The Antitumor Effect of a Non-Transforming E7 Protein Combined  with a TLR7 Agonist

Maryam Mashhadi  Abolghasem Shirazi; Seyed Mehdi  Sadat; Nasser Hashemi  Goradel; Arash  Arashkia

doi:10.18502/ijaai.v24i4.19130

Maryam Mashhadi Abolghasem Shirazi Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
Seyed Mehdi Sadat Department of Hepatitis, AIDS and Blood Borne Diseases, Pasteur Institute of Iran, Tehran, Iran
Nasser Hashemi Goradel Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran
Arash Arashkia Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v24i4.19130

Keywords: Epitopes; Human papillomavirus 16; Imiquimod; Uterine cervical neoplasms; Vaccines

Abstract

Despite great efforts in developing peptide-based therapeutic vaccines against human papillomavirus (HPV)-induced cervical cancers, they have failed to elicit strong and sustainable immune responses. Here, we evaluated the vaccine potential of an HPV16 three mutant of E7 (E7GGG) (D21G/C24G/E26G) protein combined with Aldara (topical imiquimod) adjuvant in a TC-1 mouse tumor model.

The HPV16-E7GGG, with eliminated transforming properties but retained antigenicity, and E7 wild-type were inserted into pET28, expressed in the E coli system, and purified using Ni-NTA chromatography. The E7GGG and E7 wild-type proteins were combined with Aldara adjuvant and injected into C57BL mice.

We determined the ability of HPV16-E7GGG in combination with Aldara adjuvant to induce robust immune responses by IgG total development, IL-4, IL-17, and IFN-γ induction, CTL activity, and inhibit tumor growth in the murine TC-1 model in different immunized groups.

The generated recombinant HPV16-E7GGG induced humoral and cellular immune responses in a T_H1-mediated pathway, specifically with the (E7GGG) (D21G/C24G/E26G) antigen combined with Aldara, which could be a suitable therapeutic vaccine candidate against HPV.