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Multi-Epitope TNBC Vaccine Version (1)

Part Description

A multi-epitope vaccine formed of highly expressed and specific TNBC neo-epitopes and specifically chosen according to egyptian population alleles which can work as a generalized vaccine and also personalized vaccine which would illicit an immune response specific to TNBC tumor cells

Usage

Immune-modulating adjuvants and PADRE (Pan HLA-DR epitopes) sequence were added with epitopes sequence to enhance the immunogenicity. All the epitopes, adjuvants and PADRE sequence were joined by linkers. An adjuvant (45 amino acid long β-defensin) was bound with the aid of the EAAAK linker at the start (to the MEV N-terminal). EAAAK linker reduces connection with other protein areas with efficient detachment and increases stability [88,89]. The vaccine’s immunogenicity may increase with an adjuvant. Epitopes were merged together based on their interaction’s compatibility in a sequential manner with AAY and GPGPG linkers, respectively. AAY and GPGPG prevent the production of junctional epitopes, that is the main task in the construction of multiepitope vaccines; on the other hand, they promote the immunization and epitope presentation. Further, CTL-epitopes were connected with AAY linkers and HTL epitopes with GPGPG which permit proficient dissociation and identification of each epitope. To improve the vaccine efficacy and potency non-natural pan DR (PADRE) 13 amino acid epitope (AKFVAAWTLKAAA) that induce CD4+ T-cells were also combined along with the adjuvants. Heat Shock Protein (hsp) was retrieved from the database to design a multi-epitope subunit vaccine containing a CTL, HTL and BCL epitopes of varying length. Heat-shock proteins (hsp) provide a natural link between innate and adaptive immune responses by combining the ideal properties of antigen carriage (chaperoning), targeting and activation of antigen-presenting cells (APC), including dendritic cells (DC). The uptake of hsp complexes by DC enables efficient capture and presentation of pathogen-specific antigens and the mounting of a specific immune response through the generation of CD4+ T-cell responses.

References :

Tahir ul Qamar, Muhammad, et al. “Multiepitope-Based Subunit Vaccine Design and Evaluation against Respiratory Syncytial Virus Using Reverse Vaccinology Approach.” Vaccines, vol. 8, no. 2, 1 June 2020, p. 288, www.mdpi.com/2076-393X/8/2/288/htm, 10.3390/vaccines8020288. Accessed 22 Oct. 2020.

McNulty, Shaun, et al. “Heat-Shock Proteins as Dendritic Cell-Targeting Vaccines - Getting Warmer.” Immunology, vol. 139, no. 4, 2 July 2013, pp. 407–415, 10.1111/imm.12104. Accessed 18 Nov. 2019.

Solanki, Vandana, et al. “Prioritization of Potential Vaccine Targets Using Comparative Proteomics and Designing of the Chimeric Multi-Epitope Vaccine against Pseudomonas Aeruginosa.” Scientific Reports, vol. 9, no. 1, 27 Mar. 2019, 10.1038/s41598-019-41496-4. Accessed 22 May 2020.

Characterization

Improvements

Sequence and Features