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一种新型合成脂肽口蹄疫病毒疫苗α-螺旋表位的分子动力学

Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.

作者信息

Krug M, Folkers G, Haas B, Hess G, Wiesmüller K H, Freund S, Jung G

出版信息

Biopolymers. 1989 Jan;28(1):499-512. doi: 10.1002/bip.360280144.

DOI:10.1002/bip.360280144
PMID:2470437
Abstract

A novel synthetic foot-and-mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B-cell and macrophage activator covalently linked to an amphiphilic alpha-helical T-cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-serine (P3CSS) as built-in adjuvant. The vaccine, tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl-FMDV-VP1 (VP1 = serotype O1K 135-154) induces protection against homologous challenge and serotype-specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV-VP1 segment 135-154 of strain O Wuppertal produced only poor cross-protection against challenge with O1K virus. The antigenic determinant VP1(135-154) is an amphiphilic alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-helical conformation during binding to its T-cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex.

摘要

开发了一种新型合成口蹄疫病毒（FMDV）肽疫苗，该疫苗由与两亲性α-螺旋T细胞表位共价连接的合成B细胞和巨噬细胞激活剂组成。这种分子量为3400道尔顿的低分子量疫苗由病毒VP1抗原决定簇和具有免疫活性的脂三肽三棕榈酰-S-甘油基-半胱氨酰-丝氨酰-丝氨酸（P3CSS）作为内置佐剂组成。该疫苗，三棕榈酰-S-甘油基-半胱氨酰-丝氨酰-丝氨酰-FMDV-VP1（VP1 = O1K血清型135 - 154）在单次给药后，无需进一步的佐剂或载体，就能在豚鼠中诱导针对同源攻击的保护作用和血清型特异性病毒中和抗体。P3CSS与伍珀塔尔O株FMDV-VP1片段135 - 154的缀合物对O1K病毒攻击仅产生较差的交叉保护作用。如圆二色光谱所示，抗原决定簇VP1(135 - 154)是一种两亲性α-螺旋。使用高度同源的α-螺旋醇脱氢酶（ADH）片段H3作为VP1(138 - 149)的起始构象进行的分子动力学模拟（MDS）表明，FMDV片段138 - 149在与其T细胞受体结合过程中可能采用α-螺旋构象，并且MDS过程中系统的发展可被视为复合物的解离步骤。

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1
Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.一种新型合成脂肽口蹄疫病毒疫苗α-螺旋表位的分子动力学
Biopolymers. 1989 Jan;28(1):499-512. doi: 10.1002/bip.360280144.
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Novel low-molecular-weight synthetic vaccine against foot-and-mouth disease containing a potent B-cell and macrophage activator.
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Conformational preferences of a peptide corresponding to the major antigenic determinant of foot-and-mouth disease virus: implications for peptide-vaccine approaches.口蹄疫病毒主要抗原决定簇对应肽段的构象偏好性：对肽疫苗方法的启示
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A 10-amino-acid linear sequence of VP1 of foot and mouth disease virus containing B- and T-cell epitopes induces protection in mice.口蹄疫病毒VP1的一段含B细胞和T细胞表位的10个氨基酸线性序列可诱导小鼠产生保护作用。
Virology. 1995 Oct 1;212(2):614-21. doi: 10.1006/viro.1995.1519.
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Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV peptides after vaccination or immunization with these peptides in cattle.牛接种口蹄疫病毒或三种口蹄疫病毒肽疫苗后，对这些肽的增殖性淋巴细胞反应。
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[Antigenic structure of the foot-and-mouth virus. VI. Functional segments of the immunodominant region of the VP1 protein of foot-and-mouth virus strains O1K and A22].[口蹄疫病毒的抗原结构。VI. O1K和A22口蹄疫病毒株VP1蛋白免疫显性区的功能片段]
Bioorg Khim. 1991 May;17(5):596-605.
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[Antigenic structure of the foot-and-mouth disease virus. III. Immunogenic properties of synthetic peptides of the sequence of the immunodominant region of VP1 proteins of the O1K and A22 strains of foot-and-mouth virus].[口蹄疫病毒的抗原结构。III. 口蹄疫病毒O1K和A22株VP1蛋白免疫显性区序列合成肽的免疫原性]
Bioorg Khim. 1989 Sep;15(9):1185-92.
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Recognition of B and T cell epitopes by cattle immunized with a synthetic peptide containing the major immunogenic site of VP1 FMDV 01 Campos.用含有口蹄疫病毒01坎波斯株VP1主要免疫原性位点的合成肽免疫牛后对B细胞和T细胞表位的识别
Virology. 1994 Jun;201(2):383-7. doi: 10.1006/viro.1994.1305.
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[Synthetic peptides simulating the protective epitopes of VP1 protein of foot-and-mouth disease virus type O and A].[模拟O型和A型口蹄疫病毒VP1蛋白保护性表位的合成肽]
Bioorg Khim. 1987 Aug;13(8):1132-5.
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DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses.表达B细胞和T细胞表位的DNA疫苗能够在缺乏特异性体液免疫反应的情况下保护小鼠免受口蹄疫病毒感染。
Vaccine. 2006 May 1;24(18):3889-99. doi: 10.1016/j.vaccine.2006.02.028. Epub 2006 Mar 3.

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