Michelle Galeas-Pena, Allyson Hirsch, Erin Kuang, Joseph Hoffmann, Patrick Gellings, Jasmine B Brown, Vanessa M Limbert, Claire L Callahan, James B McLachlan, Lisa A Morici
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引用次数: 0
摘要
百日咳是由革兰氏阴性球菌百日咳杆菌引起的一种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。在这里,我们开发并测试了一种由 aP 抗原和 T-vant(一种从细菌外膜囊泡中提取的新型佐剂)组成的鼻内疫苗,它能引起粘膜和全身免疫反应。我们假设用 aP-T-vant 对小鼠进行免疫可增强粘膜免疫并消灭呼吸道中的百日咳杆菌。与肌肉注射 aP 疫苗的小鼠相比,aP-T-vant 的鼻内免疫可消灭肺部和鼻咽部的细菌。保护作用与肺部和鼻咽部产生 IFN-gamma 和 IL-17 的非循环 CD4 + T 细胞有关,鼻咽部的杀菌免疫依赖于 IL-17。新型粘膜佐剂(如 T-vant)值得进一步研究,以提高下一代百日咳疫苗的功效。
A novel outer membrane vesicle adjuvant improves vaccine protection against Bordetella pertussis.
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.
NPJ VaccinesImmunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍:
Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.