Improving Protection to Prevent Bacterial Infections: Preliminary Applications of Reverse Vaccinology against the Main Cystic Fibrosis Pathogens

Abstract

Reverse vaccinology is a powerful tool that was recently used to develop vaccines starting from a pathogen genome. Some bacterial infections have the necessity to be prevented then treated. For example, individuals with chronic pulmonary diseases, such as Cystic Fibrosis, are prone to develop infections and biofilms in the thick mucus that covers their lungs, mainly caused by Burkholderia cepacia complex, Haemophilus influenzae, Mycobacterium abscessus complex, Pseudomonas aeruginosa and Staphylococcus aureus. These infections are complicated to treat and prevention remains the best strategy. Despite the availability of vaccines against some strains of those pathogens, it is necessary to improve the immunization of people with Cystic Fibrosis against all of them. An effective approach is to develop a broad-spectrum vaccine to utilize proteins that are well conserved across different species. In this context, reverse vaccinology, a method based on computational analysis of the genome of various microorganisms, appears as one of the most promising tools for the identification of putative targets for broad-spectrum vaccine development. This review provides an overview of the vaccines that are under development by reverse vaccinology against the aforementioned pathogens, as well as the progress made so far.

Phage Therapy: An Alternative Approach to Combat Multi-drug Resistant Infections in Cystic Fibrosis

“…Among the pathogens that generally infects pwCF Staphylococcus aureus, Pseudomonas aeruginosa, Hemophilus influenzae, Mycobacterium abscessus (Mab) and Burkholderia cepacia complex (Bcc) are the main bacteria [13,14]. These pathogens are difficult to treat since their intrinsic and acquired resistance to antibiotic or different strategies to avoid the host's immune system.…”

“…P. aeruginosa is today one of the most studied microorganisms and one the main pathogens of pwCF [14]. Its plastic genome, featured by numerous virulence factors both intrinsic and acquired, confers to this bacterium a high adaptability to the environment, such as the thick mucus of pwCF [26].…”

“…Its genomic plasticity was causative of the acquisition of different virulence factors and drug resistances, so that multi-drug resistant S. aureus and hypervirulence strains are nowadays a challenging concern for human health [30]. For example, the widespread methicillin-resistant S. aureus (MRSA) may cause infections in skin and soft tissues as well as endocarditis, bacteremia, and osteomyelitis [14,31].…”

Burkholderia pseudomallei Complex Subunit and Glycoconjugate Vaccines and Their Potential to Elicit Cross-Protection to Burkholderia cepacia Complex

“…Therefore, some researchers have proposed repurposing Bpc-specific vaccines to treat Bcc infections as a feasible and economically viable solution [ 45 , 46 , 47 ]. One study recently broke down the cost effectiveness of developing and testing a melioidosis-specific vaccine, ultimately concluding it to be a cost-effective strategy of reducing disease incidence [ 48 ].…”

The role of non-typable Haemophilus influenza in recurrent otitis media in children

“…Antibiotics are the primary treatment for NTHi infections, but there is growing concern about the rapid increase in antibiotic and multi-drug-resistant bacteria. Hence, there is an urgent need for enhanced or alternative treatment methods for these illnesses [5,6].…”