DAN-RSV Vaccine Efficacy Data: Resolving the Illusion of Second-Season Protection Loss via Transmission Modelling (Short: DAN-RSV VE Data: Illusion of Protection Loss via Transmission Modelling)

Title: Institutional Interventions and the Inferiority Test Design (The Pohl Hypothesis) in Respiratory Syncytial Virus (RSV) Vaccination Program Evaluation

DAN-RSV Vaccine Efficacy Data: Resolving the Illusion of Second-Season Protection Loss via Transmission Modelling

DAN-RSV vaccine efficacy (VE) data (1) create an epidemiological distortion by underestimating baseline infection-acquired immunity (2). While unselected mass-ITT second-year VE averages collapse to 56.2% (1), a dynamic cohort reconstruction reveals a stable second-season tissue-level VE of 74.76%, demonstrating no rapid biological failure. Recalculation background stems from a longitudinal observational highly vulnerable patient group tracking with a 0.74%–0.77% baseline insufficiently pre-immunized threshold (2, 3). Utilizing a worldwide valid 0.04% mechanical ventilation anchor isolates a true Infection-Hospitalization Rate (IHR₁) of 0.870345% for naive tissue. In season one (2024/2025), the real-world transmission pressure caused a 3.15103% attack rate across the arms, resulting in 18 versus 3 hospitalizations within the 486 insufficiently pre-immunized individuals per cohort (true fresh VE of 83.33%). In season two, natural immunity shifts the denominators; incorporating a precise biological protective decay influx (+54.16) generates an active control denominator of 530 vulnerable individuals, causing 17 hospitalizations under a seasonal attack rate of 3.20943%. Crucially, sterile vaccine protection lacks multi-epitope memory building; driven by rapid antibody waning, the vaccinated vulnerability pool artificially inflated to 1,044 individuals, triggering 7 real-world hospitalizations. By separating the 2.71 expected baseline failures from these 7 observed outcomes, I isolate exactly 4.29 excess waning-driven admissions, proving that pure quantitative antibody decay accounts for exactly 25.24% of the observed disease burden relative to the 17 unmedicated control cases, while tissue-level protection mediated by cellular memory remains robustly intact at a true biologically adjusted second-season efficacy of exactly 74.76% (1 − 4.29 / 17). Integrating biomarker-guided pre-vaccination screening ("Screen Before You Inject") in routine public health mandates is urgently required to eliminate this structural allocation blindness (3).

References:

1. Dynamic Cohort Study Group. Durability of RSV Prefusion F Vaccine Protection across Two RSV Seasons. NEJM Evid. 2026;5(3). doi.org
2. Pohl C. Baseline Immunity and its Natural Course against Respiratory Syncytial Virus (RSV) in Rheumatic Patients while starting Vaccination Program-Medical and Economic Critical Insights by using a New Inferiority Design Principle. Ann Rheum Dis 2026;85(suppl 1):POS0032. doi:10.1136/annrheumdis-2026-eular.B.3586.
3. Pohl C. Respiratory Syncytial Virus (RSV) Vaccination Program – Mass Vaccination Strategy versus Precise Medicine Model as Economic Burden. Zenodo. July 5, 2026. [Preprint]. DOI:10.5281/zenodo.21207877.

Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process:

During the preparation of this work, the author used OpenAI's Large Language Model to support the linguistic polishing, grammatical refinement, and bibliographical formatting of the manuscript. The author reviewed and edited the output as needed and takes full responsibility for the content of the published article.

The author declares no competing financial or professional interests and confirms that this manuscript is original and has not been published previously.