K-Ras Peptide Mimotope Induces Antigen Specific Th1 and B-Cell Immune Responses against G12A-Mutated K-Ras Antigen in Balb/c Mice

• Published in: Vaccines (Basel) Vol. 9; no. 3; p. 195
• Main Authors: Siak, Pui Yan, Wong, Kuan Yee, Song, Adelene Ai-Lian, Rahim, Raha Abdul, In, Lionel Lian Aun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2021; MDPI
• Subjects: Antigenicity; Antigens; Bacteria; E coli; Epidermal growth factor; Epidermal growth factor receptors; Epitopes; Gastrointestinal system; Gastrointestinal tract; Growth factors; Immune response; Immune response (cell-mediated); Immune system; Immunization; Immunogenicity; Immunoglobulin A; Immunoglobulin G; Immunology; Immunomodulation; Immunotherapy; Interferon; K-Ras protein; KRAS; Lactococcus lactis; Lymphocytes B; Lymphocytes T; Monoclonal antibodies; Mutation; Oral administration; peptide-based vaccine; Peptides; Plasmids; Point mutation; Proteins; Survivability; Tetanus; tetanus toxoid; Vaccines; γ-Interferon; United States > US; Germany; peptide-based vaccine; Lactococcus lactis; KRAS; tetanus toxoid
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines9030195

G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, , which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery vehicle. Recombinant strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were immunized orally, and high survivability of passage through the gastrointestinal tract was observed. Elevations in B-cell count with a concomitant titre of antigen-specific IgG and interferon-γ secreting T-cells were observed in the 139A treated mice group. Interestingly, an even higher antigen-specific IgA response and interferon-γ secreting T-cell counts were observed in 139A-TTD mice group upon re-stimulation with the G12A mutated K-ras antigen. Collectively, these results indicated that an antigen-specific immune response was successfully stimulated by 139A-TTD vaccine, and a TTD fusion was successful in further enhancing the immune responses.