Richardson Shakyra, Medhavi F N U, Tanner Tayhlor, Lundy Stephanie, Omosun Yusuf, Igietseme Joseph U, Eko Francis O
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA; National Center for Emerging Zoonotic and Infectious Diseases, Center for Disease Control and Prevention (CDC), Atlanta, GA, USA.
Microbes Infect. 2025 Mar-Apr;27(3):105463. doi: 10.1016/j.micinf.2024.105463. Epub 2024 Dec 5.
We investigated if the efficacy of a Chlamydia abortus (Cab) subunit vaccine is influenced by route of administration. Thus, female CBA/J mice were immunized either by mucosal or systemic routes with Vibrio cholerae ghost (VCG)-based vaccine expressing T and B cell epitopes of Cab polymorphic membrane protein (Pmp) 18D, termed rVCG-Pmp18.3. Vaccine evaluation revealed that all routes of vaccine delivery induced a Th1-type antibody response after a prime boost or three-dose immunization regimen. Also, the intranasal and rectal mucosal and intramuscular systemic routes induced cross-reactive neutralizing antibodies against homologous and heterologous Cab strains. Irrespective of the route of immunization, the vaccine elicited a Th1-type cytokine response (IFN-γ/IL-4 >1) in immunized mice. Analysis of reduction in genital Cab burden as an index of protection showed that immunization induced substantial degrees of protection against infection, irrespective of route of delivery with the intranasal and rectal mucosal routes showing superior levels of protection 12 days postchallenge. Furthermore, there was correlation between the humoral and cellular immune response and protection was associated with the Cab-specific serum IgG antibody avidity and IFN-γ. Thus, while route of administration impacts vaccine efficacy, the rVCG-Pmp18.3-induced protective immunity against Cab respiratory infection can be accomplished by both mucosal and systemic immunization.
我们研究了流产衣原体(Cab)亚单位疫苗的效力是否受给药途径的影响。因此,用表达Cab多形膜蛋白(Pmp)18D的T和B细胞表位的基于霍乱弧菌空壳(VCG)的疫苗,即rVCG-Pmp18.3,通过粘膜或全身途径免疫雌性CBA/J小鼠。疫苗评估显示,在初次加强或三剂免疫方案后,所有疫苗递送途径均诱导了Th1型抗体反应。此外,鼻内和直肠粘膜以及肌肉内全身途径诱导了针对同源和异源Cab菌株的交叉反应性中和抗体。无论免疫途径如何,该疫苗在免疫小鼠中均引发了Th1型细胞因子反应(IFN-γ/IL-4>1)。以生殖道Cab负荷降低作为保护指标的分析表明,免疫诱导了对感染的高度保护,无论给药途径如何,鼻内和直肠粘膜途径在攻毒后12天显示出更高的保护水平。此外,体液和细胞免疫反应之间存在相关性,保护与Cab特异性血清IgG抗体亲和力和IFN-γ相关。因此,虽然给药途径会影响疫苗效力,但rVCG-Pmp18.3诱导的针对Cab呼吸道感染的保护性免疫可通过粘膜和全身免疫实现。