Tada Rui, Honjo Emi, Muto Shoko, Takayama Noriko, Kiyono Hiroshi, Kunisawa Jun, Negishi Yoichi
Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Membranes (Basel). 2022 Jun 20;12(6):635. doi: 10.3390/membranes12060635.
An advantage of mucosal vaccines over conventional parenteral vaccines is that they can induce protective immune responses not only at mucosal surfaces but also in systemic compartments. Despite this advantage, few live attenuated or inactivated mucosal vaccines have been developed and applied clinically. We recently showed that the intranasal immunization of ovalbumin (OVA) with class B synthetic oligodeoxynucleotides (ODNs) containing immunostimulatory CpG motif (CpG ODN)-loaded cationic liposomes synergistically exerted both antigen-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) responses in mice. However, the mechanism underlying the mucosal adjuvant activity of CpG ODN-loaded liposomes remains unknown. In the present study, we showed that the intranasal administration of CpG ODN-loaded cationic liposomes elicited interleukin (IL)-6 release in nasal tissues. Additionally, pre-treatment with an anti-IL-6 receptor (IL-6R) antibody attenuated antigen-specific nasal IgA production but not serum IgG responses. Furthermore, the intranasal administration of OVA and CpG ODN-loaded cationic liposomes increased the number of IgA/CD138 plasma cells and IgA/B220 B cells in the nasal passages. This increase was markedly suppressed by pre-treatment with anti-IL-6R blocking antibody. In conclusion, IL-6 released by CpG ODN-loaded cationic liposomes at the site of administration may play a role in the induction of antigen-specific IgA responses by promoting differentiation into IgA plasma cells for IgA secretion from B cells.
黏膜疫苗相对于传统的肠胃外疫苗的一个优势在于，它们不仅能在黏膜表面诱导保护性免疫反应，还能在全身各部位诱导此类反应。尽管有这一优势，但很少有减毒活疫苗或灭活黏膜疫苗得到研发并应用于临床。我们最近发现，用含有免疫刺激CpG基序（CpG ODN）的B类合成寡脱氧核苷酸（ODN）负载的阳离子脂质体经鼻免疫卵清蛋白（OVA），可在小鼠体内协同引发抗原特异性黏膜免疫球蛋白A（IgA）和全身免疫球蛋白G（IgG）反应。然而，负载CpG ODN的脂质体的黏膜佐剂活性背后的机制仍不清楚。在本研究中，我们发现经鼻给予负载CpG ODN的阳离子脂质体可在鼻组织中引发白细胞介素（IL）-6释放。此外，用抗IL-6受体（IL-6R）抗体进行预处理可减弱抗原特异性鼻IgA的产生，但不影响血清IgG反应。此外，经鼻给予OVA和负载CpG ODN的阳离子脂质体可增加鼻道中IgA/CD138浆细胞和IgA/B220 B细胞的数量。用抗IL-6R阻断抗体进行预处理可显著抑制这种增加。总之，负载CpG ODN的阳离子脂质体在给药部位释放的IL-6可能通过促进B细胞分化为IgA浆细胞以分泌IgA，从而在诱导抗原特异性IgA反应中发挥作用。
