Yoon Keon-Woong, Chu Ki-Back, Kang Hae-Ji, Kim Min-Ju, Eom Gi-Deok, Quan Fu-Shi
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Korea.
Vaccines (Basel). 2022 Jan 20;10(2):152. doi: 10.3390/vaccines10020152.
Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the rhoptry protein 4 (ROP4) of were generated. To evaluate the protection induced by the vaccines, mice were orally immunized with the ROP4-rVVs and subsequently challenge-infected with a lethal dose of ME49 strain. Immunization with the rVVs induced higher levels of parasite-specific IgG and IgA antibody responses in sera compared to unimmunized control (NC). Upon challenge infection, significantly higher levels of IgG or IgA antibody responses in the brain, intestines, and vaginal samples were found in the immunized mice compared to NC. The ROP4-rVV vaccination elicited potent IgG and IgA secreting cell (ASC) responses, while substantially enhancing germinal center B cell, as well as CD4 and CD8 T cell responses from lymphoid organs. The production of pro-inflammatory cytokines IFN-γ and IL-6 in the brains was markedly diminished following immunization. The immunized mice also experienced reduced bodyweight loss and possessed fewer brain cysts than the control group. These results suggest that oral delivery of ROP4 displaying rVVs induced mucosal and systemic immunities that contributed to protection against lethal challenge infection.
重组痘苗病毒（rVVs）是减毒病毒，被广泛用作针对多种疾病的载体疫苗平台。然而，这些rVV疫苗的保护效力及其所产生的黏膜免疫尚未得到充分评估。在此，构建了表达 虫体棒状体蛋白4（ROP4）的rVVs。为了评估疫苗诱导的保护作用，用ROP4-rVVs对小鼠进行口服免疫，随后用致死剂量的 虫ME49株进行攻击感染。与未免疫对照（NC）相比，用rVVs免疫诱导血清中更高水平的寄生虫特异性IgG和IgA抗体反应。在攻击感染后，与NC相比，在免疫小鼠的脑、肠道和阴道样本中发现显著更高水平的IgG或IgA抗体反应。ROP4-rVV疫苗接种引发了有效的IgG和IgA分泌细胞（ASC）反应，同时显著增强了生发中心B细胞以及来自淋巴器官的CD4和CD8 T细胞反应。免疫后脑内促炎细胞因子IFN-γ和IL-6的产生明显减少。免疫小鼠的体重减轻也比对照组减少，脑囊肿数量也更少。这些结果表明，口服递送展示ROP4的rVVs诱导了黏膜和全身免疫，有助于抵抗致死性 虫攻击感染。
