Bordetella bronchiseptica and Bordetella pertussis: Similarities and Differences in Infection, Immuno-Modulation, and Vaccine Considerations

Abstract

Bordetella pertussis and Bordetella bronchiseptica belong to the genus Bordetella, which comprises 14 other species. B. pertussis is responsible for whooping cough in humans, a severe infection in children and less severe or chronic in adults. These infections are restricted to humans and currently increasing worldwide. B. bronchiseptica is involved in diverse respiratory infections in a wide range of mammals. For instance, the canine infectious respiratory disease complex (CIRDC), characterized by a chronic cough in dogs. At the same time, it is increasingly implicated in human infections, while remaining an important pathogen in the veterinary field. Both Bordetella can evade and modulate host immune responses to support their persistence, although it is more pronounced in B. bronchiseptica infection. The protective immune responses elicited by both pathogens are comparable, while there are important characteristics in the mechanisms that differ. However, B. pertussis pathogenesis is more difficult to decipher in animal models than those of B. bronchiseptica because of its restriction to humans. Nevertheless, the licensed vaccines for each Bordetella are different in terms of formulation, route of administration and immune responses induced, with no known cross-reaction between them. Moreover, the target of the mucosal tissues and the induction of long-lasting cellular and humoral responses are required to control and eliminate Bordetella. In addition, the interaction between both veterinary and human fields are essential for the control of this genus, by preventing the infections in animals and the subsequent zoonotic transmission to humans.

Keywords: Bordetella; Bordetella bronchiseptica; Bordetella pertussis; adjuvants; immunization; infectious disease; mucosal immunity; one health; persistence; vaccines.

FIG 1

Immune response against Bordetella. B. pertussis and B. bronchiseptica target the ciliated epithelial cells of the respiratory tract. Bordetella FHA and FIM mediate the binding to the cilia, and B. pertussis TCT is involved in the loss of cilia and necrosis. LPS/LOS trigger an early inflammatory response characterized by the influx of neutrophils. However, the ability to mount a response against B. pertussis is diminished because of the PT toxin-induced inhibition. Macrophages take up Bordetella and the bacteria are either destroyed by phagocytosis or persist and survive in these cells. Bordetella modulates the innate immune response to induce early IL-10 secretion by APCs to block IFN-γ and promote persistence. This modulation is regulated by B. bronchiseptica T3SS and by B. pertussis LOS. Activated DCs, then induce the differentiation of naive T cells into Th1, Th17, and Treg cells. IL-17 and IFN-γ secreted by Th1 and Th17 cells also contribute to the induction of inflammation at later stages and induce B cell responses and the secretion of opsonizing antibodies. Lipooligosacharide (LOS), Pertussis toxin (PT), Fimbriae (FIM), Tracheal cytotoxin (TCT), Type III Secretory System (T3SS), Lipopolysaccharide (LPS), Adenylate Cyclase toxin (ACT), and Antigen-presenting cells (APCs).

FIG 2

Main antigens of B. pertussis and B. bronchiseptica and their roles in infection, immunity, and vaccines. All the indicated antigens play a key role in the adhesion, pathogenesis, and immunomodulation of the disease and at the same time elicit immune responses of interest for current and future vaccine formulations. Pertactin (PRN), Lipooligosacharide (LOS), Pertussis toxin (PTX), Fimbriae (FIM), Filamentous Hemagglutinin (FHA), Type III Secretory System (T3SS), Lipopolysaccharide (LPS), and Adenylate Cyclase toxin (ACT).

FIG 3

Present and future vaccines against Bordetella. Bordetella pertussis licensed vaccines are either whole-cell inactivated or acellular adjuvanted and are administered parenterally. On the other hand, B. bronchiseptica vaccines consist of live attenuated, whole-cell, and antigen extracts administered either parenterally, orally, or nasally. Proposals for novel modifications are listed, starting from modification of whole-cell pertussis vaccines, followed by the choice of the right antigen and adjuvant to obtain protective immune responses, as well as the route of administration to stop the transmission. Finally, novel platforms, such as live attenuated vaccines and OMV for B. pertussis and B. bronchiseptica, are proposed. LP-GMP (Combination of TLR2 and STING agonists), E515 (vegetable oil adjuvant), TPPPS (Taishan Pinus massoniana pollen polysaccharides), CpG (cytosine phosphoguanine), ACT (Adenylate cyclase toxin), and TQ1055 (saponin-based adjuvant).

FIG 4

Strategies to effectively control Bordetella species in humans. The new generation of vaccines should contain immunogenic and conserved antigens, along with adjuvants that elicit cellular responses, and they should be administered by the mucosal route. Moreover, persistence mechanisms, correlates of protection, and genomic evolution need to be further studied and monitored. It is crucial to perform epidemiological surveillance of Bordetella cases, other than B. pertussis, as well as macrolide-resistant B. pertussis. Finally, Bordetella should also be controlled in animal species, as they are the main source of transmission to humans.