Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity
Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity
复制标题
14 型和 55 型腺病毒的六邻体和纤维是中和抗体的主要靶标，但只有纤维特异性抗体有助于交叉中和活性。
DOI：
10.1016/j.virol.2018.03.002
复制
发表时间：
2018-05-01
期刊：
影响因子：
3.7
通讯作者：
Feng, Liqiang
中科院分区：
文献类型：
--
作者：
Feng, Ying;Sun, Xikui;Feng, Liqiang
重新出现的人腺病毒14型（HAdV14）和55型（HAdV55）代表两种高毒性腺病毒。由感染或免疫引起的中和抗体（nAb）应答在很大程度上仍然未知。在此，我们产生了六邻体嵌合HAdV14病毒，其具有来自HAdV55的每个单个或整个六邻体高变区（HVR），并确定了人和小鼠nAb的中和表位。在人血清中，六邻体靶向nAb是类型特异性的，主要识别HVR2、5和7。靶向纤维的nAb仅在交叉中和HAdV14和HAdV55的血清中可检测到，并且基本上有助于交叉中和。然而，五邻体结合抗体没有显示出显著的中和活性。在用HAdV14或HAdV55免疫的小鼠中，单次免疫主要引发六邻体特异性nAb，其分别识别HAdV14 HVR1、2和7以及HAdV55 HVR1和2。加强免疫后，交叉中和纤维特异性nAb变得可检测。这些结果表明，六邻体eliminating类型特异性nAb，而纤维诱导交叉中和nAb HAdV14和HAdV55，这在疫苗开发中具有重要意义。
Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development.