Vaccination With Human Papillomavirus Type 16 E7 Peptide With CpG Oligonucleotides for Prevention of Tumor Growth in Mice

Abstract

Objective: To test whether an E7 peptide/CpG vaccine is effective in preventing and treating human papillomavirus-positive tumors in a murine model. Intervention: First, an E7 peptide/CpG vaccine was administered systemically on days −14 and −7, and tumor cells were injected subcutaneously on day 0. Second, tumor cells were injected on day 0, and vaccine was administered on days 7, 14, and 21. Main Outcome Measures: Tumor size was measured 3 times per week. A tetramer assay was used to assess the presence of activated, E7-specific lymphocytes in spleen and tumor cells harvested from mice treated with a similar vaccination regimen. Results: In the prophylactic study, 75% of mice injected with E7 peptide/CpG resisted tumor formation. In the therapeutic setting, tumors initially regressed and experienced delayed progression when compared with controls. Survival rates improved in E7/CpGvaccinated mice. Tetramer analysis detected increased numbers of activated, E7-specific lymphocytes in the spleens and tumors of animals treated with the experimental vaccine when compared with controls. Conclusion: The use of CpG motifs as an adjunct to peptide-based immunotherapy has potential impact on the treatment of human papillomavirus-associated cancers.

Exploration of the nanomedicine-design space with high-throughput screening and machine learning

“…As our test case, we chose the OVA 257–264 peptide from ovalbumin—a well-studied model antigen. Since peptide properties can vary dramatically with amino acid composition, we also tested a peptide antigen from the E7 protein of human papillomavirus17. To study how the release rate of the antigen influences nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation, we evaluated SNAs wherein the antigen was either encapsulated within the SNA architecture or chemically conjugated to oligonucleotides complementary to the CpG oligonucleotides and associated with SNAs through nucleic acid hybridization.…”

Development of HPV16,18,31,45 E5 and E7 peptides-based vaccines predicted by immunoinformatics tools

“…For instance, a study showed that the intranasal administration of the combined HPV16 peptide vaccine [E7 44-62 peptide (QAEPDRAHY-NIVTFCCKCD); E7 49-57 peptide (RAHVYNIVTIF); E6 43-57 peptide (QLLRREVYDFAFRDL); and E6 49-58 peptide (VYDFAFRDLC)) with a4-1BB and aCTLA-4 antibodies produced efficient therapeutic effects and high safety against orally implanted mEER tumors (Dorta-Estremera et al 2018). Moreover, the use of CpG motif (ODN1826: 5 0 -TCCAT-GACGTTCCTGACGTT-3 0 ) as an adjuvant with E7 peptide-based immunotherapy (The H-2b-restricted E7 CTL epitope: RAHYNIVTF) led to reduce the tumor growth (Gendron et al 2006). Other study showed that the conjugation of HPV16 E7 long peptide (E7 43-77 : GQAEPDRAHY-NIVTFCCKCDSTLRLCVQSTHVDIR) to ultrasmall polymeric nanoparticles could enhance the antitumor effects in different mouse models of HPV ?…”

Bone marrow vaccination: A novel approach to enhance antigen specific antitumor immunity

“…Nearly 40% of activated T cells were antigen specific within the BM. This percentage, achieved with only two weekly vaccinations, is much higher than the percentage of Ag-specific cells found in any other organ after peripheral vaccination with the same peptide [16]. This high percentage may be due to proliferation of antigen-specific T cells within the BM.…”