Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice.
Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice.
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DOI：
10.3389/fimmu.2021.686411
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lim JK
中科院分区：
文献类型：
--
作者：
Acklin JA;Cattle JD;Moss AS;Brown JA;Foster GA;Krysztof D;Stramer SL;Lim JK
抗体依赖性增强（ADE）是当先前的黄病毒感染产生的交叉反应性抗体增加相关病毒的发病机制时发生的一种现象。寨卡病毒 (ZIKV) 是最近引入西半球的黄病毒，由于对发育中的胎儿产生意想不到的影响，已成为重大的公共卫生威胁。西尼罗河病毒 (WNV) 是在北美传播的主要黄病毒，我们和其他人已经证明，针对 WNV 的抗体与 ZIKV 存在交叉反应。因此，人们担心西尼罗河病毒免疫可能会增加严重寨卡病毒感染的风险，特别是在怀孕期间。在这项研究中，我们在小鼠妊娠模型中研究了 WNV 抗体对 ZIKV 发病机制的影响程度。为了测试这一点，我们在 E6.5 感染 ZIKV 之前将 WNV 抗体被动转移到怀孕的 Stat2-/- 小鼠中。对怀孕母鼠的评估显示，寨卡病毒感染后体重减轻；然而，在存在西尼罗河病毒抗体的情况下，没有观察到母体体重或母体大脑、脾脏或脊髓中病毒载量的差异。吸收率和其他胎儿参数，包括胎儿和胎盘大小，同样不受影响。此外，WNV 抗体的存在并没有显着改变病毒载量或胎盘或胎儿对 ZIKV 的炎症反应。我们的数据表明，预先存在的西尼罗河病毒免疫可能不会显着影响妊娠期间寨卡病毒感染的发病机制。我们的研究结果对于在美国大陆实施西尼罗河病毒疫苗的安全性来说是有希望的。
Antibody-dependent enhancement (ADE) is a phenomenon that occurs when cross-reactive antibodies generated from a previous flaviviral infection increase the pathogenesis of a related virus. Zika virus (ZIKV) is the most recent flavivirus introduced to the Western Hemisphere and has become a significant public health threat due to the unanticipated impact on the developing fetus. West Nile virus (WNV) is the primary flavivirus that circulates in North America, and we and others have shown that antibodies against WNV are cross-reactive to ZIKV. Thus, there is concern that WNV immunity could increase the risk of severe ZIKV infection, particularly during pregnancy. In this study, we examined the extent to which WNV antibodies could impact ZIKV pathogenesis in a murine pregnancy model. To test this, we passively transferred WNV antibodies into pregnant Stat2-/- mice on E6.5 prior to infection with ZIKV. Evaluation of pregnant dams showed weight loss following ZIKV infection; however, no differences in maternal weights or viral loads in the maternal brain, spleen, or spinal cord were observed in the presence of WNV antibodies. Resorption rates, and other fetal parameters, including fetal and placental size, were similarly unaffected. Further, the presence of WNV antibodies did not significantly alter the viral load or the inflammatory response in the placenta or the fetus in response to ZIKV. Our data suggest that pre-existing WNV immunity may not significantly impact the pathogenesis of ZIKV infection during pregnancy. Our findings are promising for the safety of implementing WNV vaccines in the continental US.
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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：
30.3
作者：
Aguado LC;Schmid S;Sachs D;Shim JV;Lim JK;tenOever BR
通讯作者：
tenOever BR
影响因子：
120.7
作者：
Honein, Margaret A.;Dawson, April L.;Jamieson, Denise J.
通讯作者：
Jamieson, Denise J.
影响因子：
5.4
作者：
Daffis, Stephane;Lazear, Helen M.;Diamond, Michael S.
通讯作者：
Diamond, Michael S.
影响因子：
64.8
作者：
Kostyuchenko, Victor A.;Lim, Elisa X. Y.;Lok, Shee-Mei
通讯作者：
Lok, Shee-Mei