Early development of broadly neutralizing antibodies in HIV-1-infected infants

被引:134
作者
Goo, Leslie [1 ,2 ]
Chohan, Vrasha [1 ]
Nduati, Ruth [3 ]
Overbaugh, Julie [1 ,4 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA
[2] Univ Washington, Dept Global Hlth, Grad Program Pathobiol, Seattle, WA 98195 USA
[3] Univ Nairobi, Dept Pediat, Nairobi, Kenya
[4] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA
基金
美国国家卫生研究院;
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; DISEASE PROGRESSION; ENVELOPE VARIANTS; HIV-1; INFECTION; POTENT; SENSITIVITY; SUBTYPE; BREADTH;
D O I
10.1038/nm.3565
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting because of the extensive genetic and antigenic diversity of HIV-1. Moreover, broad and potent responses are uncommon even during persistent infection, with only a subset of adults developing broadly neutralizing antibodies (bNAbs) that recognize viral variants from different HIV-1 clades(1-8). It is not known whether bNAbs can also arise in HIV-1-infected infants, who typically progress to disease faster than adults(9), presumably in part due to an immature immune system(10). Here, we show that bNAbs develop at least as commonly in infants as in adults. Cross-clade NAb responses were detected in 20/28 infected infants, in some cases within 1 year of infection. Among infants with breadth of responses within the top quartile, neutralization of tier 2 or 3 variants from multiple clades was detected at 20 months after infection. These findings suggest that, even in early life, there is sufficient B cell functionality to mount bNAbs against HIV-1. Additionally, the relatively early appearance of bNAbs in infants. may provide a unique setting for understanding the pathways of B cell maturation leading to bNAbs.
引用
收藏
页码:655 / 658
页数:4
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