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This review explores the challenges and strategies in oral delivery of peptide and protein therapeutics. Physiological barriers such as the gastrointestinal tract, enzymatic degradation, poor permeability and proteolytic environment hinder effective delivery. Formulation approaches including bioavailability enhancement, mucoadhesive systems, nanoparticle-based, lipid-based, and polymer-based delivery systems have shown promise in improving solubility, stability, and permeability. Innovative technologies like nanotechnology-based delivery, targeted approaches, drug-device combinations, and bioadhesive/mucoadhesive technologies offer new avenues for overcoming challenges. Strategies to combat enzymatic degradation involve protease inhibitors, enzyme-resistant formulations, chemical modifications, and encapsulation strategies. Enhancing permeability across the intestinal epithelium can be achieved through absorption enhancers, carrier-mediated transport systems, tight junction modulators, and nanotechnology-based approaches. Preclinical and clinical studies provide insights into oral delivery efficacy, safety and patient acceptance. Future directions include advances in delivery, emerging technologies, regulatory considerations and patient compliance. This review offers a comprehensive overview for researchers and clinicians in the field. [ABSTRACT FROM AUTHOR]

Vaccines have significantly reduced the impact of numerous deadly viral infections. However, there is an increasing need to expedite vaccine development in light of the recurrent pandemics and epidemics. Also, identifying vaccines against certain viruses is challenging due to various factors, notably the inability to culture certain viruses in cell cultures and the wide-ranging diversity of MHC profiles in humans. Fortunately, reverse vaccinology (RV) efficiently overcomes these limitations and has simplified the identification of epitopes from antigenic proteins across the entire proteome, streamlining the vaccine development process. Furthermore, it enables the creation of multiepitope vaccines that can effectively account for the variations in MHC profiles within the human population. The RV approach offers numerous advantages in developing precise and effective vaccines against viral pathogens, including extensive proteome coverage, accurate epitope identification, cross-protection capabilities, and MHC compatibility. With the introduction of RV, there is a growing emphasis among researchers on creating multiepitope-based vaccines aiming to stimulate the host's immune responses against multiple serotypes, as opposed to single-component monovalent alternatives. Regardless of how promising the RV-based vaccine candidates may appear, they must undergo experimental validation to probe their protection efficacy for real-world applications. The time, effort, and resources allocated to the laborious epitope identification process can now be redirected toward validating vaccine candidates identified through the RV approach. However, to overcome failures in the RV-based approach, efforts must be made to incorporate immunological principles and consider targeting the epitope regions involved in disease pathogenesis, immune responses, and neutralizing antibody maturation. Integrating multi-omics and incorporating artificial intelligence and machine learning-based tools and techniques in RV would increase the chances of developing an effective vaccine. This review thoroughly explains the RV approach, ideal RV-based vaccine construct components, RV-based vaccines designed to combat viral pathogens, its challenges, and future perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)