Experimental reproduction numbers disentangle vaccine effects on susceptibility and infectiousness during H5N1 transmission in geese

Abstract

Vaccination against high pathogenicity avian influenza virus (HPAIV) is increasingly used to protect poultry, but vaccine performance is commonly inferred from clinical protection and virus shedding rather than measured transmission. We asked whether reproduction numbers from controlled transmission experiments can quantify how vaccination changes susceptibility and infectiousness. Domestic geese were prime-boost vaccinated with an H5 clade 2.3.4.4b RNA-replicon vaccine and challenged with homologous HPAIV H5N1. Replicated seeder-sentinel groups represented transmission among unvaccinated animals, to vaccinated contacts, and from vaccinated breakthrough-infected animals. Vaccinated directly challenged geese remained clinically protected although all became RT-qPCR-positive. Estimated reproduction numbers were R0=4.7 (95% CI, 2.8-8.0) among unvaccinated geese, Rs=2.6 (1.6-4.5) for transmission to vaccinated contacts, Ri=3.7 (2.0-6.8) for transmission from vaccinated infected geese, and Rvacc=2.0 (0.8-4.9) for a fully vaccinated population. Vaccination reduced transmission but did not reduce the point estimate for Rvacc below one under these intensive exposure conditions. Vaccinated infected geese also shed substantially less viral RNA, whereas the estimated reduction in infectiousness was more modest, indicating that RNA shedding alone may not reliably predict transmission reduction. Experimental reproduction numbers therefore provide a direct population-level complement to conventional vaccine endpoints and separate effects on susceptibility from effects on onward transmission.