Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

Stephanie Van De Wall,Mateusz Walczak,Toos Daemen,Hans Nijman,Baukje-Nynke Hoogeboom,Nienke Van Rooij,Tjarko Meijerhof

doi:10.3390/vaccines3020221

Stephanie Van De Wall, Mateusz Walczak + Show 5 more

Open Access

https://doi.org/10.3390/vaccines3020221

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Abstract

The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

Highlights

Vaccination in the form of viral vectors serves as a potent strategy for the induction of CD8+ T cell responses in the context of various diseases
A therapeutic immunization strategy based on an alphavirus, Semliki Forest virus (SFV), has been developed for targeting cervical cancer and premalignant cervical lesions induced by Human Papillomavirus (HPV)
We evaluated the efficacy of the SFVeE6,7 vaccine upon skin tattooing in the murine model system and compared it to that of responses induced by intramuscular injection

Summary

Introduction

Vaccination in the form of viral vectors serves as a potent strategy for the induction of CD8+ T cell responses in the context of various diseases. A therapeutic immunization strategy based on an alphavirus, Semliki Forest virus (SFV), has been developed for targeting cervical cancer and premalignant cervical lesions induced by Human Papillomavirus (HPV). We demonstrated that intramuscular immunization of mice with rSFVeE6,7 particles results in strong HPV-specific cellular responses with eradication of established HPV-transformed tumors [1,2]. These strong responses are induced in immune-tolerant mice and the efficacy of SFVeE6,7 immunization is not hampered by immunosuppressive regulatory T cells [3]. Clinical responses are often met with insufficient protection against cancer occurrence where the potency of the vector alone may not be sufficient for protection.

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