Improving Multi-Epitope Long Peptide Vaccine Potency by Using a Strategy that Enhances CD4+ T Help in BALB/c Mice

Abstract

Peptide-based vaccines are attractive approaches for cancer immunotherapy; but the success of these vaccines in clinical trials have been limited. Our goal is to improve immune responses and anti-tumor effects against a synthetic, multi-epitope, long peptide from rat Her2/neu (rHer2/neu) using the help of CD4+ T cells and appropriate adjuvant in a mouse tumor model. Female BALB/c mice were vaccinated with P5+435 multi-epitope long peptide that presents epitopes for cytotoxic T lymphocytes (CTL) in combination with a universal Pan DR epitope (PADRE) or CpG-oligodeoxynucleotides (CpG-ODNs) as a Toll-like receptor agonist adjuvant. The results show that vaccination with the multi-epitope long peptide in combination with the PADRE peptide and CpG-ODN induced expansion of subpopulations of CD4+ and CD8+ cells producing IFN-γ, the average tumor size in the vaccinated mice was less than that of the other groups, and tumor growth was inhibited in 40% of the mice in the vaccinated group. The mean survival time was 82.6 ± 1.25 days in mice vaccinated with P5+435 + CpG+ PADRE. Our results demonstrate that inclusion of PADRE and CpG with the peptide vaccine enhanced significant tumor specific-immune responses in vaccinated mice.

Synergistic effects of anti-PDL-1 with ablative radiation comparing to other regimens with same biological effect dose based on different immunogenic response

“…For tumor induction, 1 × 10 6 CT26 tumor cells were inoculated subcutaneously into the right flank of anesthetized mice as described [18]. Tumor volumes (mm 3 ) were calculated with formula length × width × height × 0.52 that measured by a digital caliper.…”

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

“…Recall epitope assay indicated that 4 of the 5 epitopes successfully activated T cells and challenge assay results showed early activation of T H cells, elevated interferon and interleukin expression, and prolonged survival rates in vaccinated mice (202). Other studies have observed similar, positive results when employing this approach to targeting T cell activation (203)(204)(205)(206).…”

Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine

“…Suitable linkers and adjuvants were used to combine top finalized epitopes from each protein that led to develop a multi epitope vaccine molecules ( Supplementary Table 6). As PADRE sequence was usually recommended to lessen the polymorphism of HLA molecules in the population (Ghaffari-Nazari et al, 2015), it was also considered to construct the final vaccine molecule. Here, adjuvants would enhance the immunogenicity of the vaccine constructs and appropriate separation of epitopes in the host environment would be ensured by the linker (Yang et al, 2015).…”