EPITOPE MAPPING OF JAPANESE ENCEPHALITIS-VIRUS ENVELOPE PROTEIN USING MONOCLONAL-ANTIBODIES AGAINST AN INDIAN STRAIN

EPITOPE MAPPING OF JAPANESE ENCEPHALITIS-VIRUS ENVELOPE PROTEIN USING MONOCLONAL-ANTIBODIES AGAINST AN INDIAN STRAIN
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DOI:
10.1099/0022-1317-69-11-2741
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发表时间:
1988-11-01
影响因子:
3.8
通讯作者:
GHOSH, SN
GHOSH, SN
中科院分区:
医学3区
文献类型:
--
作者:
CECILIA, D;GADKARI, DA;GHOSH, SN

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使用一组针对印度流行性乙型脑炎(JE)病毒株的单克隆抗体(MAb)来对包膜蛋白上的表位进行地形图绘制。揭示了两个独立的表位簇。根据单克隆抗体在血凝抑制(HI)、中和(NT)、被动保护和抗体依赖性空斑增强(ADPE)试验中的反应性,划分了5个功能域(A、B、C、D和E)。黄病毒对HI(A)的交叉反应域是不同的。HI(B)的JE病毒特异性结构域与代表非HI JE病毒特异性MAb(C)和黄病毒交叉反应性MAb(D)的那些结构域是连续的。结构域E,其映射接近结构域D,由与乙脑病毒和未感染的细胞核反应的两个单克隆抗体表示。可以得出四个结论。(i)两个不同的抗原结构域与HI,(ii)HI和NT在体内和体外分离的功能,(iii)ADPE活性仅与A结构域和(iv)所有单克隆抗体反应的抗原决定簇在B域有HI/NT/保护活性,但未能显示ADPE。因此,B结构域可能被认为最适合于开发合成或遗传工程疫苗。
A panel of monoclonal antibodies (MAbs) raised against an Indian strain of Japanese encephalitis (JE) virus was used to map topographically the epitopes on the envelope protein. Two separate clusters of epitopes were revealed. On the basis of reactivity in haemagglutination inhibition (HI), neutralization (NT), passive protection and antibody-dependent plaque enhancement (ADPE) assays with the MAbs, five functional domains (A, B, C, D and E) were delineated. The flavivirus cross-reactive domain for HI (A) was distinct. The JE virus-specific domain for HI (B) was in continuum with those domains representing non-HI JE virus-specific MAbs (C) and flavivirus cross-reactive MAbs (D). Domain E, which mapped close to domain D was represented by two MAbs that reacted with both JE virus and uninfected cell nuclei. Four conclusions can be drawn. (i) Two distinct antigenic domains were associated with HI, (ii) HI and NT in vivo and in vitro were dissociated functions, (iii) ADPE activity was solely linked with the A domain and (iv) all MAbs reacting with epitopes in the B domain had HI/NT/protective activity but failed to show ADPE. The B domain might therefore be considered the most suitable for development of synthetic or genetically engineered vaccines.