The Promising Potential of Reverse Vaccinology-Based Next-Generation Vaccine Development over Conventional Vaccines against Antibiotic-Resistant Bacteria

Abstract

The clinical use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria, leading to the current antibiotic resistance crisis. To address this issue, next-generation vaccines are being developed to prevent antimicrobial resistance caused by MDR bacteria. Traditional vaccine platforms, such as inactivated vaccines (IVs) and live attenuated vaccines (LAVs), were effective in preventing bacterial infections. However, they have shown reduced efficacy against emerging antibiotic-resistant bacteria, including MDR M. tuberculosis. Additionally, the large-scale production of LAVs and IVs requires the growth of live pathogenic microorganisms. A more promising approach for the accelerated development of vaccines against antibiotic-resistant bacteria involves the use of in silico immunoinformatics techniques and reverse vaccinology. The bioinformatics approach can identify highly conserved antigenic targets capable of providing broader protection against emerging drug-resistant bacteria. Multi-epitope vaccines, such as recombinant protein-, DNA-, or mRNA-based vaccines, which incorporate several antigenic targets, offer the potential for accelerated development timelines. This review evaluates the potential of next-generation vaccine development based on the reverse vaccinology approach and highlights the development of safe and immunogenic vaccines through relevant examples from successful preclinical and clinical studies.

Combined Immunoinformatics to Design and Evaluate a Multi-Epitope Vaccine Candidate against Streptococcus suis Infection

“…Compared with traditional inactivated vaccines and emerging mRNA vaccines, multi-epitope vaccines present enhanced immune efficacy and broad-spectrum protection and are low cost [ 59 , 60 ]. Candidate epitope screening determines immunological efficacy and protective coverage, and therefore, highly conserved and immunogenic epitopes need to be prioritized [ 24 , 27 ].…”

Computational design of novel chimeric multiepitope vaccine against bacterial and viral disease in tilapia (Oreochromis sp.)

“…To surpass the hindrances of the traditional approach, recently, the concepts of reverse vaccinology and structural vaccinology have been dramatically introduced in generating novel potential vaccines for both human and veterinary disease prevention. This advanced method benefits in searching the potentially immunogenic targets within the pathogenic genomes before identifying the feasibly antigenic epitopes for developing the promising next-generation vaccine platform, which is the multiepitope-based vaccine 40 . In this regard, we applied an innovative strategy based on the vaccinomics approach to design the polyvalent multiepitope vaccine against the seven causative agents of tilapia fish.…”

A prognostic insight of the mRNA vaccine against antibiotic-resistant bacteria

“…Antigen expression caused by a non-replicating mRNA vaccination correlates with the number of transfected cells, hence a high quantity of mRNA must be injected 31 . For transgenic expression, many vector systems have been employed, including replication-deficient viral particles, replication-competent viral particles, and DNA-launched-mRNA vector techniques 32 , 33 . The engineered DNA-launched-mRNA vectors combined with non-structural proteins (nsp1-4) generate a replicase complex that induces effective transgene expression via a self-amplifying technique 31 .…”