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感染MN-rgp120疫苗接种志愿者的病毒的基因和免疫特征

Genetic and immunologic characterization of viruses infecting MN-rgp120-vaccinated volunteers.

作者信息

Berman P W, Gray A M, Wrin T, Vennari J C, Eastman D J, Nakamura G R, Francis D P, Gorse G, Schwartz D H

机构信息

Department of Process Sciences, Genentech, Inc., South San Francisco, California 94080, USA.

出版信息

J Infect Dis. 1997 Aug;176(2):384-97. doi: 10.1086/514055.

DOI:10.1086/514055
PMID:9237703
Abstract

Proviral sequences were determined and immunologic characterization was carried out for envelope glycoproteins from 7 vaccinees who became infected with human immunodeficiency virus type 1 (HIV-1), through high-risk behavior, while participating in clinical trials of MN-rgp120, a candidate HIV-1 vaccine. All 7 infections resulted from subtype B viruses; however, only 3 of the viruses possessed the MN serotype-defining V3 domain sequence, IGPGRAF, prevalent in 60%-70% of US infections. Six of the 7 viruses differed from MN-rgp120 at a neutralizing epitope in the C4 domain, and all 7 differed from MN-rgp120 at a neutralizing epitope in the V2 domain. Recombinant gp120 was prepared from each breakthrough specimen and tested for binding to a panel of neutralizing monoclonal antibodies. The results suggest that 6 of 7 breakthrough infections may be related to incomplete immunization or to infection with viruses that differed from the vaccine immunogen at important virus-neutralizing epitopes.

摘要

对7名在参与HIV-1候选疫苗MN-rgp120的临床试验期间因高危行为感染1型人类免疫缺陷病毒(HIV-1)的疫苗接种者的前病毒序列进行了测定,并对其包膜糖蛋白进行了免疫学特征分析。所有7例感染均由B亚型病毒引起;然而,只有3种病毒具有MN血清型定义的V3结构域序列IGPGRAF,该序列在美国60%-70%的感染中普遍存在。7种病毒中有6种在C4结构域的一个中和表位上与MN-rgp120不同,并且所有7种病毒在V2结构域的一个中和表位上与MN-rgp120不同。从每个突破样本中制备重组gp120,并检测其与一组中和单克隆抗体的结合情况。结果表明,7例突破感染中有6例可能与免疫接种不完全或与在重要病毒中和表位上与疫苗免疫原不同的病毒感染有关。

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