Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells
Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells
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DOI：
10.1016/j.vaccine.2018.01.056
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发表时间：
2018-02-28
期刊：
影响因子：
5.5
通讯作者：
Tumban, Ebenezer
中科院分区：
文献类型：
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作者：
Basu, Rupsa;Zhai, Lukai;Tumban, Ebenezer
寨卡病毒（ZIKV）是一种蚊媒黄病毒，已重新出现，并与许多使人衰弱的临床表现有关。目前正在进行研究以开发针对该病毒的预防性疫苗;然而，还没有任何许可的ZIKV疫苗。最近的研究已经鉴定了ZIKV的包膜蛋白上的潜在B细胞表位（氨基酸241-259、294-315、317-327、346-361、377-388和421-437），其可以被探索以开发针对ZIKV感染的肽疫苗。然而，这些表位的免疫原性从未被评估过。在这里，我们在高免疫原性噬菌体病毒样颗粒（VLP; MS 2，PP 7和Q β）平台上展示了这些表位，并评估了它们在小鼠中的免疫原性。用展示ZIKV包膜B细胞表位的VLP的混合物免疫的小鼠引发抗ZIKV抗体。尽管免疫的小鼠未被保护免于高攻击剂量的ZIKV，但来自免疫的小鼠的血清（尽管是低滴度）中和（体外）低剂量的ZIKV。总之，这些结果表明，这些表位是B细胞表位，并且当展示在Q β VLP平台上时，它们是免疫原性的。此外，结果还显示，用展示单个B细胞表位的VLP免疫最低限度地减少ZIKV感染，而用展示B细胞表位的组合的VLP的混合物免疫中和ZIKV感染。因此，用展示多个ZIKV B细胞表位的VLP的混合物免疫是增强ZIKV中和的良好策略。由爱思唯尔有限公司发布
Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241-259, 294-315, 317-327, 346-361, 377-388 and 421-437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection. Nevertheless, the immunogenicity of these epitopes has never been assessed. Here, we displayed these epitopes on highly immunogenic bacteriophage virus-like particles (VLPs; MS2, PP7 and Q beta) platforms and assessed their immunogenicity in mice. Mice immunized with a mixture of VLPs displaying ZIKV envelope B-cell epitopes elicited anti-ZIKV antibodies. Although, immunized mice were not protected against a high challenge dose of ZIKV, sera- albeit at low titers-from immunized mice neutralized (in vitro) a low dose of ZIKV. Taken together, these results show that these epitopes are B-cell epitopes and they are immunogenic when displayed on a Q beta VLP platform. Furthermore, the results also show that immunization with VLPs displaying a single B-cell epitope minimally reduces ZIKV infection whereas immunization with a mixture of VLPs displaying a combination of the B-cell epitopes neutralizes ZIKV infection. Thus, immunization with a mixture of VLPs displaying multiple ZIKV B-cell epitopes is a good strategy to enhance ZIKV neutralization. Published by Elsevier Ltd.