Advanced Production System to Genetically Stabilize Viral Vectors for Sustained Transgene Expression

Regensburg, May 14^th 2024

Poxviral vectors derived from Modified Vaccinia Virus Ankara (MVA) are widely used for the development of therapeutic and prophylactic vaccines due to their exceptional safe delivery modality, which can even be applied in immunocompromised patients. However, certain transgenes render recombinant MVA (rMVA) genetically unstable and lead to strong negative selection eventually leading to a loss of transgene expression. This hampers the generation, selection and eventually large-scale (e.g. GMP) production of such recombinant viral vectors limiting their use as vaccines.

In a recently published study, Prof. Wagner and his team (Molecular Microbiology / Virology Unit at the Institute of Medical Microbiology and Hygiene, University of Regensburg) evaluated the impact of transgene expression knock-down in a modified avian suppressor production cell line (AGE1.CR.pIX® derivative). In fact, suppressed transgene expression during rMVA generation and production preserved a sustained transgene maintenance across multiple passages. In contrast, rMVA passaged on the parental avian production cell line rapidly acquired mutations and deletions, which abrogated maintenance of the intact transgene.

This study is of general interest in particular for researchers using poxviral vectors for vaccine delivery to combat infectious diseases and fight cancers. This work may have also implications for the improvement of viral vector platforms other than poxviruses including but not limited to e.g. adenoviral vectors.

This study did benefit from an efficient and smooth collaboration between our group and ProBioGen AG, as well as colleagues from the University of Copenhagen (Prof. Peter Johannes Holst) together with SIRION BIOTECH GmbH (Revvity, Inc.) and Hervolution Therapeutics ApS. This work is part of the THERIN EUROSTARS project aming towards a therapeutic HPV vaccine candidates to fight HPV-derived malignancies such as cervical as well as head and neck cancer (link).

Reference:

Neckermann P, Mohr M, Billmeier M, Karlas A, Boilesen DR, Thirion C, Holst PJ, Jordan I, Sandig V, Asbach B, Wagner R. Transgene expression knock-down in recombinant Modified Vaccinia virus Ankara vectors improves genetic stability and sustained transgene maintenance across multiple passages. Front Immunol. 2024 Feb 6;15:1338492. doi.org/10.3389/fimmu.2024.1338492

About:

Wagner-Lab, Molecular Microbiology (Virology), Institute of Medical Microbiology and Hygiene [https://wagner-lab.de]