Part:BBa_K3504011
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. Through the help of the EAAAK linker at the start (to the MEV N-terminal) the adjuvant (45 amino acid long β-defensin) was bound. EAAK linker is found to increase stability and reduces connection with other protein areas with efficient detachment. There is a possibility that the immunogenicity could increase with an adjuvant. Based on the interactions’ compatibility epitopes were merged together sequentially with AAY and GPGPG linkers, respectively. In the construction of multiepitope vaccines AAY and GPGPG have a main task to prevent the production of junctional epitopes and also promote the immunization and the presentation of epitopes. CTL-epitopes were coupled with AAY linkers and HTL epitopes were coupled with GPGPG and that permitted proficient dissociation and epitope identification. A natural link was established among both innate and adaptive immune responses through Heat-shock proteins(hsp) by merging the idyllic properties of antigen carriage (chaperoning), targeting and activation of antigen-presenting cells (APC), including dendritic cells (DC). The uptake of hsp complexes by DC allows proficient capture and presentation of pathogen-specific antigens and also permits the mounting of a specific immune response by the production of CD4+ T-cell responses. 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
- 10INCOMPATIBLE WITH RFC[10]Illegal PstI site found at 120
- 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 120
Illegal NotI site found at 44 - 21COMPATIBLE WITH RFC[21]
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 120
- 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 120
- 1000INCOMPATIBLE WITH RFC[1000]Illegal BsaI.rc site found at 584
Illegal BsaI.rc site found at 935
Illegal SapI.rc site found at 853
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