Cross-Subtype Neutralization Sensitivity despite Monoclonal Antibody Resistance among Early Subtype A, C, and D Envelope Variants of Human Immunodeficiency Virus Type 1
Cross-Subtype Neutralization Sensitivity despite Monoclonal Antibody Resistance among Early Subtype A, C, and D Envelope Variants of Human Immunodeficiency Virus Type 1
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DOI：
10.1128/jvi.00673-09
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发表时间：
2009-08-01
影响因子：
5.4
通讯作者：
Overbaugh, Julie
中科院分区：
文献类型：
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作者：
Blish, Catherine A.;Jalalian-Lechak, Zahra;Overbaugh, Julie
传染给新感染者的人类免疫缺陷病毒1型（HIV-1）变种是疫苗和杀微生物剂等干预措施的主要目标，旨在预防新的感染。新获得的A、B和C亚型变异体一直是中和研究的重点，尽管这些病毒中的许多，特别是A和B亚型，代表了十多年前流行的病毒。为了更好地代表全球传播的HIV-1变异体的多样性，另外31个性传播的肯尼亚HIV-1 env基因，代表最近感染的亚型A，以及亚型A/D，C和D，进行了克隆，并对其中和谱进行了表征。大多数env变异体对单克隆抗体（MAb）b12、4 E10、2F 5和2G 12的中和具有抗性，这表明靶向这些MAb的表位可能无法有效对抗在流行地区传播的变异体。然而，观察到血浆的显著交叉亚型中和，表明可能存在尚未由有限的可用MAb定义的其他表位，其可以被更广泛地识别。
The human immunodeficiency virus type 1 (HIV-1) variants that are transmitted to newly infected individuals are the primary targets of interventions, such as vaccines and microbicides, aimed at preventing new infections. Newly acquired subtype A, B, and C variants have been the focus of neutralization studies, although many of these viruses, particularly of subtypes A and B, represent viruses circulating more than a decade ago. In order to better represent the global diversity of transmitted HIV-1 variants, an additional 31 sexually transmitted Kenyan HIV-1 env genes, representing several recent infections with subtype A, as well as subtypes A/D, C, and D, were cloned, and their neutralization profiles were characterized. Most env variants were resistant to neutralization by the monoclonal antibodies (MAbs) b12, 4E10, 2F5, and 2G12, suggesting that targeting the epitopes of these MAbs may not be effective against variants that are spreading in areas of endemicity. However, significant cross-subtype neutralization by plasma was observed, indicating that there may be other epitopes, not yet defined by the limited available MAbs, which could be recognized more broadly.