美国沃尔特里德陆军研究所Shelly J. Kreb、M. Gordon Joyce课题组的最新研究，通过对曾感染登革热病毒（DENV）的患者进行寨卡疫苗接种后可诱导得到有效的寨卡和登革热交叉中和抗体。这一研究成果2020年2月3日在线发表在国际学术期刊《自然—医学》上。

研究人员发现在感染过登革热病毒（DENV）的人中，使用单剂量ZIKV（寨卡病毒）纯化的灭活疫苗（ZPIV）可产生针对ZIKV和DENV的强效交叉中和抗体。利用一种针对ZIKV病毒独特的分类策略，研究人员分离并鉴定了多种抗体，其中包括一种名为MZ4的抗体，该抗体靶向位于膜糖蛋白（E）I / III结构域中心接头区域的新位点，在ZIKV或DENV-2感染后可以保护小鼠免受病毒败血症和病毒传播。这些数据表明，在感染过DENV的个体中接种Zika疫苗可以增强其已存在的针对黄病毒的免疫力，并引发针对ZIKV和DENV的保护性应答。对曾感染黄病毒的波多黎各人进行ZPIV疫苗接种后，单次接种后产生的交叉中和抗体具有相似效价，这凸显了ZIKV疫苗在黄病毒流行地区的潜在应用。

据悉，寨卡病毒可引起严重的疾病，并伴有神经病理学和先天性神经系统缺陷的特征。及时的疫苗开发已产生许多候选抗体其能够诱导产生有效的寨卡病毒中和抗体。尽管疫苗开发已取得了进展，但尚不清楚ZIKV疫苗接种是如何影响具有黄病毒免疫力人的免疫反应。

附：英文原文

Title: Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor

Author: Vincent Dussupt, Rajeshwer S. Sankhala, Gregory D. Gromowski, Gina Donofrio, Rafael A. De La Barrera, Rafael A. Larocca, Weam Zaky, Letzibeth Mendez-Rivera, Misook Choe, Edgar Davidson, Michael K. McCracken, James D. Brien, Peter Abbink, Hongjun Bai, Aubrey L. Bryan, Candace Hope Bias, Irina Maljkovic Berry, Nubia Botero, Tanya Cook, Nicole A. Doria-Rose, Ariadna Grinyo i Escuer, Justice Akuoku Frimpong, Aviva Geretz, Mayda Hernandez, Bradley S. Hollidge, Ningbo Jian, Kareem Kabra, David J. Leggat, Jinyan Liu, Amelia K. Pinto, Wiriya Rutvisuttinunt, Ian Setliff, Ursula Tran, Samantha Townsley, Benjamin J. Doranz, Morgane Rolland, Adrian B. McDermott, Ivelin S. Georgiev, Rasmi Thomas, Merlin L. Robb, Kenneth H. Eckels, Elizabeth Barranco, Michael Koren, Darci R. Smith, Richard G. Jarman, Sarah L. George, Kathryn E. Stephenson, Dan H. Barouch, Kayvon Modjarrad, Nelson L. Michael, M. Gordon Joyce, Shelly J. Krebs

Issue&Volume: 2020-02-03

Abstract: Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1,2,3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4,5,6,7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.

DOI: 10.1038/s41591-019-0746-2

Source: https://www.nature.com/articles/s41591-019-0746-2