Development of peptide-based vaccine against SARS-CoV

开发针对 SARS-CoV 的肽疫苗

• 批准号: 7603054
• 负责人: GANG LIU
• 金额: $ 34.27万
• 依托单位: INSTITUTE OF MATERIA MEDICA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603054
• 关键词: Achievement; Amino Acid Sequence; Amino Acids; Animal Model; Animals; Antibodies; Antigens; Antiviral Agents; B-Lymphocyte Epitopes; B-Lymphocytes; Carrier Proteins; Classification; Code; Combinatorial Synthesis; Communicable Diseases; Conjugated Carrier; Coronavirus; Country; Development; Diagnostic Procedure; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitopes; Evaluation; Genome Stability; Glycoproteins; Human; IL2 gene; Immunization; In Vitro; Individual; Interferon Type II; Interleukin-12; Length; Membrane Proteins; Methods; Patients; Peptide Library; Peptide Sequence Determination; Peptides; Peripheral Blood Mononuclear Cell; Proteins; Relative (related person); Serum; Severe Acute Respiratory Syndrome; System; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Testing; Vaccines; Viral; antibody conjugate; combinatorial; cytokine; design; env Gene Products; genome sequencing; immunogenicity; novel; peptide based vaccine; prevent; prophylactic; protein structure; response; therapeutic vaccine

DESCRIPTION (provided by applicant): Severe acute respiratory syndrome (SARS) caused by coronavirus is an emerging human infectious disease that epidemically spread worldwide. Therefore, the actual diagnostic method, preventing and therapeutic vaccine, and antiviral drugs are urgently demanded. This proposal aims at development of peptide-based vaccine including combinatorial synthesis of overlapped peptide library, identification of B- and T-cell epitopes directly, selection of neutralizing antigens and immunization of animal. 1.Using our coding and "MBGB" combinatorial technology, total 1938 overlapped individual peptides (10 amino acids in length) will be synthesized according to the BJ01 protein sequence including spike glycoprotein, membrane protein, envelope protein, and nucleocapasid protein, which potentially comprise the human immuno-recognizing domains of SARS CoV. 2. B-cell epitopes will be directly determined using ELISA method. The peptides reacted across with at least twelve antibody-positive sera of SARS patients will be determined as being positive. 3. SARS CoV specific T-cell epitopes from above proteins will be identified by peptide's stimulation of peripheral blood mononuclear cells (PBMC) releasing cytokines of recovered SARS patients, such as IFN-gamma, IL2, or IL12 detecting by Elispot method. 4. The elongated peptides covering two or three identified epitopes will be designed, synthesized and tested their antigenicity. Their immunogenicity will be determined when the anti-peptide (peptide-carrier conjugate) antibody from animal sera neutralizes the SARS CoV. 5. Multiple antigens containing both B-cell neutralizing antigens and SARS CoV specific T-cell epitopes will covalently conjugate onto protein carrier which will be able to immunize animals. The protection of SARS CoV challenges and CTL responses will be investigated to evaluate the peptide-based vaccine.

描述（由申请人提供）： 由冠状病毒引起的严重急性呼吸综合征（SARS）是一种新兴的人类传染病，在全球范围内传播。因此，迫切需要实际的诊断方法，预防和治疗性疫苗和抗病毒药物。该建议旨在开发基于肽的疫苗，包括重叠肽文库的组合合成，直接鉴定B-和T细胞表位，选择中和抗原的选择和动物免疫。 1.Using our coding and "MBGB" combinatorial technology, total 1938 overlapped individual peptides (10 amino acids in length) will be synthesized according to the BJ01 protein sequence including spike glycoprotein, membrane protein, envelope protein, and nucleocapasid protein, which potentially comprise the human immuno-recognizing domains of SARS CoV. 2。将使用ELISA方法直接确定B细胞表位。 SARS患者的至少十二种抗体阳性血清反应的肽将被确定为阳性。 3。通过肽刺激恢复的SARS患者的细胞因子（例如IFN-GAMMA，IL2，IL2或IL12检测）通过ELISPOT方法释放的细胞因子，可以通过肽刺激肽刺激肽刺激外周血单核细胞（PBMC）来鉴定SARS COV特异性T细胞表位。 4。将设计，合成并测试其抗原性的细长肽覆盖两个或三个鉴定的表位。当动物血清中和SARS COV的抗肽（肽 - 载体偶联物）抗体时，将确定它们的免疫原性。 5。多种含有B细胞中和抗原和SARS COV特异性T细胞表位的抗原将共价连接到蛋白质载体上，这将能够免疫动物。将研究对SARS COV挑战和CTL反应的保护，以评估基于肽的疫苗。

项目成果

A novel immunostimulator, N-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-trans-(m-nitrocinnamoyl)-L-lysine, and its adjuvancy on the hepatitis B surface antigen.

一种新型免疫刺激剂N-[α-O-苄基-N-(乙酰胞壁酰)-L-丙氨酰-D-异谷氨酰胺酰]-N6-反式-(间硝基肉桂酰)-L-赖氨酸及其在乙型肝炎表面的佐剂

• DOI: 10.1021/jm0493313
• 发表时间: 2005
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Yang,Hong-Zhen;Xu,Song;Liao,Xue-Yan;Zhang,Suo-De;Liang,Zheng-Lun;Liu,Bai-He;Bai,Jin-Ye;Jiang,Chao;Ding,Jian;Cheng,Gui-Fang;Liu,Gang
• 通讯作者: Liu,Gang