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

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 vaccines can benefit from an improved antigen format, based on the inclusion of defined helper epitopes and ER targeting.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Ip PP,Boerma A,Walczak M,Oosterhuis K,Haanen JB,Schumacher TN,Nijman HW,Daemen T

doi

10.1038/gt.2015.24

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

560-7

issue

7

eissn

0969-7128

issn

1476-5462

pii

gt201524

journal_volume

22

pub_type

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