巴西和墨西哥出现的针对寨卡病毒的复发性强效人类中和抗体
Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.
作者信息
Robbiani Davide F, Bozzacco Leonia, Keeffe Jennifer R, Khouri Ricardo, Olsen Priscilla C, Gazumyan Anna, Schaefer-Babajew Dennis, Avila-Rios Santiago, Nogueira Lilian, Patel Roshni, Azzopardi Stephanie A, Uhl Lion F K, Saeed Mohsan, Sevilla-Reyes Edgar E, Agudelo Marianna, Yao Kai-Hui, Golijanin Jovana, Gristick Harry B, Lee Yu E, Hurley Arlene, Caskey Marina, Pai Joy, Oliveira Thiago, Wunder Elsio A, Sacramento Gielson, Nery Nivison, Orge Cibele, Costa Federico, Reis Mitermayer G, Thomas Neena M, Eisenreich Thomas, Weinberger Daniel M, de Almeida Antonio R P, West Anthony P, Rice Charles M, Bjorkman Pamela J, Reyes-Teran Gustavo, Ko Albert I, MacDonald Margaret R, Nussenzweig Michel C
机构信息
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
出版信息
Cell. 2017 May 4;169(4):597-609.e11. doi: 10.1016/j.cell.2017.04.024.
Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.
寨卡病毒（ZIKV）抗体具有保护作用。为了研究产生高滴度抗寨卡病毒抗体的个体的抗体反应，我们在巴西和墨西哥对人群进行筛查，检测其对寨卡病毒包膜结构域III（ZEDIII）的结合及中和能力。我们发现，寨卡病毒暴露前对登革热1型病毒（DENV1）包膜结构域III（EDIII）的血清学反应性与暴露后寨卡病毒中和滴度的增加相关。抗体克隆显示，具有高寨卡病毒中和抗体滴度的供体，其记忆B细胞中表达相同免疫球蛋白VH3-23/VK1-5基因的克隆有所扩增。这些反复出现的抗体与DENV1发生交叉反应，但不与其他黄病毒发生交叉反应，能中和DENV1和寨卡病毒，并保护小鼠免受寨卡病毒攻击。结构分析揭示了VH3-23/VK1-5抗体识别ZEDIII外侧脊的机制。血清学检测表明，针对该区域的抗体与血清对寨卡病毒的中和活性相关。因此，人类对寨卡病毒的高中和反应与先前对DENV1的反应性有关。
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