为了开始优化我们报道的PLGA-rMOMP纳米疫苗[PLGA包裹的衣原体(Cm)重组主要外膜蛋白(rMOMP)]的免疫途径,我们比较了两种初免-加强免疫策略(皮下(SC)和肌内(IM-p)初免途径,随后进行两次SC加强免疫),以评估纳米疫苗在雌性BALB/c小鼠中诱导的保护功效和免疫原性.我们的结果表明,通过SC和IM-p途径免疫的小鼠通过减少细菌负担和SC小鼠中的细菌减少而免受Cm生殖器攻击。与rMOMP特异性Th1(IL-2,IFN-γ)而不是Th2(IL-4,IL-9,IL-13)细胞因子相关的小鼠的保护,和CD4+记忆(CD44highCD62Lhigh)T细胞,特别是在SC小鼠中。我们还观察到更高水平的IL-1α,SC免疫小鼠中的IL-6、IL-17、CCL-2和G-CSF。值得注意的是,在SC中的攻击后观察到细胞因子/趋化因子的增加,IM-p,和对照小鼠(rMOMP和PBS),暗示厘米刺激。并行,rMOMP特异性Th1(IgG2a,IgG2b)和Th2(IgG1)血清,粘膜,血清亲和力,和中和抗体在SC比IM-p小鼠中升高。总的来说,与异源IM-p相比,小鼠的同源SC初免-加强免疫诱导增强的细胞和抗体应答,具有更好的针对生殖器攻击的保护作用。
To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p.