LB-016 - EFFECTIVENESS OF HIGH DOSE VERSUS STANDARD DOSE INFLUENZA VACCINES IN OLDER ADULTS : INSIGHTS FROM A MULTI-STRAIN MODELING APPROACH TAKING ANTIGENIC DISTANCE INTO ACCOUNT.

S. Urdy¹, N. Ratto², M. Hanke¹, A. Toledo¹, E. Peyronnet¹, E. Jacob¹, E. Thommes³, S. Chaves⁴, L. Coudeville⁴, J. Boissel¹, L. Bruezière¹, E. Courcelles¹; ¹Novadiscovery, Lyon, France, ²Novadiscovery, Lyon, Rhone-Alpes, France, ³Sanofi, Toronto, Canada, ⁴Sanofi, Lyon, France.

Background: Influenza vaccine effectiveness (VE) varies from season to season and according to the vaccine used. To investigate how antigenic matching and vaccine characteristics impact VE, we developed a mechanistic, knowledge-based mathematical model (ordinary differential equations).

Methods: This model describes within-host dynamics including long-term immunization due to infection with A/H1N1 and A/H3N2 and vaccination with inactivated split vaccines. The calibrated model accounts for cross-reactivity of immune cells elicited during previous infections with new antigens and outputs the seroprotection rates and the proportion of prevented events (PPE, symptomatic/outpatient/inpatient illness) compared to a control arm without vaccine administration.

Results: We simulated the seasonal absolute and relative PPE of high-dose (HD) versus standard dose (SD) in US adults older than 65 years from 2011 to 2022, using as input the antigenic distances between the vaccine and main circulating seasonal strains reported by Nextstrain [1] and associated viral surveillance databases. The predicted PPE falls within confidence intervals reported by the Centers for Disease Control (CDC) in seasons without egg-adaptation [2]. The simulations show that PPE is highly dependent on antigenic matching, especially in hemagglutinin, and that higher dosage improves immunogenicity, activation and memory formation of B cells and CD4 cells.

Conclusion: Across all simulated seasons, the HD vaccine consistently performs better than the SD vaccine, against both subtypes, supporting the use of the HD vaccine in the elderly population [3]. This model could further support research and development of universal vaccines and predict in silico the impact of alternative vaccine strain selection on clinical outcomes in future flu seasons.

[1] Hadfield J. et al. Nextstrain: real-time tracking of pathogen evolution. Bioinformatics, 34(23):4121-4123. doi:10.1093/bioinformatics/bty407 (2018).
[2] https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html Accessed 20 October, 2022.
[3] Lee, J.K.H. et al. Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: An updated systematic review and meta-analysis. Vaccine, 10.1016/j.vaccine.2020.09.004 (2021).