Evaluation of immune responses induced by a novel human papillomavirus type 16 E7 peptide-based vaccine with Candida skin test reagent as an adjuvant in C57BL/6 mice

Abstract

Cell mediated immune (CMI) responses are crucial for the clearance of human papillomavirus (HPV) infection and HPV-associated lesions. Activated CD8 T cells are critical effector cells in recognizing and killing HPV-infected or HPV-transformed cells. CD4 T cells provide help for priming the generation and maintenance of CD8 T cells as well as for tumors immunity. An ideal therapeutic HPV peptide-based vaccine should induce both a robust CD8 T-cell response as well as a CD4 T-cell response for ensuring their efficiency. Candida skin test reagent was demonstrated to be able to induce the secretion of IL-12 by Langerhans cells and T-cell proliferation in vitro by our group, which indicated the potential of Candida to enhance CMI response. In this current study, we designed a novel HPV peptide-based vaccine which includes HPV16 E7 peptides and Candida as an adjuvant. The immune responses induced by the vaccine were comprehensively evaluated. The results showed that the vaccine induced significant HPV-specific CD8 T-cell and Th1 CD4 T-cell responses as well as humoral immune response. It is interesting that Candida alone induced a significant polarization of Th1 response an production of IFN-γ, which indicated Candida alone may be used as a potential immunotherapeutic reagent not only for HPV-associated lesions but also for other viral infection or even cancers.

Pulsed-dye laser versus intralesional Candida albicans

“…Considering the oncogenic potential of some HPV strains affecting the genital area, an additional anti-oncogenic role of C. albicans antigen immunotherapy might be suggested. Because of the immune-enhancing capability of recall antigens such as the C. albicans antigen, which induces wart regression, some authors tried using it as a novel adjuvant to HPV therapeutic vaccine for biopsy-proven cervical intraepithelial neoplasia 2/3 (39,40). Wang et al (41) demonstrated significantly up-regulated CD40 and CD80 levels after C. albicans antigen injection, indicating maturation effects of the peptide on Langerhans cells with secretion of IL-12 in addition to T-cell proliferation.…”

“…Wang et al (41) demonstrated significantly up-regulated CD40 and CD80 levels after C. albicans antigen injection, indicating maturation effects of the peptide on Langerhans cells with secretion of IL-12 in addition to T-cell proliferation. In a recent study, C. albicans antigen immunotherapy was found to induce a significant polarization of Th1 response with production of IFN-γ, which indicated that C. albicans antigen may be used solely as a potential immunotherapeutic reagent not only for HPV-associated lesions but also for other viral infection or even cancers (39).…”

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

“…2 Studies have shown that Th1 cells and CD8+ T cells play an important role in resisting HPV infection. 3,4 Persistent HPV infection weakens the functions of Th1 cells and CD8+ T cells in patients, which eventually leads to imbalance of immune responses. 5 However, in the process of cervical cancer caused by HPV, the mechanism of inducing T-cell dysfunction and promoting the immune escape of tumor cells is still unclear.…”

Photodynamic and Cold Atmospheric Plasma Combination Therapy Using Polymeric Nanoparticles for the Synergistic Treatment of Cervical Cancer

“…The viral oncoprotein E7 is highly conserved and only constitutively expressed in HPV-infected or HPV-transformed cells, but not in normal cells [ 27 ]. Oncoprotein E7 can bind to the human epidermal growth factor receptor 3 (HER3) overexpressed in HPV-positive cancer cells [ 28 , 29 ].…”