Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV.
Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV.
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DOI：
10.3390/vaccines9111236
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发表时间：
2021-10-23
期刊：
影响因子：
7.8
通讯作者：
Yao Q
中科院分区：
文献类型：
--
作者：
Liu D;Zhang S;Poteet E;Marin-Muller C;Chen C;Yao Q
为了有效预防通过性传播的艾滋病毒，需要开发一种能够在粘膜区室中引发强烈的艾滋病毒特异性抗体反应的疫苗。然而，目前的粘膜疫苗要么口服给药时免疫原性差，要么鼻内给药时引起安全问题。近年来，舌下免疫因其在粘膜和粘膜外组织中诱导全身和粘膜免疫反应的效率而受到更多关注。为了促进免疫原穿过粘膜下上皮屏障的转运，我们发现C1q的受体CD91在舌下粘膜内层普遍表达，因此，产生了修饰的嵌合C1q表面缀合的CD40L/HIV VLP。本研究评估了这种嵌合 C1q/CD40L/HIV VLP 结合、穿过上皮层、进入并激活粘膜下层树突状细胞 (DC) 并最终诱导增强的针对 HIV 的粘膜和全身免疫反应的能力。我们发现，与单独的 CD40L/HIV VLP 相比，C1q/CD40L/HIV VLP 具有增强的结合、增加的跨上皮层转运以及上调 DC 激活标记物。通过舌下给药用 C1q/CD40L/HIV VLP 免疫的小鼠表现出比用 CD40L/HIV VLP 免疫的小鼠更高水平的针对 HIV Gag 和 Env 的 IgA 唾液抗体。此外，与 CD40L/HIV VLP 组相比，舌下免疫 C1q/CD40L/HIV VLP 诱导了更多的 Env 和 Gag 特异性 IFN-γ 产生 T 细胞。有趣的是，C1q/CD40L/HIV VLP免疫也能比CD40L/HIV VLP组诱导更多的粘膜归巢T细胞。我们的数据表明，将 C1q 掺入 CD40L/HIV VLP 是一种有前途的新策略，并且舌下免疫可能是 HIV 粘膜疫苗最喜欢的免疫途径。
Development of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns when administered intranasally. Sublingual immunization has received more attention in recent years based on its efficiency in inducing systemic and mucosal immune responses in both mucosal and extra-mucosal tissues. To facilitate the transport of the immunogen across the sub-mucosal epithelial barrier, we found that CD91, the receptor of C1q, is prevalently expressed in the sublingual mucosal lining, and thus, a modified chimeric C1q surface conjugated CD40L/HIV VLP was generated. The ability of this chimeric C1q/CD40L/HIV VLP to bind, cross the epithelial layer, access and activate the sub-mucosal layer dendritic cells (DCs), and ultimately induce enhanced mucosal and systemic immune responses against HIV is evaluated in this study. We found that C1q/CD40L/HIV VLPs have enhanced binding, increased transport across the epithelial layer, and upregulate DC activation markers as compared to CD40L/HIV VLPs alone. Mice immunized with C1q/CD40L/HIV VLPs by sublingual administration showed higher levels of IgA salivary antibodies against both HIV Gag and Env than mice immunized with CD40L/HIV VLPs. Moreover, sublingual immunization with C1q/CD40L/HIV VLPs induced more Env- and Gag-specific IFN-γ producing T cells than the CD40L/HIV VLPs group. Interestingly, C1q/CD40L/HIV VLP immunization can also induce more mucosal homing T cells than that in CD40L/HIV VLP group. Our data suggest that incorporation of C1q to CD40L/HIV VLPs is a promising novel strategy and that the sublingual immunization can be a favorite immunization route for HIV mucosal vaccines.
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影响因子：
12.8
作者：
Bourazopoulou, Efi;Kapsogeorgou, Efstathia K.;Tzioufas, Athanasios G.
通讯作者：
Tzioufas, Athanasios G.
粘膜疫苗：策略与挑战
影响因子：
4.4
作者：
Li, Miao;Wang, Yi;Qiu, Hua-Ji
通讯作者：
Qiu, Hua-Ji
影响因子：
7.8
作者：
Ma DY;Clark EA
通讯作者：
Clark EA
影响因子：
8
作者：
Hervouet, C.;Luci, C.;Anjuere, F.
通讯作者：
Anjuere, F.
影响因子：
5.4
作者：
Duus, Karen;Hansen, Erik W.;Houen, Gunnar
通讯作者：
Houen, Gunnar