VP4- and VP7-specific antibodies mediate heterotypic immunity to rotavirus in humans.
VP4- and VP7-specific antibodies mediate heterotypic immunity to rotavirus in humans.
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DOI：
10.1126/scitranslmed.aam5434
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发表时间：
2017-06-21
影响因子：
17.1
通讯作者：
Greenberg HB
中科院分区：
文献类型：
--
作者：
Nair N;Feng N;Blum LK;Sanyal M;Ding S;Jiang B;Sen A;Morton JM;He XS;Robinson WH;Greenberg HB
人类轮状病毒（RV）是全球幼儿严重腹泻的主要原因。快速诱导对RV的异型保护性免疫的分子机制，为获得许可的单价RV疫苗的有效性提供了基础，30多年来仍然未知。我们使用来自成人的RV特异性单细胞分选的肠B细胞、基于条形码的抗体库深度测序、单克隆抗体表达以及血清学和功能表征来证明感染诱导的异型免疫球蛋白（Ig）主要针对RV附着蛋白VP 4的茎区VP 5 *，能够介导异型保护性免疫。针对VP 7（衣壳糖蛋白）和VP 8 *（VP 4的细胞结合区）的异型保护性Ig在感染后也会产生;然而，我们的数据表明，同型抗VP 7和非中和性VP 8 * 反应在人群中更常见。这些结果表明，人类可以通过在自然感染后对VP 7、VP 8 * 和最常见的VP 5 * 产生频繁的异型中和抗体应答来规避循环RV毒株的广泛血清型多样性。这些发现进一步表明，重组VP 5 * 可能是一个有用的目标，为发展一个改进的，第三代，广泛有效的RV疫苗，并保证更直接的检查。
Human rotaviruses (RVs) are the leading cause of severe diarrhea in young children worldwide. The molecular mechanisms underlying the rapid induction of heterotypic protective immunity to RV, which provides the basis for the efficacy of licensed monovalent RV vaccines, have remained unknown for more than 30 years. We used RV-specific single cell–sorted intestinal B cells from human adults, barcode-based deep sequencing of antibody repertoires, monoclonal antibody expression, and serologic and functional characterization to demonstrate that infection-induced heterotypic immunoglobulins (Igs) primarily directed to VP5*, the stalk region of the RV attachment protein, VP4, are able to mediate heterotypic protective immunity. Heterotypic protective Igs against VP7, the capsid glycoprotein, and VP8*, the cell-binding region of VP4, are also generated after infection; however, our data suggest that homotypic anti-VP7 and non-neutralizing VP8* responses occur more commonly in people. These results indicate that humans can circumvent the extensive serotypic diversity of circulating RV strains by generating frequent heterotypic neutralizing antibody responses to VP7, VP8*, and most often, to VP5* after natural infection. These findings further suggest that recombinant VP5* may represent a useful target for the development of an improved, third-generation, broadly effective RV vaccine and warrants more direct examination.
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影响因子：
56.9
作者：
Burns, JW;SiadatPajouh, M;Greenberg, HB
通讯作者：
Greenberg, HB
影响因子：
3.7
作者：
Lanata CF;Fischer-Walker CL;Olascoaga AC;Torres CX;Aryee MJ;Black RE;Child Health Epidemiology Reference Group of the World Health Organization and UNICEF
通讯作者：
Child Health Epidemiology Reference Group of the World Health Organization and UNICEF
影响因子：
64.8
作者：
Dormitzer, PR;Nason, EB;Harrison, SC
通讯作者：
Harrison, SC
影响因子：
9.4
作者：
MATSUI, SM;OFFIT, PA;GREENBERG, HB
通讯作者：
GREENBERG, HB
DOI：
10.1126/science.1170481
发表时间：
2009-06-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aoki ST;Settembre EC;Trask SD;Greenberg HB;Harrison SC;Dormitzer PR
通讯作者：
Dormitzer PR