How do biodistribution results for mRNA (BNT162b2/Moderna) differ from adenoviral (Ad26/ChAdOx1) COVID‑19 vaccines in animal studies?
Executive summary
Animal biodistribution studies of mRNA‑LNP and adenoviral COVID‑19 vaccine platforms show different patterns: preclinical data and regulatory summaries indicate mRNA‑LNP signal concentrates at the intramuscular injection site and in liver and draining lymph nodes, whereas adenoviral vectors tend to remain detectable at the injection site and in regional lymphoid tissues with vector DNA persisting locally for weeks and less consistent systemic spread in the datasets reviewed [1] [2] [3]. Interpretation is constrained by heterogenous methods, variable reporters (luciferase, RT‑qPCR, vector DNA), different doses and species, and incomplete public reporting from some regulatory files [1] [4] [3].
1. What the mRNA animal data show: mostly local muscle and liver signal with formulation-dependent variation
Multiple animal studies and manufacturer/regulatory summaries using reporter mRNAs or RT‑qPCR found that, after intramuscular injection, lipid‑nanoparticle (LNP) formulated mRNA gives strong expression at the injection site and detectable expression in the liver and draining lymph nodes; luciferase reporter imaging in mice showed robust signal in muscle and a weaker but reproducible signal in liver within hours [1], and variations in LNP structure and chemistry alter that pattern—some LNP designs report lower liver targeting and more confined distribution [5] [6].
2. What the adenoviral animal data show: persistent local DNA and lymphoid targeting, less clear systemic protein expression
Preclinical biodistribution evaluations of replication‑incompetent adenoviral vectors (ChAdOx1, Ad26 and similar constructs) commonly detect vector DNA and/or antigen expression concentrated at the injection site and in draining lymph nodes, with detectable vector DNA persisting locally for weeks in some studies, implying persistent low levels of antigen presentation; systemic dissemination beyond regional lymphoid tissue is variable across studies and typically lower than the strongest local signals [2] [7].
3. Head‑to‑head contrasts emerge from methods as much as biology: reporters, timing, dose and species matter
Comparisons are complicated because mRNA studies often use luminescent reporter proteins and LNP tracer methods in small rodents or NHPs, while adenoviral studies frequently measure vector DNA persistence and transgene expression with PCR or histology; timepoints differ (hours to days for many mRNA reporter assays versus days to weeks for adenoviral DNA surveys), doses and particle counts are not directly comparable (mRNA µg versus viral particles), and some regulatory preclinical programs were incomplete or poorly disclosed for SARS‑CoV‑2 spike‑encoding mRNA vaccines, limiting definitive cross‑platform claims [1] [4] [3].
4. Biological implications: antigen location, immune priming and rare adverse signals are platform‑dependent but not solely determined by biodistribution
Where antigen is presented helps shape immune priming—mRNA‑LNPs driving strong local protein expression plus lymph node delivery appear to elicit potent humoral responses, while adenoviral vectors producing local persistence of vector DNA and antigen can favor robust cellular immunity; clinical immunogenicity and safety differences (stronger neutralizing antibody titers with mRNA in several comparisons, and distinct rare adverse‑event patterns in epidemiology) track with but are not fully explained by biodistribution alone [8] [9] [10].
5. What the studies do not settle and why caution is required
Public datasets are heterogeneous and incomplete: some regulatory reviewers noted gaps in tissue‑specific distribution for the licensed mRNA COVID‑19 vaccines, and many animal programs use surrogate reporters rather than the exact clinical constructs, so direct extrapolation to humans is limited; consequently, assertions that one platform “travels everywhere” while the other does not are unsupported by the available, methodologically disparate animal data [3] [1] [11].