Core delivery and blood exposure after local vaccination

For a specified core, ask what fraction of the starting peptide copies have delivered that intact core into draining-node APCs by time T? A delivered fragment can be shorter than the input SLP. The reported fraction uses initial peptide molecule counts, not the changing mass of trimmed products. It is separate from the number still present in APCs at T and from surface pMHC.

simulate_vaccine_trajectory now tracks first presence independently of the physical trajectory. summarize_core_exposure(result) exposes this accounting, and vaccine-trajectory --report explains it alongside presentation exposure. All rates and current-fragment assessments still require sources or explicit scenario assumptions. Missing reachable kinetics give an unassessed result.

Four distinct routes to nodal APC antigen

Route	First-presence event
Uptake from node fluid	A core-bearing fragment enters a nodal APC
APC migration	A local APC carries core-bearing antigen or pMHC into the node
Endogenous expression	A nodal APC produces antigen from active vaccine RNA
Cross-dressing	A nodal APC acquires a preformed producer-cell pMHC-I complex

The observer absorbs an antigen lineage at its first event. The physical trajectory continues through processing, secretion or turnover; it cannot add another arrival for the same lineage. RNA remains a repeatable source. Thus RNA outputs report antigen copies per input transcript, which can exceed one, and a separate fraction of antigen produced by the observation horizon. They are never labeled a fraction of injected RNA delivered as peptide.

Blood persistence of a core

Each time point reports blood antigen in two disjoint groups: the exact free core and all longer fragments containing it. Their sum and integrated copy-hour exposure remain available even when the original parent has disappeared.

After IM injection, blood antigen can continue arriving from the injection site, lymph and, for secreted mRNA constructs, producing cells. The whole curve therefore does not identify an intrinsic circulation elimination half-life. The report gives a post-peak half-decline bracket on the observation grid: the first downward crossing of half the largest sampled blood amount, measured from that sampled peak. It neither extrapolates a censored tail nor claims that the peak was resolved between observations. No blood signal or no observed crossing is an explicit status. Refine the grid and inspect the full curve; multiple input phases can cause later rebounds.

mRNA biology and supported routes

Secretion followed by APC uptake is one pathway, not a universal serial model of IM mRNA vaccines. Liang 2017 and Hassett 2024 support direct mRNA uptake/expression at the injection site and in draining nodes. In mouse studies, Rood 2026 found an important role for endogenous APC antigen in MHC-II responses, and Jo 2026 identified a substantial MHC-I cross-dressing contribution. These findings do not identify universal human pathway proportions.

The mRNA antigen-presentation bibliography summarizes these and related primary studies and provides an assay-scoped measurement extract for future calibration. The core-specific calibration audit separates measured pMHC time courses from intrinsic complex lifetimes and gives the physical bounds on first-arrival fractions.

• secreted_mrna follows a supplied signal boundary, ER entry, secretory residence/cuts, secretion, uptake and subsequent APC processing. Failed ER entry and ER-associated retrotranslocation can also feed cytosolic processing.
• cytosolic_mrna places completed antigen in the transfected cell's cytosol. Direct APC processing requires no secretion. Producer-cell release is a separately supplied effective rate; no secretion signal is inferred.
• Both routes can include producer-cell MHC-I processing and transfer of its loaded complex to local or nodal APCs. The modeled donor allele is the specified allele. Transfer does not increment newly loaded APC complexes.

Producer-cell expression, release, processing and transfer require explicit rates and fragment assessments. No MHC-II expression is inferred for non-APC producer cells. Membrane topology, vesicles, debris, APC subsets, changing inflammation and ligand competition are not separately resolved. These are conditional kinetic scenarios, not a calibrated immune-response model.

Version 3.52.0 adds these routes. Older RNA input manifests may therefore need additional explicit rates or declared exclusions. Never replace new unknown rates with zero merely to obtain a numerical output.