The development of peptide vaccines has been in the works for a very long time, but with minimal success. However, advancement in medical technology, as well as an increased understanding of the immune system – more specifically the operations of the antigenic epitopes in stimulating an immune response, have opened a whole new field and made the development of peptide vaccines possible. Peptide-based vaccines – technically known as epitope ensemble vaccines, are viewed as a viable alternative approach to the discovery and development of not just disease-specific therapeutics but also prophylactic vaccines.
These vaccines are very different from the other types of vaccines or moieties, which usually use dead or attenuated whole pathogens in the formulation of the vaccines. With this approach, epitopes are viewed as the relevant parts of the antigens commonly referred to as B and/or T cells mediating adaptive immunity. As such, the most promising epitope vaccine ensemble is those that feature desirable B and T cell-mediated immune responses. Also, with peptide-based vaccines, the risks of starting a pathogenic reaction or other undesirable off-target responses are much lower compared to the conventional vaccines. This, hence, brings a lot of credence to these vaccines are they are seen to be safer and more effective compared to the conventional vaccines.
Peptide-based vaccines are also viewed to be very versatile in application and efficacy and it is possible for them to be formulated with the help of synthetic peptides or encoded RNA or DNA formulations. At the moment, there are a plethora of peptide-based vaccines still under development and in different stages of clinical trials. They cover a wide range of diseases, including but not limited to chronic viral infections, as well as cancer vaccines. It is regrettable, however, that none is available at the moment, but there are very good prospects that soon, these revolutionary vaccines will be available. The case for these vaccines, nonetheless, is still very compelling, and it is just a matter of time before the research community comes up with viable and deployable peptide-based vaccines.
The development of a successful peptide-based vaccine features the identification of disease-specific epitopes with the ability to induce immunity protection. This usually involves a number of steps such as determining the appropriate means of how the epitope will be delivered to the disease site and how to overcome the intrinsically low immunogenicity usually witnessed following the isolation of peptides. With the lessons learned from the previous successes in peptide-based vaccines and immunotherapeutics, it is possible to navigate these challenges and make slow but sure steps toward the development of these vaccines.
The main issue when it comes to the development of a peptide-based vaccine is epitope prediction with the help of peptide databases. Peptide databases that contain information on B and T cell epitopes, as well as peptide binding to MHC molecules, are invaluable tools when it comes to the evaluation of immune responses, analyzing predictive methods, creating new ones, and in the design of peptide-based immunotherapeutics. Presently, there are various resources on the internet where you could find such information. However, the best place to check would be the Immune Epitope Database – IEDB. This happens to be the largest and most comprehensive epitope database in the world. With a proper understanding of how data can be entered into and retrieved from this database, it becomes possible to predict B and T cell epitopes with the help of relevant antigens, as well as bioinformatics tools.
In some of the research done on peptide-based vaccines, some researchers focus on the use of computational vaccine design. In one of the studies done by A. R. Oany et al. there was a proposal of a peptide vaccine candidate for shigellosis. This featured a total of four cytotoxic T cells, also known as CTL epitopes. The epitopes were obtained from a SigA antigen, which is known to be highly immunogenic. The four candidates were preserved among the Shigella species, which offered an incredibly wide range of population coverage. Additionally, the researchers in this study determined that MHC II molecules could also be used as CTL epitopes, which would then be used to stimulate T helper responses.
In another study conducted by J. Alonso-Padilla et al. studies that rely on the use of experimentally defined T-cell epitopes were expanded to include the formulation of a prophylactic epitope vaccine that could be used to combat EBV infection, which featured both T and B cell epitopes. It should be noted that in this study, the T-cell component featured experimentally defined CD4 and CD8 B cell epitopes, obtained from a variety of EBV antigens that were conserved and presented by a large number of human MHC molecules. The B-cell component, on the other hand, featured experimental B-cell epitopes that were mapped on the ectodomain of EBV envelope proteins. These exhibited a very high degree of flexibility, and they also exhibited very high solvent accessibility.
In another study conducted by M. Niki et al. there were attempts to identify appropriate antigens that could be used for the formulation of a vaccine for tuberculosis. The study was an extension of a previous study started by the same author where he attempted to do a cross-sectional assay on patients already suffering from TB. In this study, the author considered a different cohort and did a longitudinal assay. In the process, he explored various immunoglobulin responses to antigens and how they correlated to various clinical parameters. From the results obtained, there were a lot of insights that could be used for the development of a novel TB vaccine that could then be used as a viable candidate for inducing protective humoral immunity.
It should be noted that peptide-based immunotherapies and dendritic cells always go hand in hand. J. Lo et al. investigated whether dendritic cells – pulsed or unpulsed with antigenic dominant determinant, ignored determinant, and subdominant determinant, could prevent Type 1 Diabetes in rat models. The results showed that the onset of diabetes was significantly delayed by dendritic cells pulsed with subdominant determinant and ignored determinant. It was also observed that Tregs from mice with dendritic cells multiplied more actively, and they had impressive immunosuppressive activities. The study observed that dendritic cell therapies had the potential of causing long-lasting immunomodulatory effects. This gave a lot of credence to DC-guided peptide-based interventions for autoimmune diabetes.
Toxicity is always a huge challenge in the design and development of vaccines. A. Latanova et al. did some work to try and find solutions to this perennial challenge that has significantly slowed down the development of vaccines. In their study, they fused a flaviviral leader peptide so that it could reverse the transcriptase (RT) – a vital target in immunotherapy on drug-resistant HIV-1. This fusion made it possible for RT secretion, reducing its toxicity and making it possible to induce oxidative stress. The good news is that this didn’t come with any major effects on its immunogenicity. Following the results, the use of leader peptides was proposed as a way of increasing the safety of RT-based DNA vaccines.
Another great obstacle on the path to successful design and development of vaccines is the genetic diversity of pathogens. In a study conducted by V. S. Kichatova et al. the issue was looked into with reference to the human hepatitis C virus. In the study, the authors noted that the occurrence of IFN resistance-conferring mutations in the human hepatitis C virus isolates circulation in Russia. They observed that the virus has many variants whose spread was linked to mutations that took place in the HCV-specific CTL epitopes, in conjunction with an immunogenic background belonging to HCV-infected individuals. The results were immensely helpful in the identification of individuals who needed IFN-free treatments. They also proved to be useful in developing epitope-based vaccines that could be used in circumventing viral immune escape.
S. Oria et al. also studied the effects of combining viral-specific T and B cell epitopes in a proper structure as a way of increasing immunogenicity and enhancing protection. The researchers used the foot-and-mouth disease virus (FMDV). This disease is known to have very high morbidity in cloven-hoofed animals, such as swine and cows. In cows, there exists well known FMDV-specific B and T cell epitopes, which could be candidates for developing safe and more effective vaccines. But successful immunization with the use of linear synthetic peptides featuring these epitopes has not been possible in cattle. In contrast, however, in this study, the researchers immunized cows with dendritic peptide structures that had four copies of a peptide featuring a B-cell epitope that was linked to a single copy of CD4 T-cell epitope with the help of thioether bonds. It was observed that the dendritic peptides created cellular and humoral immune responses, which created partial protection on heterologous virus challenges.
There is still a lot of ongoing work in-progress regarding peptide immunotherapy, and hopefully, there will be major breaks soon. It will be exciting to see the prospects of peptide-based vaccines, and evaluate their success, as well as efficacy in comparison to conventional vaccines.