Method validation and assessment of the biodistribution and shedding for adenovirus vector-based vaccine using qPCR and dPCR

Assessment of the biodistribution and shedding is required for the development of viral vector-based vaccines. Vector copy number is commonly quantified using digital PCR (dPCR) or quantitative PCR (qPCR). However, the regulatory guidelines for bioanalytical PCR assays have not been released at pres...

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Bibliographic Details
Main Authors: Yoichi Tanaka, Sayaka Hamano, Akiko Ishii-Watabe, Yoshiro Saito, Ruri Kikura-Hanajiri
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Molecular Therapy: Methods & Clinical Development
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Online Access:http://www.sciencedirect.com/science/article/pii/S2329050125001445
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Summary:Assessment of the biodistribution and shedding is required for the development of viral vector-based vaccines. Vector copy number is commonly quantified using digital PCR (dPCR) or quantitative PCR (qPCR). However, the regulatory guidelines for bioanalytical PCR assays have not been released at present. To consider the future setting of acceptance criteria for method validation in a guideline, we aimed to develop and validate a method for quantifying a model adenoviral (Ad) vector vaccine (Ad-hCovHKU1S-2A-GFP) using dPCR and qPCR in biological matrices and assessed its biodistribution in mice. Primers and probes were designed for the region between the sequences of the Ad and HKU1S. Method development and validation were performed using dPCR and qPCR with 1 μg of mouse genomic DNA (gDNA)/reaction. The validation parameters and their acceptance criteria were pre-defined as possible values referred from the literature. Lower limits of quantitation were set as 12 copies and 48 copies/reaction for dPCR and qPCR, respectively. Both dPCR and qPCR met the pre-defined acceptance criteria for intra- and inter-run accuracy and precision. Cross-validation showed similar quantitative results using both dPCR and qPCR. The pre-defined acceptance criteria on dPCR and qPCR may be applicable to the biodistribution and shedding of viral vector-based vaccines.
ISSN:2329-0501