Vaccine Research
Vaccine Research
vacres
Medical Sciences
http://vacres.pasteur.ac.ir
1
admin
2383-2819
2423-4923
10.61186/vacres
en
jalali
1400
3
1
gregorian
2021
6
1
8
1
online
1
fulltext
en
Potent Therapeutic Efficacy of a Novel HPV16E7-HBcAg-Hsp65 Fusion Protein Vaccine
Prophylactic and therapeutic, and plant-based vaccines
Prophylactic and therapeutic, and plant-based vaccines
Original article
Original article
<strong>Introduction: </strong>Cervical cancer is the fourth leading cause of cancer death in women worldwide. Nearly all cervical cancers are resulted from high-risk Human Papillomavirus (HPV) infection. Currently, there is no available HPV-specific therapy. Cancer therapeutic vaccines have shown anti-tumor efficacy in preclinical animal models as well as clinical patients. <strong>Methods:</strong> Here, we used a previously-reported therapeutic vaccine candidate (VR<sub>111</sub>) based on HPV16E7-HBcAg-Hsp65 fusion protein (with aluminum hydroxide adjuvant) and injected mice with 2 doses of VR<sub>111</sub> at a two-week interval 2 days after TC-1 tumor cell implantation. Tumor growth and animal survival rates were monitored and the vaccine-associated immune responses were evaluated by cytotoxic T lymphocytes assay, T-cell proliferation assay and CD4<sup>+</sup>/CD8<sup>+</sup> T-cell depletion. <strong>Results:</strong> In TC-1 tumor murine model, VR<sub>111</sub> vaccine showed potent dose dependent therapeutic efficacy against tumor growth and improved survival rates in the medium (10 μg) and high doses (30 μg). The three fusion components of VR<sub>111</sub> were all necessary to induce the best anti-tumor activity, CTL response and T cell proliferation. The tumor growth inhibition and a higher mouse survival rate were among the beneficial effects of cisplatin-based combination treatment. Moreover, the anti-tumor potency of VR<sub>111</sub> vaccine was proved to be significantly associated with E7 specific CD8<sup>+</sup> T cell immune response and the adoptive lymphocyte transfer therapy also showed tumor growth inhibition. <strong>Conclusion:</strong> The results confirmed VR<sub>111</sub> as a potent therapeutic HPV vaccine candidate with superior anti-tumor efficacy in a murine model of HPV-induced cancer which its potentials could be considered for combination therapies against cervical cancer.
Human papillomaviruses, Therapeutic vaccine, Cervical caner, T-cell response, Combination therapy
60
66
http://vacres.pasteur.ac.ir/browse.php?a_code=A-10-6049-2&slc_lang=en&sid=1
Chao
Zhang
zhangchao@walvax.com