Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate.
Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate.
复制标题
DOI：
10.1038/s41598-023-47086-9
复制
发表时间：
2023-11-15
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
寨卡病毒（ZIKV）是一种重要的重新出现的黄病毒，对全世界人类健康构成重大威胁。尽管疫苗很重要，但尚未批准用于人类。昆虫特异性黄病毒（ISFV）最近作为疫苗开发和诊断应用的抗原呈递平台而受到关注。在这里，我们进一步探讨了嵌合 ISFV-Zika 候选疫苗（称为 Aripo-Zika (ARPV/ZIKV)）的安全性、免疫原性和有效性。我们的结果显示增加的剂量和免疫原性之间存在近乎线性的关系，1011 个基因组拷贝（即 108 个病灶形成单位）是保护小鼠免受 ZIKV 诱导的发病和死亡所需的最小剂量。包含加强疫苗并没有显着提高 ARPV/ZIKV 疫苗接种小鼠的短期疗效。我们还表明，来自接种 ARPV/ZIKV 的母鼠的断奶小鼠在受到攻击时完全免受 ZIKV 诱导的发病率和死亡率的影响，这表明母源性保护性抗体的有效转移。最后，ZIKV 与 Aripo 病毒 (ARPV) 和 ARPV/ZIKV 在非洲绿猴肾细胞（即 Vero-76）中的体外共感染研究表明，尽管存在活跃的 ZIKV 复制，但 ARPV 和 ARPV/ZIKV 仍然无法在脊椎动物细胞中复制。总而言之，我们的数据继续支持基于 ISFV 的疫苗，特别是 ARPV 骨干是一种安全、免疫原性和有效的黄病毒疫苗策略。
Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platform for vaccine development and diagnostic applications. Here, we further explore the safety, immunogenicity, and efficacy of a chimeric ISFV-Zika vaccine candidate, designated Aripo-Zika (ARPV/ZIKV). Our results show a near-linear relationship between increased dose and immunogenicity, with 1011 genome copies (i.e., 108 focus forming units) being the minimum dose required for protection from ZIKV-induced morbidity and mortality in mice. Including boosters did not significantly increase the short-term efficacy of ARPV/ZIKV-vaccinated mice. We also show that weanling mice derived from ARPV/ZIKV-vaccinated dams were completely protected from ZIKV-induced morbidity and mortality upon challenge, suggesting efficient transfer of maternally-derived protective antibodies. Finally, in vitro coinfection studies of ZIKV with Aripo virus (ARPV) and ARPV/ZIKV in African green monkey kidney cells (i.e., Vero-76) showed that ARPV and ARPV/ZIKV remain incapable of replication in vertebrate cells, despite the presence of active ZIKV replication. Altogether, our data continue to support ISFV-based vaccines, and specifically the ARPV backbone is a safe, immunogenic and effective vaccine strategy for flaviviruses.
登录
查看更多内容
影响因子：
7.8
作者：
Hazlewood JE;Rawle DJ;Tang B;Yan K;Vet LJ;Nakayama E;Hobson-Peters J;Hall RA;Suhrbier A
通讯作者：
Suhrbier A
影响因子：
56.3
作者：
Han, Htay-Htay;Diaz, Clemente;Borkowski, Astrid
通讯作者：
Borkowski, Astrid
影响因子：
168.9
作者：
Franca, Giovanny V. A.;Schuler-Faccini, Lavinia;Victora, Cesar G.
通讯作者：
Victora, Cesar G.
影响因子：
7.8
作者：
Carvalho VL;Long MT
通讯作者：
Long MT
影响因子：
3.2
作者：
Ergunay, Koray;Litzba, Nadine;Linton, Yvonne-Marie
通讯作者：
Linton, Yvonne-Marie