 因此，需要更多地了解在人免疫应答中起作用的病毒蛋白质序列。 通过实验和生物信息学方法的综合分析了报告的主要黄病毒序列的进化多样性，如登革热病毒，黄热病毒，日本脑炎病毒和西尼罗河病毒。 所有报道的序列的分析显示，这些物种特异性肽标签是高度保守的，并且由于与已知或预测的表位的对应而是潜在的T细胞表位。 这些肽标签与新一代疫苗和诊断应用的发展直接相关。