Innate, T-, and B-Cell Responses in Acute Human Zika Patients.
Innate, T-, and B-Cell Responses in Acute Human Zika Patients.
复制标题
DOI：
10.1093/cid/cix732
复制
发表时间：
2018-01-06
期刊：
影响因子：
--
通讯作者：
Emory Zika Patient Study Team
中科院分区：
文献类型：
--
作者：
Lai L;Rouphael N;Xu Y;Natrajan MS;Beck A;Hart M;Feldhammer M;Feldpausch A;Hill C;Wu H;Fairley JK;Lankford-Turner P;Kasher N;Rago P;Hu YJ;Edupuganti S;Patel SM;Murray KO;Mulligan MJ;Emory Zika Patient Study Team
了解人类急性寨卡病毒期间的免疫反应将有助于疫苗设计和测试。在5名急性患者中，包括2名孕妇，描述了针对寨卡病毒或登革热病毒的病毒水平和先天性、T细胞和B细胞应答。迫切需要研究人类寨卡病毒感染期间的病毒持续性和免疫力，以指导疫苗临床试验的规划和实施。在5名患有急性症状性寨卡病毒感染的美国旅行者中，对临床特征、病毒RNA水平和免疫反应进行了表征。两名怀孕的黄病毒感染患者的病毒RNA在血浆中持续时间分别为>44天和>26天。症状发作后3天，促炎性单核细胞开始短暂增加，随后在第5天髓样树突状细胞短暂减少。在症状发作后第7天检测到抗寨卡病毒免疫球蛋白M，持续超过103天，并在第172天保持不确定。寨卡病毒特异性浆母细胞和中和抗体迅速发展;登革热病毒特异性浆母细胞和高滴度的中和抗体仅在黄病毒感染患者中发展。寨卡病毒和登革病毒特异性记忆B细胞在未感染黄病毒和感染过黄病毒的患者中均出现。在4/4例患者中，在用寨卡病毒C、prM、E和NS 5肽刺激后，CD 4 + T细胞被中度活化并产生抗病毒细胞因子。相比之下，CD 8 + T细胞被大量激活，但仅在2/4的评估患者中存在产生细胞因子的病毒特异性细胞。寨卡病毒急性感染早期调节抗原呈递细胞群经历过黄病毒感染的患者很快就会回忆起交叉反应的MBC来分泌抗体。登革病毒初治患者几乎不产生登革特异性抗体，但产生了与登革病毒交叉反应的MBC。很容易检测到寨卡病毒特异性功能性CD 4 + T细胞，但很少发现对测试肽特异性的CD 8 + T细胞。
Understanding the immune response during acute Zika in humans will aid vaccine design and testing. In 5 acute patients, including 2 pregnant women, viral levels and innate, T-, and B-cell responses against Zika or dengue viruses are described. There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. In 5 returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset, transient increases in proinflammatory monocytes began followed at 5 days by transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M was detected at day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus–specific plasmablasts and neutralizing antibodies developed quickly; dengue virus–specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus– and dengue virus–specific memory B cells developed in both flavivirus-naive and -experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated, but virus-specific cells that produced cytokines were present in only 2/4 patients assessed. Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus–naive patients made little dengue-specific antibody but developed MBCs that cross-reacted against dengue virus. Zika virus–specific functional CD4+ T cells were readily detected, but few CD8+ T cells specific for the tested peptides were found.
登录
查看更多内容
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
5.4
作者：
Chandele A;Sewatanon J;Gunisetty S;Singla M;Onlamoon N;Akondy RS;Kissick HT;Nayak K;Reddy ES;Kalam H;Kumar D;Verma A;Panda H;Wang S;Angkasekwinai N;Pattanapanyasat K;Chokephaibulkit K;Medigeshi GR;Lodha R;Kabra S;Ahmed R;Murali-Krishna K
通讯作者：
Murali-Krishna K
影响因子：
8.8
作者：
Dowd KA;DeMaso CR;Pelc RS;Speer SD;Smith ARY;Goo L;Platt DJ;Mascola JR;Graham BS;Mulligan MJ;Diamond MS;Ledgerwood JE;Pierson TC
通讯作者：
Pierson TC
DOI：
10.1126/science.aah6157
发表时间：
2016-09-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abbink P;Larocca RA;De La Barrera RA;Bricault CA;Moseley ET;Boyd M;Kirilova M;Li Z;Ng'ang'a D;Nanayakkara O;Nityanandam R;Mercado NB;Borducchi EN;Agarwal A;Brinkman AL;Cabral C;Chandrashekar A;Giglio PB;Jetton D;Jimenez J;Lee BC;Mojta S;Molloy K;Shetty M;Neubauer GH;Stephenson KE;Peron JP;Zanotto PM;Misamore J;Finneyfrock B;Lewis MG;Alter G;Modjarrad K;Jarman RG;Eckels KH;Michael NL;Thomas SJ;Barouch DH
通讯作者：
Barouch DH
DOI：
10.4269/ajtmh.2012.12-0179
发表时间：
2013-01-01
影响因子：
3.3
作者：
Edupuganti, Srilatha;Eidex, Rachel B.;Mulligan, Mark J.
通讯作者：
Mulligan, Mark J.