Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.
Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.
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DOI：
10.1371/journal.pntd.0005168
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发表时间：
2016-12
影响因子：
3.8
通讯作者：
O'Connor DH
中科院分区：
文献类型：
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作者：
Aliota MT;Dudley DM;Newman CM;Mohr EL;Gellerup DD;Breitbach ME;Buechler CR;Rasheed MN;Mohns MS;Weiler AM;Barry GL;Weisgrau KL;Eudailey JA;Rakasz EG;Vosler LJ;Post J;Capuano S 3rd;Golos TG;Permar SR;Osorio JE;Friedrich TC;O'Connor SL;O'Connor DH
寨卡病毒（ZIKV；黄病毒科，黄病毒属）在2016年2月被世界卫生组织（WHO）宣布为国际关注的突发公共卫生事件，因为有证据表明寨卡病毒感染与神经系统并发症有关，例如成人中的吉兰 - 巴雷综合征以及发育中的胎儿出现包括小头畸形在内的先天性出生缺陷。由于寨卡病毒疫苗的研发是首要研究重点，并且许多RNA病毒的遗传和抗原变异性限制了疫苗的有效性，所以评估针对一种寨卡病毒株所引发的免疫是否足以对所有寨卡病毒株提供广泛保护至关重要。最近，体外研究表明寨卡病毒可能作为单一血清型传播。在此，我们证明非洲谱系寨卡病毒引发的免疫可保护恒河猴免受亚洲谱系寨卡病毒的后续感染。
利用我们最近开发的恒河猴寨卡病毒感染模型，我们报告称原型寨卡病毒株MR766可有效感染恒河猴，并且由MR766引发的免疫可保护恒河猴免受异源亚洲寨卡病毒的感染。此外，利用新一代深度测序，我们发现该病毒在恒河猴体内复制时一个假定的N - 连接糖基化位点得以恢复，而这个位点在研究界广泛使用的众多MR766毒株中是缺失的。这种回复突显了仔细检查所有病毒株的序列组成以及了解传代历史如何使病毒改变其原始形态的重要性。
需要一种有效的寨卡病毒疫苗来预防与感染相关的胎儿异常。免疫反应由东非寨卡病毒感染引发的恒河猴在随后受到异源亚洲寨卡病毒再次攻击时，完全免受可检测到的病毒血症的影响。因此，这些数据表明免疫原的选择不太可能对疫苗保护的广度产生不利影响，即任何能预防同源攻击的亚洲寨卡病毒免疫原都可能对所有其他亚洲寨卡病毒株提供保护。
寨卡病毒（ZIKV）分离株在基因上具有多样性，但属于两个公认的谱系，称为“非洲”和“亚洲”。孕期感染亚洲寨卡病毒会导致胎儿异常，包括小头畸形。研发一种能保护孕妇的有效预防性寨卡病毒疫苗对于将胎儿异常降至最低至关重要；至少有18个团队正在研发寨卡病毒疫苗。许多RNA病毒的遗传和抗原变异性限制了疫苗的有效性，并且针对一种寨卡病毒株的免疫能在多大程度上对另一种病毒株提供保护尚不清楚。在此我们表明，感染东非寨卡病毒株MR766的恒河猴完全免受后续异源亚洲寨卡病毒的感染。MR766与所有已知亚洲寨卡病毒株在基因上的差异比亚洲寨卡病毒株之间的差异更大。因此，寨卡病毒株的选择不太可能影响疫苗的有效性。
Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains. Zika virus (ZIKV) isolates are genetically diverse, but belong to two recognized lineages, termed “African” and “Asian.” Asian ZIKV infection during pregnancy causes fetal abnormalities including microcephaly. Developing an effective preventative Zika virus vaccine that protects pregnant women is essential for minimizing fetal abnormalities; at least 18 groups are developing ZIKV vaccines. The genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, and the degree to which immunity against one ZIKV strain could provide protection against another is unknown. Here we show that rhesus macaques infected with the East African ZIKV strain MR766 are completely protected from subsequent infection with heterologous Asian ZIKV. MR766 is more genetically divergent from all known Asian ZIKV strains than Asian ZIKV strains are from one another. Therefore, ZIKV strain selection is unlikely to compromise vaccine effectiveness.