Bordetella Colonization Factor A (BcfA) elicits protective immunity againstBordetella bronchisepticain the absence of an additional adjuvant

Abstract

15 Bordetella bronchiseptica (B. bronchiseptica) is an etiologic agent of respiratory 16 diseases in animals and humans. Despite widespread use of veterinary B. 17 bronchiseptica vaccines, there is limited information on their composition, relative 18 efficacy, and the immune responses they elicit. Furthermore, human B. bronchiseptica 19 vaccines are not available. We leveraged the dual antigenic and adjuvant functions of 20 BcfA to develop acellular B. bronchiseptica vaccines in the absence of an additional 21 adjuvant. Balb/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA 22 and the Bordetella antigens FHA and Prn were equally protected against challenge with 23 a prototype B. bronchiseptica strain. The trivalent vaccine protected mice significantly 24 better than the canine vaccine Bronchicine ® and provided protection against a B. 25 bronchiseptica strain isolated from a dog with kennel cough. Th1/17-polarized immune 26 responses correlate with long-lasting protection against Bordetellae and other 27 respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by 28 FHA/Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed Balb/c mice. 29 Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a 30 single component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and 31 durability of vaccines against Bordetellae and other pathogens.32 33 34Bordetella bronchiseptica (B. bronchiseptica) is an animal pathogen with a wide 35 host range, infecting farm and companion animals(1-6). It is one of the etiologic agents 36 of kennel cough, or canine infectious respiratory disease (CIRD)(7). B. bronchiseptica is 37 also increasingly isolated from immunocompromised humans such as those with 38 HIV/AIDS, cancer, or cystic fibrosis. In many of these cases, the infections are linked to 39 exposure to pets with B. bronchiseptica (8)(9)(10). 40 A nasal live attenuated (11) and a parenteral cellular antigen extract (CAe) 41 vaccine (Bronchicine)(12) against B. bronchiseptica are widely used to minimize kennel 42 cough outbreaks. The CAe formulation replaced more reactogenic whole cell inactivated 43 vaccines in parallel to the development of acellular pertussis vaccines (aPV). However, 44 a human vaccine against B. bronchiseptica is not available. Although antigens 45 expressed by B. bronchiseptica are present in aPV against the human pathogen, B. 46 pertussis(13, 14), these vaccines are only partially effective against B. 47 bronchiseptica(15). 48 While considerable efforts have been devoted to evaluation of the immune 49 response and effectiveness of aPV, there is insufficient research to determine the 50 effectiveness of CAe B. bronchiseptica vaccines. Dogs vaccinated with CAe produced 51 serum IgG and IgA and had reduced bacterial burden compared to unvaccinated 52 dogs(16, 17). However, minor vaccine-related side effects were observed and coughing 53 in 20% of immunized animals was reported, suggesting that the vaccine does not ...

Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces B. pertussis nasal colonization

“…It is a pseudogene in the human pathogen B. pertussis ( 29 ). We showed that BcfA is an adjuvant that elicits Th1/17 polarized T cell and antibody responses to a variety of protein antigens ( 30 , 31 ). Additionally, when combined with alum, BcfA attenuated alum primed Th2 responses.…”