Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA.
Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
Infect Immun. 2019 Sep 19;87(10). doi: 10.1128/IAI.00506-19. Print 2019 Oct.
is an etiologic agent of respiratory diseases in animals and humans. Despite the widespread use of veterinary vaccines, there is limited information on their composition and relative efficacy and on the immune responses that they elicit. Furthermore, human vaccines are not available. We leveraged the dual antigenic and adjuvant functions of colonization factor A (BcfA) to develop acellular vaccines in the absence of an additional adjuvant. BALB/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and the antigens FHA and Prn were equally protected against challenge with a prototype strain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine and provided protection against a strain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection against bordetellae and other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA and Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed BALB/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single-component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines against bordetellae and other pathogens.
是一种动物和人类呼吸道疾病的病原体。尽管兽医疫苗被广泛使用,但关于它们的组成、相对效力以及所引起的免疫反应的信息有限。此外,还没有人类疫苗。我们利用定植因子 A(BcfA)的双重抗原和佐剂功能,在不添加额外佐剂的情况下开发了非细胞疫苗。单独用 BcfA 免疫或用包含 BcfA 和 FHA 及 Prn 抗原的三价疫苗免疫的 BALB/c 小鼠,在原型菌株攻毒时同样得到保护。三价疫苗比犬用疫苗 Bronchicine 更能显著保护小鼠,并能抵抗一种从犬传染性气管支气管炎犬分离的菌株。Th1/17 极化的免疫反应与针对博德特氏菌和其他呼吸道病原体的长期保护相关。值得注意的是,BcfA 强烈减弱了 FHA 和 Prn 引起的 Th2 反应,导致固有 Th2 偏向的 BALB/c 小鼠产生 Th1/17 偏向的反应。因此,BcfA 既是抗原又是佐剂,作为单一成分疫苗提供保护。BcfA 佐剂疫苗可能提高针对博德特氏菌和其他病原体的疫苗的效力和持久性。