Abstract

The Bordetella species are Gram-negative bacterial pathogens that colonizes mammalian respiratory tract causing respiratory diseases in humans and animals. B. bronchiseptica causes clinical conditions in many mammals including immunocompromised humans. Using the dog model of respiratory infection, it has been shown in this study that a newly developed B. bronchiseptica Bacterial Ghost (BbBG) vaccine exhibited significant protection in the face of a severe pathogenic bacterial challenge in seronegative dogs. The protein E-specific lysis mechanism was used to produce BbBGs. Bacterial Ghosts (BGs) are the empty cell envelope of Gram-negative bacterium. They are genetically processed to form a microscopic hole in their membrane, through which all the cytoplasmic contents are expelled leaving behind intact empty bacterial shells. Due to the intact surface structures of BGs, they offer the safety of inactivated but efficacy of live attenuated vaccines. In this study, seronegative dogs were vaccinated subcutaneously (s/c) with two different doses of a newly developed BbBG vaccine [lower 10∧5 (BbBG – 5) and higher 10∧7 (BbBG – 7)] on day 0 and 21. The animals were challenged (by aerosol) with virulent live B. bronchiseptica strains 41 days after first vaccination. The dogs vaccinated s/c with BbBG – 7 vaccine had significantly lower spontaneous coughing scores (P = 0.0001) than dogs in negative control group. Furthermore, the tested BbBG – 7 vaccine was equivalent to the positive control vaccine Bronchicine CAe in terms of safety and efficacy. For the first time, we report the successful use of liquid formulated BGs vaccines in animal studies. Earlier reported studies using BGs vaccines were performed with resuspended freeze-dried BGs preparations.

Highlights

  • The Bordetella bronchiseptica is gram-negative aerobic coccobacillus and is widely known for causing canine infectious respiratory disease (CIRD) known as kennel cough

  • We evaluated the protection conferred by an injectable vaccine which is a cell antigen extract of B. bronchiseptica vs. a more defined envelope of B. bronchiseptica produced using propriety Bacterial Ghost platform technology

  • Transformed B. bronchiseptica 110H was grown with aeration in a total volume of 4 L, and the OD and live cell counts were monitored during the growth and lysis phase

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Summary

Introduction

The Bordetella bronchiseptica is gram-negative aerobic coccobacillus and is widely known for causing canine infectious respiratory disease (CIRD) known as kennel cough. The canine respiratory cilia lose their beating motion within 3 h of a phase I or an intermediate phase B. bronchiseptica infection where almost 100% of ciliary activity is lost [23]. Due to this ciliostasis, the respiratory epithelia of dogs are more prone to secondary viral and bacterial infections [22,23,24]

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