Search Results (979)

Measles virus infection couples nonlinear processes across biological scales, including within-host viral amplification, immune-cell depletion, delayed adaptive control, persistent viral RNA, heterogeneous host severity and vaccination-dependent population spread. A multiscale mathematical framework is developed by coupling a seven-variable within-host ordinary differential equation model to a stochastic cellular automaton. The within-host system extends a four-variable measles immunodynamics core by including IFN-$\gamma$-dominant and IL-17-associated immune responses, persistent viral RNA and neutralizing antibodies. Six host archetypes are represented as structured parameter perturbations of this common dynamical core. The principal novelty is an explicit cross-scale coupling operator that separates genuinely ODE-derived host descriptors from hybrid epidemiological mapping rules and independently specified population-level contact and susceptibility assumptions, allowing within-host heterogeneity to propagate transparently into a spatial stochastic epidemic model. An explicit ODE-to-cellular-automaton map translates within-host trajectories into infectious timing, daily infectivity profiles and an illustrative ODE-informed severity-to-death transition mapping used internally by the cellular automaton. The mortality map depends on viral burden, infectious duration, IFN-$\gamma$ deficit, cumulative infectivity and an immune-deficit–infectivity interaction term. Population simulations show a nonlinear reduction in attack rate with increasing vaccination coverage, reduced modeled death burden under targeted high-risk in silico perturbations and additional suppression under reactive vaccination campaigns. A direct local cellular-automaton secondary-infection estimate is reported instead of interpreting cumulative infectivity burden as a reproduction number. A targeted contact-structure sensitivity further shows that matching the expected local direct-secondary-infection potential does not imply equivalent population-level attack rates, emphasizing that the quantitative CA outcomes are geometry specific. Sobol sensitivity analysis with convergence up to $N_{\mathrm{base}}=4096$ identifies core viral and immune parameters as dominant drivers of within-host and multiscale outputs. The framework provides an explicit dynamical-systems approach for coupling differential-equation immunodynamics to spatial stochastic population models in mathematical biology. Full article

Background/Objectives: Streptococcus suis is an important zoonotic pathogen responsible for severe infections in animals and humans, and the emergence of diverse strains has reduced the effectiveness of conventional antimicrobial therapies. Since there is no broadly protective vaccine, there is a need for new vaccination strategies that focus on conserved antigens from a variety of strains. This study aimed to design and evaluate a multi-epitope vaccine candidate against diverse S. suis strains using an integrated pangenome-guided reverse vaccinology approach. Methods: To design a multi-epitope vaccine (MEV) candidate against diverse S. suis, an integrated computational framework was employed, incorporating pangenome analysis, subtractive proteomics, reverse vaccinology, immunoinformatics, structural modeling, molecular docking, molecular dynamics simulation, immune simulation, and in silico cloning. The conserved core proteins were systematically screened for essential, non-homologous, antigenic, non-allergenic and non-toxic vaccine candidates for epitope prediction. Results: A total of 7421 gene families, including 1169 conserved core genes, were identified through pangenome analysis of 24 complete S. suis genomes. Three computationally prioritized candidate proteins were identified through sequential subtractive proteomics: sucrose phosphorylase, peptidoglycan hydrolase PcsB and an RND transporter-associated adaptor protein, annotated in the source database as an RND efflux transporter periplasmic adaptor subunit. We selected eight cytotoxic T-lymphocyte (CTL) epitopes, five helper T-lymphocyte (HTL) epitopes, and three linear B-cell epitopes with favorable predicted immunological properties to develop a 397-amino acid multi-epitope vaccine construct that contains the S. suis 50S ribosomal protein L7/L12 adjuvant with rationally designed peptide linkers. The vaccine construct exhibited favorable physicochemical properties, predicted structural stability, and high antigenicity scores. The predicted combined HLA population coverage of the selected CTL and HTL epitopes was 90.77% across the populations included in the analysis. Immune simulation predicted patterns consistent with humoral and cellular immune activation, including sustained IgG production, elevated IFN-γ and IL-2 secretion, efficient antigen clearance, and generation of immunological memory, whereas molecular docking and molecular dynamics simulations characterized the predicted interaction and conformational behavior of the MEV–TLR1/TLR2 complex. Codon optimization (CAI = 0.996) and in silico cloning into the pET-30a(+) expression vector supported the potential feasibility of recombinant expression in Escherichia coli. Conclusions: In this study, a rationally designed multi-epitope vaccine candidate against diverse S. suis strains was developed using an integrated pangenome-guided reverse vaccinology approach. Based on these computational analyses, the proposed vaccine candidate showed favorable predicted immunogenicity, predicted structural quality, predicted HLA population coverage, and expression feasibility, providing a foundation for future experimental validation and development of a vaccine against diverse S. suis. Full article

Usutu virus is an emerging mosquito-borne flavivirus with an expanding geographic distribution and increasing public health relevance, yet no licensed vaccine is currently available. This study used an integrated reverse vaccinology strategy to identify conserved immunogenic regions from the Envelope protein and NS5 protein, and construct a multi-epitope vaccine. Following sequential computational screening, the retained T-cell and B-cell epitopes satisfied the predefined selection criteria, while selected T-cell epitopes achieved an estimated 96.41% global population coverage. The final vaccine consisted of 240 amino acids and incorporated an adjuvant together with peptide linkers. Computational characterization indicated favorable physicochemical features and a refined three-dimensional model with improved stereochemical characteristics. Receptor-binding analyses predicted favorable interactions with TLR2 and TLR4, producing weighted docking scores of −1326.1 and −1230.2, respectively. Molecular dynamics simulation further characterized the temporal behavior of the vaccine–TLR2 complex, while MM-GBSA analysis yielded an estimated binding energy of −74.78 kcal/mol. C-ImmSim predicted enhanced humoral and cellular immune-response patterns following repeated antigen administration, including increased simulated antibody levels and changes in immune-cell populations. All findings in this study are based on in silico analyses and represent computational predictions rather than experimentally confirmed results. Further experimental validation is required to verify the predicted properties, immunogenicity, and protective potential of the proposed vaccine candidate. Full article

The hepatitis B virus (HBV) remains highly endemic in Sub-Saharan Africa, where perinatal and early childhood transmission contribute substantially to chronic infection. Although routine infant vaccination is widely implemented, the birth-dose coverage remains inconsistent in many settings. This study, carried out in strict compliance with ethical rules, evaluated serological markers of HBV exposure and vaccine-induced immunity among fully vaccinated infants in Cameroon. It was a cross-sectional study involving 9-to-15-month-old infants, fully vaccinated against hepatitis B and HIV negative, living in the towns of Douala and Yaoundé. Infants born to mothers known to be HBsAg-positive were excluded. Their serum samples were tested for HBV serological markers, using lateral flow immunochromatography techniques and indirect ELISA. Whereas 84.85% (56/66) of theses infants achieved seroprotective antiHBs levels, 16.67% (11/66) were antiHBc-seropositive and were all born to antiHBc-seropositive mothers. Overall, 63.64% of these antiHBc-seropositive infants were significantly less likely to demonstrate seroprotection compared with antiHBc-seronegative infants (adjusted OR 30.3; 95% CI 5.58–164.75). These results, highlighting the association between antiHBc positivity and reduced seroprotection, warrant further investigation, including molecular testing to distinguish passive maternal antibody transfer from occult or resolved infection. Strengthening perinatal HBV prevention strategies remains critical to achieving elimination targets. Full article

Despite widespread vaccination programs, pertussis continues to pose a major public health challenge, primarily due to waning immunity, persistent transmission, and treatment delays. This study introduces an SVEITR model to explore the transmission dynamics and control strategies for pertussis. Unlike many existing pertussis models, this framework explicitly incorporates a treatment compartment alongside vaccination and recovery, allowing for a more thorough evaluation of disease control measures. The fundamental mathematical properties of the model are established, equilibrium points are derived, and the basic reproduction number ${\mathcal{R}}_0$ is calculated. Theoretical conditions for local and global stability of the equilibrium points are rigorously analyzed using eigenvalue theory, the Routh–Hurwitz criterion, the Castillo-Chavez methodology, and Lyapunov theory. Bifurcation analysis, conducted via center manifold theory, reveals a forward transcritical bifurcation at ${\mathcal{R}}_0=1$, confirming that disease eradication is possible when ${\mathcal{R}}_0<1$. Local and global sensitivity analyses identify the most influential epidemiological parameters affecting disease dynamics (i.e., transmission, vaccination, and treatment rates). Numerical simulations illustrate the effects of vaccination, transmission, and treatment rates on disease progression and delineate stable and unstable endemic regions. The findings indicate that increased vaccination coverage and prompt treatment significantly reduce disease prevalence, whereas higher transmission rates intensify outbreaks. The proposed model offers new insights into the combined effects of vaccination and treatment in controlling pertussis and provides a quantitative framework for designing effective public health intervention strategies. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory condition that is marked by the growth of lesions outside the uterus, along with angiogenesis, fibrosis, immune dysregulation, and pain sensitization. There is now growing evidence that receptor tyrosine kinase (RTK) signaling networks are central to these processes, integrating proliferative, angiogenic, inflammatory, endocrine, and microenvironmental signals. This review summarizes the roles of six major RTK axes in endometriosis and evaluates their receptor-specific mechanisms, therapeutic relevance, and modulation by representative phytochemicals. An English-language literature search of PubMed was conducted with no publication date restrictions using combinations and variations of the following keywords: phytochemicals, endometriosis, EGFR, VEGFR, IGF1R, PDGFR, FGFR, MET, curcumin, resveratrol, epigallocatechin gallate (EGCG), quercetin, naringenin, berberine, apigenin, luteolin, genistein, and baicalein. Additional search terms related to receptor signaling mechanisms, downstream pathways, cellular phenotypes, and therapeutic relevance were also incorporated to ensure comprehensive coverage of the literature. The RTK signaling pathways control stromal activation, lesion survival, angiogenic support, extracellular matrix remodeling, neuroimmune sensitization, and malignant progression. Of the six RTK axes examined, EGFR, VEGFR, and IGF1R have the strongest mechanistic and pharmacological support, whereas PDGFR, FGFR, and MET remain biologically plausible targets. Even though phytochemicals do not consistently act as receptor-selective RTK inhibitors, evidence shows they reduce RTK-centred signaling networks by targeting common downstream hubs. As a result of their effects at the network level, the phytochemicals may help to suppress lesion proliferation, angiogenesis, invasion, fibrosis, inflammation, oxidative stress, and pain sensitization. Endometriosis should be viewed as an RTK-centered network disease rather than a single-pathway disorder. In this context, phytochemicals act as modulators that attenuate signaling hubs, offering a mechanistically aligned strategy for a disease driven by redundancy and microenvironmental crosstalk. Full article

Background/Objectives: The approval of Abrysvo, a maternal bivalent respiratory syncytial virus (RSV) prefusion F (pre-F) vaccine, marked a major milestone in pediatric prophylaxis. However, real-world serological data on transplacental antibody transfer in Asian populations remains limited. This brief report evaluated serum RSV pre-F immunoglobulin G (IgG) geometric mean titers (GMTs) across three distinct Japanese cohorts. Methods: This single-center, comparative study analyzed neonates born to Abrysvo-vaccinated mothers (n = 12), neonates born to unvaccinated mothers (n = 40), and infants aged <6 months hospitalized with laboratory-confirmed RSV infection (n = 18) using enzyme-linked immunosorbent assay (ELISA). Results: Neonates of vaccinated mothers exhibited significantly higher pre-F IgG GMTs (4.74; 95% CI: 4.30–5.18) than those of unvaccinated mothers (3.80; 95% CI: 3.50–4.14). Conversely, infants requiring hospitalization for RSV infection demonstrated critically low pre-F IgG GMTs (1.08; 95% CI: 0.65–2.15), revealing statistically significant differences across all three groups (p < 0.001). Conclusions: Maternal immunization with Abrysvo significantly enhances passive humoral immunity in Japanese neonates compared to natural background immunity. Given the severe antibody deficiency observed in hospitalized infants, expanding maternal vaccination coverage is a high-priority public health strategy to mitigate the pediatric RSV burden in the post-pandemic era. Full article

Background and Objectives: Despite long-standing MMR vaccination programmes, outbreaks of vaccine-preventable diseases continue to occur worldwide, raising concerns regarding waning immunity and susceptibility gaps in adult populations. Between 2017 and 2019 alone, WHO reported over 880,000 measles cases globally—a fourfold increase over the preceding two years—with outbreaks in both low- and high-income countries despite high childhood vaccination coverage. This study evaluated the seroepidemiology of measles, mumps, and rubella among adults in Türkiye over a nine-year period. Materials and Methods: A retrospective laboratory-based study was conducted using ELISA IgM and IgG results obtained between 2014 and 2022 at a tertiary-care university hospital. Seropositivity rates were analysed by year, age group, and sex. Temporal trends were assessed using the Cochran–Armitage trend test; factors associated with IgG seropositivity were assessed using multivariable logistic regression. Results: Among 10,407 adult test records, overall IgG seropositivity was 75.8% for measles, 94.9% for rubella, and 86.3% for mumps; IgM positivity remained low throughout (0.9%, 0.4%, and 1.9%, respectively). Measles IgG declined significantly from 78.4% in 2014–2019 to 62.6% in 2022 (p < 0.001), whereas Rubella IgG remained stable (93.2–95.7%) and Mumps IgG showed no significant temporal change. Seropositivity increased markedly with age for measles (18–29 years: 70.2% vs. ≥50 years: 93.4%; p < 0.001) and mumps (p = 0.030). Multivariable analysis confirmed that Measles IgG seropositivity was substantially lower in 2022 than in the pooled 2014–2019 period (OR = 0.432, 95% CI: 0.319–0.584, p < 0.001). Rubella seroprotection among women of reproductive age was 94.7% (95% CI: 93.9–95.5%), close to but not statistically distinguishable from the 95% population immunity benchmark used in rubella elimination frameworks. Conclusions: A significant measles immunity gap exists among younger adults in Türkiye, with Measles IgG seropositivity declining from 78.4% in 2014–2019 to 62.6% in 2022, consistent with a cohort effect whereby vaccine-era cohorts exhibit lower protection than older adults with naturally acquired immunity. Rubella immunity, by contrast, remained close to the 95% elimination benchmark throughout. These findings underscore the importance of targeted serological surveillance and evidence-based booster vaccination strategies. Full article

Background: Measles, mumps, and rubella outbreaks continue to occur despite high vaccination coverage, raising concerns about long-term vaccine-induced immunity. This study assessed serological protection against measles, mumps, rubella, and varicella in fully vaccinated Russian adolescents to identify immunity gaps and inform revaccination strategies. Methods: Serum IgG was quantified by commercial ELISA. Analytical cut-offs were: measles ≥ 0.18 IU/mL, rubella ≥ 30 IU/mL, mumps index ≥ 1.0 (index = OD/0.467), and varicella ≥ 1.0 IU/mL; equivocal results were classified as negative in the primary analysis and as positive in a sensitivity analysis. Geometric mean concentrations (GMC) were computed on the natural-logarithm scale. Results: Seropositivity differed markedly between infections (χ² 55.1; p < 0.001): rubella 81.4% (95% CI 74.6–86.7), varicella 57.7% (95% CI 49.8–65.2), mumps 53.2% (95% CI 45.4–60.9) and measles 41.0% (95% CI 33.6–48.9). GMC was lowest for measles (0.132; 95% CI 0.111–0.158) and highest for rubella (61.9; 95% CI 55.3–69.2). The measles estimate was sensitive to the treatment of equivocal results, rising to 53.2% (95% CI 45.4–60.9) at the manufacturer’s cut-off of ≥0.12 IU/mL; rubella rose to 94.9% at ≥16 IU/mL. Conclusions: Lower seropositivity rates for measles and mumps were identified among fully vaccinated adolescents, which fall below standard epidemiological benchmarks. In contrast, rubella seropositivity was robust at 81.4%. Because the measles estimate depended strongly on the assay cut-off applied, and because enzyme immunoassays are known to underestimate seroprevalence relative to neutralization testing, these findings describe the distribution of circulating antibody rather than the prevalence of susceptibility and warrant confirmation in larger representative samples with neutralization testing. Full article

Despite longstanding vaccine availability, human papillomavirus (HPV) remains the most common sexually transmitted infection in the United States and a leading cause of preventable cancers. Additionally, HPV vaccination rates remain below other routinely recommended adolescent immunizations, particularly in rural populations. This study aimed to identify barriers related to healthcare access, socioeconomic conditions, cultural beliefs, and provider–patient communication in rural communities. A bibliographical review of articles published in English from 2020 to 2025 and an analysis of national datasets were conducted to establish trends in HPV vaccination rates. State-level HPV vaccination data for adolescents aged 13–17 years were obtained from America’s Health Rankings and the Centers for Disease Control and Prevention National Immunization Survey-Teen. States were classified as predominantly rural or urban using Rural–Urban Continuum Codes, and mean vaccination completion rates were compared. The mean HPV vaccination completion rate was lower in rural states (60.55%) compared to urban states (67.31%); however, this difference did not meet the selected threshold for statistical significance (p = 0.025). Barriers identified in the literature included reduced access to healthcare, differences in provider communication, socioeconomic constraints, and limited health literacy in rural communities. Of the identified barriers, healthcare provider recommendations emerged as one of the strongest predictors of vaccine acceptance. These findings highlight multilevel determinants contributing to differences in HPV vaccine uptake and underscore the need for targeted, evidence-based strategies to improve vaccine access and coverage in underserved adolescent populations. Full article

Measles remains a public-health concern where immunity gaps and incomplete vaccination coverage persist. This study assessed household and geographic factors associated with laboratory-confirmed measles among suspected cases in three Zambian provinces. A prospective cross-sectional study was conducted during measles outbreaks in five selected districts across Luapula, Northern and Northwestern provinces. Suspected cases meeting the IDSR case definition were consecutively enrolled. Blood samples were collected, transported to the UTH Virology Laboratory, and tested using procured IgG test kits. Participant characteristics were summarised descriptively. Bayesian logistic regression estimated associations between laboratory-confirmed (IgG positive) measles and age, sex, vaccination status, household size and previous measles history, with province added in a second model. Results were reported as posterior odds ratios with 95% credible intervals. Among the 172 suspected cases, 45 (26.2%) were laboratory confirmed (IgG positive). Vaccination status was verified using caregiver-provided immunization cards; status was unknown for 110 (64.0%) participants (all of whom tested negative), reflecting missing vaccination documentation. Vaccinated participants had 93% lower adjusted odds of laboratory-confirmed measles than unvaccinated participants (adjusted posterior OR: 0.07, 95% CrI: 0.02–0.18). Adjusted posterior probabilities were consistently lower among vaccinated participants across all three provinces (34% to 49%) than among unvaccinated participants (86% to 92%). Age, sex and household size were not clearly associated with measles positivity. All four participants reporting a previous measles history tested positive, and the unadjusted association was significant using Fisher’s exact test (p = 0.004). Vaccination status was most strongly associated with laboratory-confirmed measles, with substantially lower adjusted odds among vaccinated participants. These findings reinforce the importance of measles vaccination in outbreak prevention and control. Full article

Adult vaccination is a critical component of preventive healthcare, reducing morbidity and mortality from vaccine-preventable diseases. Despite established recommendations, adult immunisation coverage remains suboptimal, particularly for vaccines beyond influenza and COVID-19. In the United Arab Emirates (UAE), limited evidence exists regarding adult vaccine uptake and determinants influencing immunisation behaviour within its diverse population. Understanding vaccine-specific coverage and associated sociodemographic, healthcare, and workplace factors is essential to guide targeted strategies that strengthen adult immunisation. A cross-sectional study was conducted among 1330 adults aged ≥ 18 years residing in the UAE. Data were collected using a structured self- or interviewer-administered questionnaire assessing uptake of recommended adult vaccines, including COVID-19, influenza, pneumococcal, herpes zoster, Tdap, and HPV. Sociodemographic characteristics, healthcare access, insurance status, workplace factors, and perceived barriers were also assessed. Descriptive statistics summarised vaccination coverage, and associations between uptake and key determinants were examined using SPSS version 30. Statistical significance was defined as p < 0.05. Overall, 71.0% reported receiving at least one adult vaccine. Uptake was highest for COVID-19 (64.9%) and influenza (57.8%), while pneumococcal, herpes zoster, and Tdap coverage remained low (12–13%). HPV uptake was 22.6% among females and 18.9% among males. Higher uptake was observed among females and adults. Social encouragement, insurance coverage, and healthcare access were associated with vaccination, whereas lack of awareness and logistical barriers hindered uptake. Although overall uptake was moderate, significant gaps persist. Integrating vaccination into routine healthcare services and addressing structural and communication barriers are necessary to improve adult vaccination coverage. Full article

Renal cell carcinoma (RCC) comprises molecularly diverse tumor subtypes. This diversity is reflected in distinct and adaptable gene-expression programs that enable tumor cells to reprogram metabolism and survive therapeutic pressure. By regulating RNA processing, export, stability, decay, and translation, messenger RNA (mRNA) modifications may help shape these programs. Examining mRNA modifications is therefore important for understanding metabolic adaptation and treatment resistance in RCC. This narrative review focuses on RCC studies of N6-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), N7-methylguanosine (m⁷G), and N4-acetylcytidine (ac⁴C). We focus on protein-coding transcripts and mRNA-centered mechanisms. Transcript-level studies are most extensive for m⁶A, while selected m⁵C and ac⁴C studies have identified defined regulator–mRNA axes. By comparison, RCC data for specific internal m⁷G sites in mRNA remain largely indirect. Many reported links with immune features or treatment response are based on retrospective analyses rather than treatment-specific clinical validation. Different modification pathways converge on PI3K/AKT, Hippo/YAP, metabolism, and treatment resistance, although direct molecular crosstalk has not been shown in RCC. No RNA-modification biomarker or targeted agent is used in routine RCC care. Further progress will require orthogonal site validation, broader coverage of RCC subtypes, and prospective studies conducted within contemporary treatment settings. Full article

Background/Objectives: Immunization coverage in the Democratic Republic of the Congo (DRC) consistently falls short of global standards, placing the country among those with the highest prevalence of unvaccinated or “zero-dose” children. This study aimed to generate high-resolution (1 km × 1 km) geospatial estimates of coverage for the first to third doses of diphtheria–tetanus–pertussis vaccine (DTP1–3) and the first dose of measles-containing vaccine (MCV1), along with estimates of zero-dose and under-vaccinated children to support vaccination programming in DRC. Methods: We used Bayesian geostatistical modelling to integrate data from the 2023 Enquête de Couverture Vaccinale (ECV) survey with geospatial covariates and harmonized population datasets. The model generated vaccine coverage and dropout rates at 1 × 1 km resolution while accounting for spatial dependence and prediction uncertainty. Grid-level estimates were aggregated to health areas, health zones, and provinces using population-weighted averages, and combined with under-one population estimates to quantify zero-dose and DTP-under-vaccinated children. Results: The grid-level unconstrained coverage estimates (estimation over all land grid squares) showed substantial variability across the country (DTP1: 13.3 to 99.7%; DTP2: 12.3 to 96.8%; DTP3: 3.1 to 93.6%; and MCV1: 7.5 to 93.6%). In total, 56.4% of mapped health areas achieved DTP1 coverage above 80%, but this declined to 32% for DTP2, 15% for DTP3, and 8.3% for MCV1. Around 60.5% of the health zones achieved DTP1 coverage ≥ 80%, while only 2.7% fell below 40%, indicating that substantial disparities persist across these zones. Nationally, based on constrained coverage estimates (only areas with identified built settlements) applied to an estimated 4.2 million children under 1 year in 2024, 18.4% had not received DTP1, 20.7% were DTP-under-vaccinated (received DTP1 but not DTP3), and 46.8% remained unvaccinated for MCV1. Conclusions: The prevalence of large numbers of zero-dose children, together with increased dropout rates, underscores systemic issues in access and follow-up initiatives. These findings are critical for microplanning and targeted outreach to achieve equitable immunization coverage in line with the Immunization Agenda 2030’s goal of leaving no child behind. Full article

Cancer vaccination addresses four distinct problems: preventing oncogenic infection, intercepting premalignant clones, clearing molecular residual disease, and treating established cancer. This hypothesis framework proposes seven sequential gates for antigen-defined, HLA-restricted T-cell vaccines: tumor specificity, natural peptide–HLA presentation, population coverage, persistence under immune selection, selective T-cell recognition, manufacturability, and randomized clinical benefit. The proposed architecture combines a pre-manufactured core of validated shared antigens with a personalized shell when shared targets do not cover the tumor or the patient’s HLA type. Current evidence supports restraint. Individualized mRNA neoantigen therapy with pembrolizumab produced a recurrence-free-survival signal in a randomized phase 2b melanoma trial, whereas a 20-antigen shared cassette produced immunodominant responses toward encoded TP53 epitopes rather than the KRAS neoantigens carried by the tumors. No quantitative coverage or persistence score is presented because the required population frequencies and persistence measurements cannot be supplied reliably from the published record. Four falsifiable predictions define the experiments needed to test presentation-first selection, antigen persistence, escape-route independence, and biomarker-directed treatment. The framework is therefore a research agenda, not a validated decision tool. Full article