Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Abstract

Human papilloma-virus (HPV) infection is the major cause of cervical cancer. HPV 18 is the most prevalence high-risk HPV after type 16 that accounts for the largest number of cervical cancer cases worldwide. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines for targeting tumors post infection. In this study, we utilize a novel multi-phase strategy for HPV 18 antigen development with the goal of increasing anti-HPV18 cellular immunity. Our data show that this construct can induce strong cellular immune responses against HPV 18 E6 and E7 antigens in a murine model. Moreover, when applied to Rhesus monkeys, this construct is also able to elicit cellular immunity. These data suggest such DNA immunogens are candidates for further study in the eventual context of immunotherapy for HPV-associated cancers.

Induction of robust cellular immunity against HPV6 and HPV11 in mice by DNA vaccine encoding for E6/E7 antigen

“…23,24 Prior studies examining the immunogenicity of novel DNA vaccines with E6/E7 consensus genes targeting HPV16 and HPV18 have shown much promise for future development into a vaccine for clinical use. 12,13 Ideally, clinical trials in humans would be used as the ultimate test to evaluate the vaccines' efficacy. However, various pre-clinical experiments using other models, including human MHC transgenic animals as well as non-human primates, may generate important data regarding the immune potency of these cassettes.…”

“…Numerous optimization, delivery and boost strategies have been developed and are currently being studied. 8,[12][13][14][15][16][17][18] Recent work on DNA vaccines for HPV therapy have produced promising preliminary results which have now led to clinical trials targeting the HPV 16 or 18 subtypes. [12][13][14][19][20][21][22] However, there have been no prior reports focusing on HPV subtypes 6 + 11.…”

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

“…Dermal immunization methods target the epidermis, the dermis, or both, and include chemical modification, 38,39 transepidermal immunization, 40,41 gene gun technology, 31 electroporation 42,43 and intradermal injections. 42 Recently, intradermal administration with the RNA interference technique has also been reported.…”

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

“…Immunization induced a potent cellular immune response against both E6 and E7 proteins [107], and it was able to delay the growth of established HPV-tumors [108]. Another plasmid encoding E7-speciic CTL epitopes from HPV 16 and 18 and embedded in biodegradable micro particles (ZYC101a) was tested in a group of patients histologically conirmed CIN 2/3 neoplasia.…”