Presentation (CTI)

OBJECTIVES: In June 2024, the US Food and Drug Administration updated its preferred COVID-19 vaccine strain from JN.1 to KP.2. As vaccine technologies differ in the capacity to accommodate strain updates, this decision had implications for mRNA- and protein-based COVID-19 vaccines. 2024/2025 real-world evidence indicated KP.2-adapted mRNA-1273 was 40.7% more effective against COVID-19 hospitalizations than JN.1-adapted NVX-CoV2705; however, the relative contributions of strain selection and vaccine technology remains undetermined. Accordingly, this study explored the public health impact potentially attributable of late strain selection in the United States.
METHODS: A previously published US static COVID-19 public health impact model comparing KP.2-adapted mRNA-1273 and the JN.1-adapted, protein-based NVX-CoV2705 vaccine was used. While the 2024/2025 variants were not explicitly considered, published data on seasonal, country-wide strain-specific absolute VE estimates were used to calculate relative VE decrements between reference and comparison strains and applied as proxy strain-attributable fractions in exploratory analyses. The estimated strain-attributable fractions included 18.3% (JN.1 versus non-JN.1 strains), 30.6% (XEC versus KP.3.1.1), and 51.0% (LP.8.1 versus KP.3.1.1). The observed relative VE of mRNA-1273 compared to NVX-CoV2705 against infection and hospitalization was adjusted using the strain-attributable fractions. Public health impact attributable to strain selection was calculated as the difference between outcomes generated using observed and adjusted VE inputs.
RESULTS: Under observed VE inputs, the KP.2-adapted mRNA-1273 vaccine was projected to avert 1,082,770 symptomatic infections, 52,579 hospitalizations, and 6,859 infection-related deaths relative to the NVX-CoV2705 JN.1-adapted vaccine. Across exploratory scenarios, late strain selection was estimated to account for 224,314-594,529 symptomatic infections (21%-55%); 9,645-26,842 hospitalizations (18%-51%); and 1,258-3,501 infection-related deaths (18%-51%) averted.
CONCLUSIONS: A meaningful proportion of the public health benefit associated with KP.2-adapted vaccination may be attributable to the ability to incorporate late strain selection in June preceding the fall season, highlighting the potential value of accommodating late strain selection.