Seven extracellular proteins and two intracellular proteins were identified as potential vaccine targets for triple-negative breast cancer (TNBC).
A total of 18 MHC-I epitopes, 1 MHC-II epitope, and 2 B-cell epitopes were predicted with significant binding affinity and 87.75% population coverage for the Persian-Iranian cohort.
The developed protein vaccine exhibited favorable physicochemical properties, structural stability, and non-allergenic potential.
TLR4 was identified as the main receptor for adjuvant interaction, with molecular docking showing strong binding strength.
The mRNA vaccine design achieved a Codon Adaptation Index of 0.93, indicating optimization for expression.
Both vaccine formulations demonstrated strong immune stimulation in silico, suggesting their potential for immunotherapy against TNBC.
Simplified
Triple-negative breast cancer (TNBC) represents a particularly aggressive subtype of breast cancer lacking expression of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), leading to restricted treatment options and unfavorable outcomes and prognosis. This research employs and reverse vaccinology strategies to develop novel multi-epitope protein and mRNA vaccines targeting TNBC-associated antigens. By using a detailed scoring system, we identified seven extracellular proteins (TROP-2, EpCAM, MUC1, NECTIN4, Folate Receptor α, Mesothelin, α-Lactalbumin) and two intracellular proteins (MAGE-A, NY-ESO-1) as targets for the vaccine. Through a thorough process of predicting and validating epitopes, we discovered 18 MHC-I epitopes, 1 MHC-II epitope, and 2 B-cell epitopes with considerable binding affinity and population coverage (87.75% for the Persian-Iranian cohort), with an emphasis on the MHC-I pathway. The constructed protein vaccine demonstrated favorable physicochemical characteristics, structural stability, non-toxicity, and non-allergenic potential. TLR4 was found to be the primary pattern recognition receptor for adjuvant interaction, and molecular docking illustrated strong binding strength. In constructing the mRNA vaccine, we included N-5' m7GCap, 5' UTR, Kozak sequence, signal peptide (tPA), MHC epitopes, linker, MITD sequence, stop codon, 3' UTR, and poly-A tail. Consequently, the design of the mRNA vaccine integrated optimized codon sequences with relevant regulatory components, achieving a Codon Adaptation Index of 0.93. Furthermore, we propose an innovative four-part mRNA vaccine approach to balance therapeutic effectiveness with clinical practicalities. Both vaccine formulations showed intense immune stimulation in silico, indicating their potential as promising candidates for immunotherapy against TNBC, which will require further experimental exploration.
Key numbers
87.75%
Population Coverage
Coverage for the Persian-Iranian cohort based on identified alleles.
9
Selected Proteins
Proteins selected for their relevance to TNBC and therapeutic potential.
21
Identified
Including 18 -I, 1 -II, and 2 B-cell .
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