Generation and characterization of a preventive and therapeutic HPV DNA vaccine

Abstract

Cervical cancer is one of the most common cancers in women worldwide. Persistent infection with human papillomavirus (HPV) is considered to be the etiological factor for cervical cancer. Therefore, an effective vaccine against HPV infections may lead to the control of cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infections as well as cell-mediated immunity to eliminate established infection or HPV-related disease. In the current study, we have generated a potential preventive and therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T cell immune response, resulting in a significant therapeutic effect against E6/E7 expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated significant L2-specific neutralizing antibody responses, protecting against pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of generating potent preventive and therapeutic effects in vaccinated mice. Our data has significant clinical implications.

Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus

“…The administration of a quadrivalent prophylactic vaccine (against HPV 6, 11, 16, and 18, the most frequent types in anal lesions) to young men and women might optimize the control of HPV transmission through sex between men and women and between men [33]. New therapeutic HPV-vaccine strategies [34], some of which have been tested for vulvar lesions [35], may be useful for the treatment of recurrent anal lesions, helping to preserve the integrity of the anal sphincter.…”

Prevention of Human Papillomavirus Infections and Associated Diseases by Vaccination: A New Hope for Global Public Health

“…Future vaccine developments are considering different L1 VLPs, adding L1 VLPs or combining prophylactic and therapeutic VLPs. The combination of L1 and L2 viruslike particles has been used in early clinical trials to determine the extension of cross coverage possible by adding the L2 protein immunogen [18] . Another novel vaccine is designed by fusing the L1 protein sequences to the E6 and E7 protein sequences expressed during persistent infection to create a prophylactic and therapeutic vaccine [19] .…”

Short Communication Development of a DNA-based vaccine strategy against bovine papillomavirus infection, involving the E5 or L2 gene

“…Several strategies have been used in the development of different types of vaccine (Kim et al, 2008). DNA vaccines have been considered because they are able to stimulate effective cytotoxic T lymphocyte and antibody responses by delivering foreign antigens to antigen presenting cells that stimulate CD4 + and CD8 + T cells.…”