Difference between revisions of "Part:BBa K3504011"

Revision as of 08:53, 22 October 2020

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. 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