Development and characterization of attenuated metabolic mutants of Bordetella bronchiseptica for applications in vaccinology

Abstract

Bordetella bronchiseptica is an important pathogen causing a number of veterinary respiratory syndromes in agriculturally important and food-producing confinement-reared animals, resulting in great economic losses annually amounting to billions of euros worldwide. Currently available live vaccines are incompletely satisfactory in terms of efficacy and safety. An efficient vaccine for livestock animals would allow reducing the application of antibiotics, thereby preventing the massive release of pharmaceuticals into the environment. Here, we describe two new potential vaccine strains based on the BB7865 strain. Two independent attenuating mutations were incorporated by homologous recombination in order to make negligible the risk of recombination and subsequent reversion to the virulent phenotype. The mutations are critical for bacterial metabolism, resistance to oxidative stress, intracellular survival and in vivo persistence. The resulting double mutants BB7865 risA aroA and BB7865 risA dapE were characterized as promising vaccine candidates, which are able to confer protection against colonization of the lower respiratory tract after sublethal challenge with the wild-type strain.

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

“…Bordetella bronchiseptica is a gram-negative respiratory pathogen of several mammalian species, which is causing a number of veterinary respiratory syndromes in domestic as well as agriculturally important and food-producing animals, whilst humans are only rarely infected [ 20 , 21 ]. B. bronchiseptica is genetically closely related to the major human pathogen Bordetella pertussis , the cause of whooping cough.…”

A Marker-Free Bordetella bronchiseptica aroA/bscN Double Deleted Mutant Confers Protection Against Lethal Challenge

“…bronchiseptica vaccines such as the inactivated vaccines and/or the subunit vaccines including the recombinant OMPs or the novel adjuvant BfcA are commercially available or reported in laboratory phase [10,15,16], attenuated live vaccines are still proposed to be the preferable vaccines [17]. First, compared to the inactivated B. bronchiseptica vaccines and/or subunit vaccines which are often administered intramuscularly, the attenuated live B. bronchiseptica vaccines are administered through intranasal inoculation, which represents an easier way for administration [6,[17][18][19]. Second but the most important reason, administration of the attenuated live B. bronchiseptica vaccine is capable of inducing mucosal immune response [6].…”

“…It has been described that the sIgA antibodies play an important role in limiting the overgrowth of commensal microbes, and they also protect the host by binding to the surface of luminal microbes and toxins to prevent them from attaching to epithelial cells [5]. Therefore, the induction of the mucosal immunity and the production of the sIgA antibodies are crucial in order to prevent subsequent bacterial infections [11,17]. It is worthy of note that all of the results obtained from the present study are in agreement with those from the pigs immunized with the aroA deleted B. bronchiseptica QH0814 [6].…”

Immunogenicity of recombinant outer membrane porin protein and protective efficacy against lethal challenge with Bordetella bronchiseptica in rabbits

“…The vaccines being investigated in the laboratory research phase mainly focus on inactivated whole‐cell vaccines and attenuated B. bronchiseptica intranasal or oral vaccines (Stevenson and Roberts ; Yevsa et al . ; Scott‐Garrard et al . ).…”