How long do adenoviral vector vaccines typically persist in human tissues in published pharmacokinetic studies?

1. What the data actually measure: genomes, transcripts, antigen and immune readouts

Most studies report persistence by detecting vector DNA or low-level transcriptional activity and by linking that residual expression to sustained CD8+ T cell responses, not by measuring infectious virus titers or classic drug plasma half‑lives; authors therefore describe “persistence of vector genomes” and “transcriptionally active” DNA in muscle, liver and lymphatic tissues rather than continuous high‑level replication ^{[2] [1] [3]}.

2. Typical tissues where vectors are found long-term

Biodistribution work repeatedly shows the injection site muscle, liver (including Kupffer cells and hepatocytes), spleen and lymphoid tissues are the main sinks for adenoviral vectors after systemic or intramuscular delivery; the liver in particular rapidly sequesters a large fraction of vector particles, while the spleen and lymphatics retain viral genomes at higher per‑tissue concentrations in many animal studies ^{[5] [6] [1]}.

3. How long “low‑level persistence” lasts in published studies

Animal and human‑tissue recovery studies report persistence measured in months to years: replication‑defective vectors have been found at the inoculation site, liver and lymphatic tissues for months and, in some reports, genomes can be recovered from lymphatic tissues years after acute adenoviral infection or vector administration ^{[1] [2] [3] [4]}. Reviews and primary experiments frame this as “low‑level” or episomal persistence sufficient to maintain antigen production and active effector T cells over long intervals ^{[2] [1]}.

4. Quantitative limits and the human evidence gap

While multiple sources document long tails of detectability, careful quantification in humans is sparse: most human clinical trials report tolerability and immune responses but do not publish comprehensive tissue‑by‑timepoint pharmacokinetic series that would mimic small‑molecule PK studies, so estimates are extrapolated from animal models plus occasional human tissue recoveries and historical studies of wild‑type adenovirus persistence ^{[7] [4] [3]}.

5. Implications: why persistence matters—and competing perspectives

Persistent low‑level antigen expression is presented as an advantage for durable T‑cell immunity in vaccine design, explaining why adenoviral vectors sustain effector responses better than some other platforms ^{[2] [8]}. At the same time, persistence was a concern in early gene‑therapy work—immune responses, cytotoxicity and theoretical oncogenesis contributed to caution and reduced use in certain gene‑therapy contexts ^[9]. Those competing agendas—maximizing durable immunity versus minimizing long‑term vector presence—drive engineering strategies and study designs ^{[10] [6]}.

6. Safety notes and rare events

Adenoviral vectors generally remain episomal and lack a dedicated integration mechanism; experimental estimates place integration frequencies very low (median ≈0.01% per transduced cell in some studies), but authors note theoretical risks and call for long‑term follow‑up because absolute exclusion of rare events would require very large datasets ^{[8] [11]}.

7. Bottom line—direct answer to the question

Published pharmacokinetic and biodistribution literature shows adenoviral vector genomes and low‑level transcriptional activity are typically detectable in injected muscle, liver and lymphoid tissues for months and can persist at low levels for years in some studies; however, systematic human PK time‑series are limited, so most precise duration estimates rely on animal data and scattered human tissue recoveries rather than standardized human tissue pharmacokinetic trials ^{[1] [2] [3] [4]}.