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Influenza in U.S. High-Risk Populations · Systematic Evidence Curation 2016–2026

Live · 2026-07-09
§ 222 studies
◈ 1523 endpoints
Investigational Prophylactic lens
Vaccine Efficacy Gap

Where current vaccines fail — and Investigational Prophylactic doesn't

Small-multiples of VE by subgroup across seasons. The dashed gold line at 76% shows the Investigational Prophylactic target VE.

Why this page matters
Traditional flu vaccines depend on the recipient's immune response. In immunocompromised adults, that response is blunted — VE drops to 5% in a full order-of-magnitude gap below general adults. Investigational Prophylactic is immune-independent, targeting a flat 76% VE regardless of host immunity. This chart makes the gap literal.
VE in IC
5%
VE ≥65 vs H3N2 (miss)
−3%
VE overall 2025–26
27%
95% CI 21–34
Investigational Prophylactic target VE
76%
Phase 2b readout

VE by Subgroup × Season

Each panel is a subgroup. Points = VE point estimate; ribbons = 95% CI where reported. Gold dashed line = Investigational Prophylactic target 76%.

Immunocompromised
Avg VE 5% · Gap to Investigational Prophylactic: 71 pp
Adults ≥65 (all)
Avg VE 28% · Gap to Investigational Prophylactic: 48 pp
CHF / COPD
Avg VE 28% · Gap to Investigational Prophylactic: 48 pp
ASCVD
Avg VE 24% · Gap to Investigational Prophylactic: 52 pp
General Adults
Avg VE 38% · Gap to Investigational Prophylactic: 38 pp

Immunocompromised is the flattest and lowest line — 5% VE. The gap to 76% Investigational Prophylactic is 15×.

Vaccine Performance Waterfall

General Population → Vaccinated → Protected → Breakthrough → Hospitalization → Death

SubgroupScenario

Same message: current SOC drops the pyramid faster in low-VE subgroups. Investigational Prophylactic restores the drop everywhere.

VE — depth

Absolute vs Relative VE — Enhanced Formulations

How the same estimate reads different ways for HEOR modeling

Relative VE (rVE) is the effect size vs the comparator vaccine. Absolute VE is the effect vs unvaccinated. Both matter for budget impact.

Prior-Season Vaccination Effect

VE among adults ≥65 who were vaccinated in the prior season vs unvaccinated

Repeated vaccination can attenuate current-season VE — the 'antibody landscape' effect. Notably reversed in 2024-25.