Reverse Vaccinology Approach for a Potential Rhinovirus Vaccine

Background: Rhinoviruses (RVs) represent the most important aetiological agents of the common cold and are responsible for about two-thirds of acute exacerbations of chronic bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) in both children and adults. This study aimed to design a pan-serotypic vaccine capable of inducing cross-reactive antibodies against most of the RV by using a reverse Vaccinology approach. Methods: Bioinformatics analysis was carried out to characterise the capsid proteins (VP1, VP2, VP3, and VP4) of all known RV serotypes and to predict potential immune motifs. Conserved motifs consisting at least nine-mers common across all RV-A or B serotypes were selected and synthesized chemically. Four tagged full-length genes coding the capsid proteins of an ideal strain (HRV-74), VP1, VP2, VP3, and VP4 were constructed and cloned in vitro. Upon expression , the purified recombinant proteins were also administered subcutaneously to other groups of rabbits. The responses and cross-reactivity of the specific immunoglobulin M (IgM) and G (IgG) to the peptides, proteins, and whole viruses were measured. Results: The obtained anti-peptide antibodies exhibited a cross-neutralizing activity for different RV strains in vitro. Antibodies raised to the synthetic peptides exhibited cross-reactivity against the corresponding recombinant proteins and antigenically distinct RV strains coated on plates via ELISA assay. Conclusions: The study findings indicated that the peptides corresponding to the conserved region of the RV capsid proteins were potent immunogenic; moreover, the findings showed that their combination was crucial for extending the cross-protection against variant RVs.

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Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence

European Respiratory Journal ◽

10.1183/09031936.00215114 ◽

2015 ◽

Vol 46 (3) ◽

pp. 771-782 ◽

Cited By ~ 25

Author(s):

Antoine Guillon ◽

Youenn Jouan ◽

Deborah Brea ◽

Fabien Gueugnon ◽

Emilie Dalloneau ◽

...

Keyword(s):

Chronic Obstructive ◽

Dependent Lung ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

Interleukin 22 ◽

Copd Patients ◽

Acute Exacerbations ◽

Underlying Mechanisms

Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infection-driven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling.Using in vitro and in vivo approaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promote IL-22R expression in human bronchial epithelial cells, whereas Pseudomonas aeruginosa, bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as β-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations.Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations.

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The Role of Non-Typeable Haemophilus influenzae Biofilms in Chronic Obstructive Pulmonary Disease

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.720742 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jake R. Weeks ◽

Karl J. Staples ◽

C. Mirella Spalluto ◽

Alastair Watson ◽

Tom M. A. Wilkinson

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Haemophilus Influenzae ◽

Pulmonary Disease ◽

Interspecific Interactions ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Acute Exacerbations

Non-typeable Haemophilus influenzae (NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD). COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation. Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD. NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts. However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa as the cause. NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility. There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD. NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes. These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix. These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including S. pneumoniae and M. catarrhalis. Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or in-vitro bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied. This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung. Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets.

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