Antigen design enhances the immunogenicity of Semliki Forest virus-based therapeutic human papillomavirus vaccines

Gene Therapy
P P IpT Daemen

Abstract

Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the relatively low intrinsic immunogenicity of DNA vaccines could be enhanced by inclusion of endoplasmic reticulum (ER) targeting and universal helper epitopes within the vaccine. We now evaluated whether an optimal antigen format, as defined in DNA vaccines, can further enhance the effectiveness of recombinant Semliki Forest virus (rSFV) vaccines. To this purpose, we generated, characterized and evaluated the efficacy of rSFV replicon particles expressing human papillomavirus E6 and/or E7 proteins fused to several helper T-cell epitopes and an ER targeting signal. Here, we show that inclusion of a helper cassette and an ER targeting signal enhanced protein stability and markedly augmented the frequencies of human papillomavirus-specific T cells. Even at an immunization dose of as low as 10(5) replicon particles, this novel vaccine achieved tumor regression and protection. Thus, even highly effective viral vector vacci...Continue Reading

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Citations

Feb 24, 2016·Expert Review of Vaccines·Andrew YangChien-Fu Hung
Nov 5, 2016·Journal of Biomedical Science·Andrew YangChien-Fu Hung
Nov 23, 2018·Cancer Immunology, Immunotherapy : CII·Amrita SinghToos Daemen
Oct 18, 2019·Therapeutic Advances in Vaccines and Immunotherapy·Georgia KoutsoumpliToos Daemen
Nov 8, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fenne L KomdeurToos Daemen

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