Protective effects of in vivo‐expressed autotransporters against Bordetella pertussis infection

Abstract

Bordetella pertussis causes whooping cough, a severe and prolonged respiratory disease that results inhas high morbidity and mortality rates, particularly in developing countries. The number incidence of whooping cough cases is increasing in many countries despite high vaccine coverage. Causes for the re-emergence of the disease include the limited duration of protection conferred by the acellular pertussis vaccines (aP)s and pathogenic adaptations that involve antigenic divergence from vaccine strains. Therefore, current vaccines therefore need to be improved. In the present study, we focused on five autotransporters: namely SphB1, BatB, SphB2, Phg, and Vag8, which were previously found to be expressed by B. bronchiseptica during the course of infection in rats and examined their protective efficiencies as vaccine antigens. The passenger domains of these proteins were produced in recombinant forms and used as antigens. An intranasal murine challenge assay showed that immunization with a mixture of SphB1 and Vag8 (SV) significantly reduced bacterial load in the lower respiratory tract and a combination of aP and SV acts synergistically in effects of conferring protection against B. pertussis infection, implying that these antigens have potential as components to for improvinge th the currently available acellular pertussis vaccine.

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

“…In the current study, we compared intranasal and subcutaneous immunization with omvPV from the B1917 strain (summarized in Table 1). Both subcutaneous and intranasal administration induced a Th1/Th17 polarized www.nature.com/scientificreports www.nature.com/scientificreports/ response and a broad humoral response in terms of multiple subclasses and against several antigens that were proven to be protective, such as BrkA 20,28 , LPS 17 and Vag8 18 . These results indicate that the Th1/Th17 immune profile is related to omvPV, more than to the route of immunization.…”

“…Pertussis outer membrane vesicles (omvPV) are currently developed as a non-replicating vaccine candidate 11 that provides protection against a B. pertussis infection in mice after intraperitoneal 12 and subcutaneous immunization 13 . The protective immune response is characterized by a mixed Th1/2/17 response [13][14][15] and a broad antibody response against multiple antigens such as Bordetella resistance to killing (BrkA), pertactin (Prn), autotransporter Vag8 and lipopolysaccharide (LPS) 16 , which are antigens that were all demonstrated to have protective capacity [17][18][19][20] . However, despite the excellent induction of systemic responses by systemic omvPV immunization, nasal carriage is not diminished.…”

Localization of regions of aBordetella pertussisautotransporter, Vag8, interacting with C1 inhibitor

“…DNA fragments encoding WT and truncated derivatives of Vag8 were amplified from B. pertussis 18323 using appropriate primers (Table S1 in the supplemental material), and cloned into the Xho I- Eco RI or Xho I- Hin dIII sites of pCold II-HAT (3). The expression of each Vag8 derivative from Escherichia coli BL21 (DE3) or DH5α harboring each expression vector was induced with 1 mM isopropyl β-D-1-thiogalactopyranoside.…”

“…Bordetella pertussis causes pertussis (whooping cough), a contagious respiratory disease that has recently seen a resurgence despite high vaccination coverage (1, 2), which has prompted attempts to improve current pertussis vaccines. A number of groups have attempted to identify novel bacterial components that confer efficient immunity against B. pertussis infection, and proposed virulence-associated gene 8 (Vag8) as a possible candidate (3, 4). Vag8 is an autotransporter, which is autonomously secreted by an intramolecular system consisting of passenger and translocator domains.…”

Immunomodulation as a Novel Strategy for Prevention and Treatment of Bordetella spp. Infections

“…After demonstrating via in vitro experiments that the autotransporter BrkA would be a good candidate to generate antibodies that kill Bordetella spp., BrkA has been tested as an adjuvant of the current acellular pertussis vaccine, the results of which revealed robust lung protection against infection with B. pertussis (248,249). Two other autotransporters, Vag8 (250,251) and SphB1, when added to the current pertussis vaccine resulted in improved protection against B. pertussis infection (252). Adenylate cyclase toxin (ACT), when added to a current vaccine formulation significantly decreased inflammation and increased the generation of protective immunity (253,254).…”