Peptide Vaccine Development: B And T Cell Epitope Design

Peptide Vaccine Designs and Characteristics

The concept of peptide vaccine designs is based on the chemical process essential for the synthesis of the B and T cell epitopes which are immune dominant and can elicit specific immune responses. The T cells are peptide fragments while the B cell is lipids, proteins, carbohydrates or nucleic acids (Dermime et al., 2004, Sundaram, Beebe and Kaumaya, 2004). Peptides have desirable qualities due to their easy production, chemical nature stability, construction and lack of infectious materials.  

the characteristics feature of the B cell epitope prediction can use with a specificity of 75% with isotopes visible to the outer surface and the intracellular epitopes can be eliminated, antigenicity tests can be done in design the chosen epitopes (Doytchinova and Flower). Recognition of the B cell epitope in this process depends on the flexibility, accessibility of surface, antigenicity, hydrophilicity and linear epitope predictions (Audrey and Procter, 2015). With regard to discontinuous epitopes having higher dormant attributes of over linear epitopes, the need for the forecast is essential, setting high specificity and sensitivity for this case is essential.

The T cell epitope is ideal for the peptide base vaccine, especially its designation. The T cell epitope lowers the cost and time as compared to laboratory wet experiments (Zhang et al., 2004). In this process target protein MHC class, I and MHC class II are essential in the processes which are its targets. The key aspects of the T cell epitope are the mutation, digestion, toxicity, allergenicity, hydro and physiochemical properties. High antigenicity B cell epitopes play a crucial role in initiating an immune response (Audrey and Procter, 2015).

Studies have demonstrated that ‘QLQMGFGITVQYGT’ can yield high immunogenicity with scores of 1.5236 and represent a likely B cell epitope and a candidate for vaccine development. Further, the T cell antigenic has the ability to bind the MHCI and MHCII. Prediction studies have shown that they can interact with the other HLA alleles with high antigen city (Li et al., 2018). Conserved peptides have been demonstrated to have high immunogenicity scores and conservation of the sequence, thus the likelihood of being immunogenic.

Preliminary studies were undertaken with regard the MERS-COV have shown that the sequence, structure, interaction and conservation of B and T cells epitopes have the potential of being vaccine candidates due to their immunogenicity ability (Audrey and Procter, 2015).  Computational studies on B and T cell epitopes obtained from the spike surface of SARS-COV2 based on various physicochemical parameters, ‘SGTNGTKRFDN’ and ‘ASVYAWNRK’ for B cell epitope and T cell epitopes comprising of ‘RLFRKSNLK’ and ‘IPTNFTISV' were identified as potential for peptide-based vaccines. Simulation assays have demonstrated that T cell epitopes tend to have free binding energy which shows string interaction of hydrogen bonds which offer strength for epitope vaccine design formulation. This avenue offers fundamental pathways for developing peptide-based vaccines encompassing the B and T cell epitope designs in their formulation design (Singh, Malik and Raina, 2021).

Studies have shown that peptides may have antipeptide antibodies which play a crucial role in the reaction of cognate protein conferring protective immunity actions making it a good candidate for vaccine development as affirmed by the proteins B and T cell epitopes present (Caoili, 2010).

B cell Epitope Prediction

A conformational epitope entails a sequence of subunits commonly amino acids which have an antigen which comes into contact with immune system receptors. Proteins comprise of repeating nitrogen-containing amino acids which in nature do not exist as straight chains but occur as folded whorls and complex loops, which form the tertiary structure. Thus when the receptors interact with undigested antigens, the surface amino acids may not become continuous with each other. These discontinuous amino acids together with the three-dimensional conformation interact with receptor paratope leading to conformational epitopes. When the digested antigen, the peptides are formed binding the histocompatibility molecule complex and later with the T cell receptors which are continuous forming linear isotopes.

In essence linear be cell isotope forms a contiguous amino acids segments in the antigen while conformational be cell epitope is found in the protein sequence levels. majority of the b cell epitopes are often conformational (Zheng et al., 2015). The conformational isotope with the neighbouring amino acids found in the protein surface structures binds with the complementary paratopes in the b cell receptors and the antibodies play a role in immunology development and vaccine design, especially in peptide-based concepts. An isolated linear epitope lacks the conformational information, hence being flexible and can adapt the conformation thus forming weaker interaction with complementary antibodies (Lo et al., 2021).

In this regard confirmation epitopes have been demonstrated to play critical roles in terms of its properties and association with the B cell epitopes which have antigen protective ability. These properties are essential for vaccine development and drug design which can impact more on-time reduction and cost. Application of these concepts in the peptide vaccine development will be essential due to its prediction performance and advanced applications in the field of immune informatics research and vaccine design.

The application of generating synthetic peptides for antibodies has increased in the recent past. The advantages of peptides instead of the proteins entail the readily available nature and the production easiness of the anti-peptide agents a specific protein isoform. Traditional practice has entailed dissolution of the phosphate-buffered saline and then mixed with m-maleimidobenzoic acid N-hydroxysuccinimide ester (MBS) under BSA conjugates allowing it to form protein conjugated carrier., limited solubility process can be done using 6 M guanidine-HCl/0.01 M phosphate buffer ().

The most common forms of conjugating peptides in larger carrier proteins such as the ovalbumin, bovine serum albumin and Keyhole Limpet Hemocyanin (KLH), are used. The key underlying steps in this process entail;

1. Selection of the protein for application. The most used is the Keyhole Limpet Hemocyanin (KLH). It has higher immunogenicity levels as compared to other proteins and has limited solubility in water and firms' cloudy appearances. The bovine serum albumin protein is stable and soluble form, it has 59 lysines where 30-35 can be accessed. This carrier protein is essential for weak antigen compounds. The ovalbumin protein is isolated from the chicken egg. It is used for controlling carrier protein in verifying antibodies are specific to the target peptide.
2. Peptide designs and synthesis occurs and this depends on the linkage process. the peptides can be synthesized at the right place so as to get optimal surface exposure.
3. Linkage chemistry is applied to the conjugation of protein to protein such as the maleimide based or the hydra link technology. The classical type linkers is able to connect to the protein through the formation of the standard amide bonds binding to any free amine while the peptide is connected to the inker through the addition of the conjugate thiol free to a malemide functionality ability.  This offe3rs a stable peptide-protein linkage which is not easily destroyed by the standard laboratory conditions.
4. Quality control is lastly undertaken to assess the peptide-protein conjugate for direct use. This can be performed by SDS page formation process.

Peptide-based vaccines mimic the epitopes of the antigen thus offering potent immune responses, it induces both protection and effective anti-tumour t cell mechanism responses in the body. In the process of these developments advantages and disadvantages arise with peptide vaccines.

They have various advantages such as;

• The vaccines can be fully synthesized through the chemical synthesis process and can be able to manage the chemical entity.
• In advanced solid phases, peptide synthesis can be produced using microwave and automation techniques.
• They do not have biological contamination as they are chemical synthesis
• The vaccines are soluble in water and can be kept stable in simple conditions
• The peptides can be designed for specificity purposes. They can be designed to have various epitopes to initiate immune responses.
• The vaccine also has short-chain peptide hence lower allergic reaction occurrence or autoimmune response.

The disadvantages are ;

• They have poor immunogenicity aspects.
• They possess unstable cells in the acting mechanism
• They lack native conformation ability
• They are effective for limited population settings.

Thus with these benefits and limitations, peptide vaccine can be applied in wide applications, previously its application in antitumour effects has yielded positive results. Now expanding its use in vaccine formulation with the application of the B and T cell epitopes is likely to play beneficial roles in the drug development and design process in the pharmaceutical process and health care arena. 

References

Audrey, S. and Procter, S., 2015. Employers’ views of promoting walking to work: a qualitative study. International Journal of Behavioral Nutrition and Physical Activity, 12(1), pp.1-10.

Caoili, S.E.C., 2010. Benchmarking B-cell epitope prediction for the design of peptide-based vaccines: problems and prospects. Journal of Biomedicine and Biotechnology, 2010.

Dermime, S., Gilham, D.E., Shaw, D.M., Davidson, E.J., Meziane, E.K., Armstrong, A., Hawkins, R.E. and Stern, P.L., 2004. Vaccine and antibody-directed T cell tumour immunotherapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1704(1), pp.11-35.

Doytchinova, I.A. and Flower, D.R., 2007. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC bioinformatics, 8(1), pp.1-7.

 Li, Y.H., Gao, H., Xiao, Y., Weng, T., Yu, D., Hu, C., Yao, H.P. and Li, L.J., 2018, October. Bioinformatics analysis on potential anti-viral targets against spike protein of MERS-CoV. In 2018 9th International Conference on Information Technology in Medicine and Education (ITME) (pp. 67-71). IEEE.

Lo, Y.T., Shih, T.C., Pai, T.W., Ho, L.P., Wu, J.L. and Chou, H.Y., 2021. Conformational epitope matching and prediction based on protein surface spiral features. BMC genomics, 22(2), pp.1-16.

Singh, J., Malik, D. and Raina, A., 2021. Immuno-informatics approach for B-cell and T-cell epitope based peptide vaccine design against novel COVID-19 virus. Vaccine, 39(7), pp.1087-1095.

Sundaram, R., Beebe, M. and Kaumaya, P.T.P., 2004. Structural and immunogenicity analysis of chimeric B?cell epitope constructs derived from the gp46 and gp21 subunits of the envelope glycoproteins of HTLV?1. The Journal of peptide research, 63(2), pp.132-140.

Zhang, M., Ishii, K., Hisaeda, H., Murata, S., Chiba, T., Tanaka, K., Li, Y., Obata, C., Furue, M. and Himeno, K., 2004. Ubiquitin?fusion degradation pathway plays an indispensable role in naked DNA vaccination with a chimeric gene encoding a syngeneic cytotoxic T lymphocyte epitope of melanocyte and green fluorescent protein. Immunology, 112(4), pp.567-574.

Zheng, W., Ruan, J., Hu, G., Wang, K., Hanlon, M. and Gao, J., 2015. Analysis of conformational B-cell epitopes in the antibody-antigen complex using the depth function and the convex hull. PloS one, 10(8), p.e0134835.