Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis

Abstract

The World Health Organization (WHO) herald of the “End TB Strategy” has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led to increased awareness on immunization against Mycobacterium tuberculosis (Mtb). However, the proven limited efficacy of Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mtb, has highlighted the need for alternative vaccines. In this review, we seek to give an overview of Mtb infection and failure of BCG to control it. Afterward, we focus on the protein- and peptide-based subunit vaccine subtype, examining the advantages and drawbacks of using this design approach. Finally, we explore the features of subunit vaccine candidates currently in pre-clinical and clinical evaluation, including the antigen repertoire, the exploited adjuvanted delivery systems, as well as the spawned immune response.

Use of a Novel Peptide Welding Technology Platform for the Development of B- and T-Cell Epitope-Based Vaccines

“…Peptide vaccines have also been advocated for the prevention and treatment of several infectious diseases, including HIV [40][41][42]. For example, the Tat protein has been used in two phase II clinical trials as a therapeutic vaccine against HIV, showing promising results in terms of immunological normalization and viral reservoir reduction [43][44][45].…”

Molecular Epidemiology and Functional Genetics of Mycobacterium Tuberculosis in Humans and Animals

“…These subunit vaccines contain only the immune system stimulatory part of pathogen. Currently, these vaccines are becoming more precise due to the use of only a high binding affinity epitope, instead of using full peptide, that can stimulate the production of antibodies or pro-inflammatory and inflammatory cytokines (Glick et al 2014;Bellini and Horváti 2020;Gong et al 2021). Since subunit vaccines contain only the essential part of antigens, the risks of adverse reaction to the vaccine are lower.…”

“…For designing peptide vaccines, databases are available for the prediction of T and B cell epitopes. The accurate selection of these epitopes is necessary, so that the shortlisted epitopes could have a strong binding affinity with MHC molecule for eliciting immune response (Glick et al 2014;Bellini and Horváti 2020;Gong et al 2021). This subunit vaccine, however, provides excellent protection against Mtb re-infection with excessive amount of IL-1 and IL-17A production.…”

Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable, safe and efficient vaccine adjuvant

“…Vaccines, such as human papillomavirus vaccine [1], hepatitis B vaccine [2], and polio vaccines [3], have been consistently demonstrated to prevent a wide range of infectious diseases and make an indelible contribution to human health. In addition to live attenuated or inactivated vaccines, there is a tendency to extract only the antigenic components of the pathogens, such as purified proteins, polysaccharides, synthetic peptides, and nucleic acids [4][5][6][7]. With simpler structures and higher safety profiles, subunit vaccines were preferred for a quick response to the prevailing pandemic but were at the expense of immunogenicity, as pathogenic structures or components had been removed [8].…”