Porier Danielle L, Adam Awadalkareem, Kang Lin, Michalak Pawel, Tupik Juselyn, Santos Matthew A, Lee Christy, Allen Irving C, Wang Tian, Auguste Albert J
bioRxiv. 2023 Mar 1:2023.03.01.530296. doi: 10.1101/2023.03.01.530296.
Vaccination is critical for the control and prevention of viral outbreaks, yet conventional vaccine platforms may involve trade-offs between immunogenicity and safety. Insect-specific viruses have emerged as a novel vaccine platform to overcome this challenge. Detailed studies of humoral and T-cell responses induced by new insect-specific flavivirus (ISFV)-based vaccine platforms are needed to better understand correlates of protection and improve vaccine efficacy. Previously, we used a novel ISFV called Aripo virus (ARPV) to create a Zika virus (ZIKV) vaccine candidate (designated ARPV/ZIKV). ARPV/ZIKV demonstrated exceptional safety and single-dose efficacy, completely protecting mice from a lethal ZIKV challenge. Here, we explore the development of immune responses induced by ARPV/ZIKV immunization and evaluate its correlates of protection. Passive transfer of ARPV/ZIKV-induced immune sera to naïve mice prior to challenge emphasized the importance of neutralizing antibodies as a correlate of protection. Depletion of T-cells in vaccinated mice and adoptive transfer of ARPV/ZIKV-primed T-cells to naïve mice prior to challenge indicated that ARPV/ZIKV-induced CD4 and CD8 T-cell responses contribute to the observed protection but may not be essential for protection during ZIKV challenge. However, vaccination of Rag1 KO, Tcra KO, and muMt mice demonstrated the critical role for ARPV/ZIKV-induced T-cells in developing protective immune responses following vaccination. Overall, both humoral and T-cell-mediated responses induced by ISFV-based vaccines are important for comprehensive immunity, and ISFV platforms continue to be a promising method for future vaccine development.
疫苗接种对于控制和预防病毒爆发至关重要，但传统疫苗平台可能在免疫原性和安全性之间存在权衡。昆虫特异性病毒已成为克服这一挑战的新型疫苗平台。需要对基于新型昆虫特异性黄病毒（ISFV）的疫苗平台诱导的体液和T细胞反应进行详细研究，以更好地理解保护的相关因素并提高疫苗效力。此前，我们使用一种名为阿里波病毒（ARPV）的新型ISFV创建了一种寨卡病毒（ZIKV）候选疫苗（命名为ARPV/ZIKV）。ARPV/ZIKV表现出卓越的安全性和单剂量效力，能完全保护小鼠免受致命的ZIKV攻击。在此，我们探讨ARPV/ZIKV免疫诱导的免疫反应的发展，并评估其保护的相关因素。在攻击前将ARPV/ZIKV诱导的免疫血清被动转移至未免疫小鼠，突出了中和抗体作为保护相关因素的重要性。在接种疫苗的小鼠中耗尽T细胞，并在攻击前将经ARPV/ZIKV致敏的T细胞过继转移至未免疫小鼠，表明ARPV/ZIKV诱导的CD4和CD8 T细胞反应有助于观察到的保护作用，但在ZIKV攻击期间可能对保护并非必不可少。然而，对Rag1基因敲除、Tcra基因敲除和μMt小鼠进行疫苗接种，证明了ARPV/ZIKV诱导的T细胞在疫苗接种后产生保护性免疫反应中的关键作用。总体而言，基于ISFV的疫苗诱导的体液和T细胞介导的反应对于全面免疫都很重要，并且ISFV平台仍然是未来疫苗开发的一种有前景的方法。
