Cheng Yahui, Shen Rong, Liu Fanglei, Li Yanting, Wang Jing, Hou Yali, Liu Yueping, Zhou Haifei, Hou Fengping, Wang Yunjin, Li Xiongxiong, Qiao Ruijie, Luo Shuquan
Lanzhou Institute of Biological Products Co., Ltd., Lanzhou 730046, China.
Lanzhou Institute of Biological Products Co., Ltd., Lanzhou 730046, China.
Vaccine. 2024 Apr 19;42(11):2781-2792. doi: 10.1016/j.vaccine.2024.03.039. Epub 2024 Mar 19.
Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.
研究W135脑膜炎球菌结合疫苗(PSW135-TT)在小鼠体内激活适应性免疫反应的机制,有助于全面了解细菌多糖结合疫苗的免疫机制。我们比较了用W135脑膜炎球菌荚膜多糖(PSW135)、破伤风类毒素(TT)和PSW135-TT免疫小鼠后的B细胞和T细胞免疫反应。结果显示,PSW135-TT能诱导产生更高水平的PSW135特异性和TT特异性IgG抗体,两剂接种后有显著增强。所有用PSW135-TT免疫的血清抗体均具有很强的杀菌活性,而用PSW135免疫的血清抗体均无杀菌活性。此外,两剂接种后用PSW135-TT免疫产生的IgM和IgG抗体与杀菌抗体滴度呈正相关。我们还发现,在PSW135-TT、PSW135和TT免疫的小鼠中,Th细胞倾向于Th2型体液免疫反应,尤其是外周血淋巴细胞。此外,PSW135-TT和TT能有效激活小鼠骨髓来源的树突状细胞(BMDCs),并促进BMDCs高表达主要组织相容性复合体Ⅱ(MHCⅡ)、CD86和CD40分子,而PSW135则不能。这些数据证实了PSW135-TT和TT作为T细胞依赖性抗原(TD-Ag)以及PSW135作为T细胞非依赖性抗原(TI-Ag)的典型特征,这将有助于未来进一步探索多糖-蛋白结合疫苗的免疫机制并提高细菌多糖结合疫苗的质量。