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含有塞姆利基森林病毒B和T细胞表位的合成肽的免疫原性及疫苗效力

Immunogenicity and vaccine efficacy of synthetic peptides containing Semliki Forest virus B and T cell epitopes.

作者信息

Snijders A, Benaissa-Trouw B J, Snippe H, Kraaijeveld C A

机构信息

Eijkman-Winkler Laboratory of Medical Microbiology, Academic Hospital Utrecht, The Netherlands.

出版信息

J Gen Virol. 1992 Sep;73 ( Pt 9):2267-72. doi: 10.1099/0022-1317-73-9-2267.

DOI:10.1099/0022-1317-73-9-2267
PMID:1383405
Abstract

A synthetic peptide that contains a Semliki Forest virus (SFV) B cell epitope, located at amino acid positions 240 to 255 of the E2 protein, and an SFV T helper (Th) cell epitope, located at positions 137 to 151 of the E2 protein, evoked high titres of SFV-reactive antibodies in H-2d mice. Although the peptide-induced antibodies did not neutralize SFV in vitro, 70 to 100% of the peptide-immunized mice were protected against SFV, even when viral challenge was presented 4 months after immunization. The protection could be transferred by anti-peptide serum, indicating that antibodies were responsible for the protection. When the Th cell epitope of this protective peptide was replaced by an influenza virus Th cell epitope or by another SFV Th cell epitope, the resulting peptides induced lower non-neutralizing SFV-reactive antibody titres and protected a correspondingly lower percentage of mice (50% and 30%, respectively). A peptide with the same Th cell epitope as the best protective peptide but with a less effective SFV B cell epitope protected only 33% of the mice. These results indicate that protection against SFV by a synthetic peptide is primarily dependent on its ability to induce adequate amounts of antibodies with relevant specificity and sufficient affinity; the ability to induce a relevant (SFV-specific) T memory response played only a minor role in protection.

摘要

一种合成肽,其包含位于E2蛋白氨基酸位置240至255的Semliki森林病毒(SFV)B细胞表位和位于E2蛋白位置137至151的SFV辅助性T(Th)细胞表位,可在H-2d小鼠中引发高滴度的SFV反应性抗体。尽管该肽诱导的抗体在体外不能中和SFV,但70%至100%经该肽免疫的小鼠可免受SFV感染,即使在免疫后4个月进行病毒攻击时也是如此。这种保护作用可通过抗肽血清转移,表明抗体是起保护作用的原因。当该保护性肽的Th细胞表位被流感病毒Th细胞表位或另一个SFV Th细胞表位取代时,所得肽诱导产生的非中和性SFV反应性抗体滴度较低,相应地保护的小鼠百分比也较低(分别为50%和30%)。一种与最佳保护性肽具有相同Th细胞表位但SFV B细胞表位效果较差的肽仅保护了33%的小鼠。这些结果表明,合成肽对SFV的保护作用主要取决于其诱导足够量具有相关特异性和足够亲和力的抗体的能力;诱导相关(SFV特异性)T记忆反应的能力在保护中仅起次要作用。

相似文献

1
Immunogenicity and vaccine efficacy of synthetic peptides containing Semliki Forest virus B and T cell epitopes.含有塞姆利基森林病毒B和T细胞表位的合成肽的免疫原性及疫苗效力
J Gen Virol. 1992 Sep;73 ( Pt 9):2267-72. doi: 10.1099/0022-1317-73-9-2267.
2
A delayed-type hypersensitivity-inducing T-cell epitope of Semliki Forest virus mediates effective T-helper activity for antibody production.塞姆利基森林病毒的一种迟发型超敏反应诱导性T细胞表位介导抗体产生的有效辅助性T细胞活性。
Immunology. 1992 Nov;77(3):322-9.
3
Influence of epitope polarity and adjuvants on the immunogenicity and efficacy of a synthetic peptide vaccine against Semliki Forest virus.表位极性和佐剂对一种抗塞姆利基森林病毒合成肽疫苗免疫原性和效力的影响。
J Virol. 1993 Oct;67(10):5843-8. doi: 10.1128/JVI.67.10.5843-5848.1993.
4
Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine.塞姆利基森林病毒E2膜蛋白线性表位的鉴定及其作为合成肽疫苗的有效性
J Gen Virol. 1991 Mar;72 ( Pt 3):557-65. doi: 10.1099/0022-1317-72-3-557.
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A vaccine against Semliki Forest virus consisting of a monoclonal anti-idiotypic antibody cross-linked to a protein which contains virus-specific T-helper cell epitopes.一种针对塞姆利基森林病毒的疫苗,由与含有病毒特异性辅助性T细胞表位的蛋白质交联的单克隆抗独特型抗体组成。
Antiviral Res. 1992 Oct 1;19(4):275-84. doi: 10.1016/0166-3542(92)90009-t.
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Semliki Forest virus E2 envelope epitopes induce a nonneutralizing humoral response which protects mice against lethal challenge.Semliki森林病毒E2包膜表位诱导一种非中和性体液反应,可保护小鼠免受致死性攻击。
J Virol. 1989 Aug;63(8):3416-22. doi: 10.1128/JVI.63.8.3416-3422.1989.
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Epitope polarity and adjuvants influence the fine specificity of the humoral response against Semliki Forest virus specific peptide vaccines.表位极性和佐剂影响针对塞姆利基森林病毒特异性肽疫苗的体液免疫反应的精细特异性。
Vaccine. 1998 Oct;16(16):1531-6. doi: 10.1016/s0264-410x(98)00038-3.
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A shared idiotope among antibodies against Semliki Forest virus.抗Semliki森林病毒抗体间的共同独特型。
Viral Immunol. 1994;7(2):71-80. doi: 10.1089/vim.1994.7.71.
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Peptide vaccines incorporating a 'promiscuous' T-cell epitope bypass certain haplotype restricted immune responses and provide broad spectrum immunogenicity.包含“混杂”T细胞表位的肽疫苗可绕过某些单倍型受限的免疫反应,并提供广谱免疫原性。
J Mol Recognit. 1993 Jun;6(2):81-94. doi: 10.1002/jmr.300060206.
10
Delineation of protective epitopes on the E2-envelope glycoprotein of Semliki Forest virus.
Vaccine. 1991 Jun;9(6):451-6. doi: 10.1016/0264-410x(91)90134-r.

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J Neuroimmunol. 2011 Jun;235(1-2):18-26. doi: 10.1016/j.jneuroim.2011.02.013. Epub 2011 May 25.
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Influence of epitope polarity and adjuvants on the immunogenicity and efficacy of a synthetic peptide vaccine against Semliki Forest virus.表位极性和佐剂对一种抗塞姆利基森林病毒合成肽疫苗免疫原性和效力的影响。
J Virol. 1993 Oct;67(10):5843-8. doi: 10.1128/JVI.67.10.5843-5848.1993.