High prevalence of neutralizing activity against multiple unrelated human immunodeficiency virus type 1 (HIV-1) subtype B variants in sera from HIV-1 subtype B-infected individuals: evidence for subtype-specific rather than strain-specific neutralizing ac
High prevalence of neutralizing activity against multiple unrelated human immunodeficiency virus type 1 (HIV-1) subtype B variants in sera from HIV-1 subtype B-infected individuals: evidence for subtype-specific rather than strain-specific neutralizing ac
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HIV-1 B 亚型感染者血清中针对多种不相关的人类免疫缺陷病毒 1 型 (HIV-1) B 亚型变体的中和活性普遍存在：亚型特异性而非毒株特异性中和活性的证据
DOI：
10.1099/vir.0.015693-0
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Schuitemaker,Hanneke
中科院分区：
文献类型：
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作者：
vanGils,MaritJ;Edo-Matas,Diana;Schweighardt,Becky;Wrin,Terri;Schuitemaker,Hanneke
据推测，有效的人类免疫缺陷病毒1型（HIV-1）疫苗应能够引发中和抗体。然而，即使是迄今为止已知的最好的抗体也缺乏针对相当大比例的主要HIV-1变体的中和能力，并且尽管做出了巨大努力，仍然没有可以引发体液免疫的免疫原可用，所述体液免疫可以保护免受感染或疾病进展。我们检测了来自阿姆斯特丹HIV-1感染队列研究的35名参与者的血清，这些参与者在采样时均感染了HIV-1 B亚型且未接受过治疗，检测了对一组2 - 3种2-3级HIV-1变体的中和活性，每种亚型至少有5种HIV-1变体（A、B、C和D）。在来自7个个体的血清中检测到强的跨进化枝中和活性。引人注目的是，来自35个个体中的22个（63%）的血清中和了组中的六种2-3级HIV-1亚型B病毒中的三种或更多种。 血清中和滴度与中和宽度之间有很强的相关性。实际上，具有强交叉进化枝中和活性的血清的IC 50显著高于具有交叉亚型B活性的血清的IC 50，而具有交叉亚型B活性的血清的IC 50又高于具有最低中和宽度的血清。这些结果表明，体液免疫，至少在HIV-1亚型B感染的个人，往往是亚型特异性的，而不是菌株特异性和中和的宽度与血清中的中和活性滴度。考虑到设计能够引起交叉进化枝中和活性的疫苗的困难，亚型特异性疫苗可以作为一种有趣的替代方案进行探索。
It is assumed that an effective human immunodeficiency virus type 1 (HIV-1) vaccine should be capable of eliciting neutralizing antibodies. However, even the best antibodies known to date lack neutralizing ability against a significant proportion of primary HIV-1 variants and, despite great efforts, still no immunogen is available that can elicit humoral immunity which is protective against infection or disease progression. We tested sera from 35 participants in the Amsterdam Cohort Studies on HIV-1 infection, who were all infected with HIV-1 subtype B and therapy-naïve at the time of sampling, for neutralizing activity against a panel of 23 tier 2–3 HIV-1 variants, with a minimum of five HIV-1 variants per subtype (A, B, C and D). Strong cross-clade neutralizing activity was detected in sera from seven individuals. Strikingly, sera from 22 of 35 individuals (63 %) neutralized three or more of the six tier 2–3 HIV-1 subtype B viruses in the panel. There was a strong correlation between neutralization titre and breadth in serum. Indeed, the IC50of sera with strong cross-clade neutralizing activity was significantly higher than the IC50of sera with cross-subtype B activity, which, in turn, had a higher IC50than sera with the lowest neutralization breadth. These results imply that humoral immunity, at least in HIV-1 subtype B-infected individuals, is often subtype-specific rather than strain-specific and that the breadth of neutralization is correlated with the titre of neutralizing activity in serum. Considering the difficulties in designing a vaccine that is capable of eliciting cross-clade neutralizing activity, subtype-specific vaccines may be explored as an interesting alternative.