Galeas-Pena Michelle, Hirsch Allyson, Kuang Erin, Hoffmann Joseph, Gellings Patrick, Brown Jasmine B, Limbert Vanessa M, Callahan Claire L, McLachlan James B, Morici Lisa A
Tulane University School of Medicine, Dept. of Microbiology and Immunology, New Orleans, LA, 70112, USA.
NPJ Vaccines. 2024 Oct 16;9(1):190. doi: 10.1038/s41541-024-00990-1.
Pertussis is a vaccine-preventable respiratory disease caused by the Gram negative coccobacillus Bordetella pertussis. The licensed acellular pertussis (aP) vaccines protect against disease but do not prevent bacterial colonization and transmission. Here, we developed and tested an intranasal vaccine composed of aP antigens combined with T-vant, a novel adjuvant derived from bacterial outer membrane vesicles, that elicits both mucosal and systemic immune responses. We hypothesized that immunization of mice with aP-T-vant would enhance mucosal immunity and eliminate B. pertussis in the respiratory tract. In contrast to mice immunized intramuscularly with the licensed aP vaccine, intranasal immunization with aP-T-vant eliminated bacteria in both the lung and nasopharynx. Protection was associated with IFN-gamma and IL-17-producing, non-circulating CD4 + T cells in the lung and nasopharynx, and sterilizing immunity in the nasopharynx was dependent on IL-17. Novel mucosal adjuvants, such as T-vant, warrant further investigation to enhance the efficacy of next generation pertussis vaccines.
百日咳是一种由革兰氏阴性球杆菌百日咳博德特氏菌引起的可通过疫苗预防的呼吸道疾病。已获许可的无细胞百日咳(aP)疫苗可预防疾病,但不能防止细菌定植和传播。在此,我们研发并测试了一种鼻内疫苗,该疫苗由aP抗原与T-vant(一种源自细菌外膜囊泡的新型佐剂)组成,可引发黏膜和全身免疫反应。我们假设用aP-T-vant免疫小鼠会增强黏膜免疫力并消除呼吸道中的百日咳博德特氏菌。与用已获许可的aP疫苗进行肌肉注射免疫的小鼠不同,用aP-T-vant进行鼻内免疫可消除肺部和鼻咽部的细菌。这种保护作用与肺部和鼻咽部产生干扰素-γ和白细胞介素-17的非循环CD4 + T细胞有关,并且鼻咽部的杀菌免疫依赖于白细胞介素-17。新型黏膜佐剂,如T-vant,值得进一步研究以提高下一代百日咳疫苗的效力。