An Optimised Live Attenuated Influenza Vaccine Ferret Efficacy Model Successfully Translates H1N1 Clinical Data

Overview

Journal Vaccines (Basel)

Date 2024 Nov 26

PMID 39591178

Authors

Katarzyna E Schewe

Shaun Cooper

Jonathan Crowe

Steffan Llewellyn

Lydia Ritter

Kathryn A Ryan

Oliver Dibben

Affiliations

Soon will be listed here.

Abstract

Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype () strains, were unable to predict these fluctuations. By optimising the vaccine dose and utilising clinically relevant endpoints, we aimed to develop a ferret efficacy model able to reproduce clinical observations. Ferrets were intranasally vaccinated with 4 Log FFU/animal (1000-fold reduction compared to clinical dose) of seven historical LAIV formulations with known (19-90%) H1N1 vaccine efficacy or effectiveness (VE). Following homologous H1N1 virus challenge, protection was assessed based on primary endpoints of virus shedding in the upper respiratory tract and the development of fever. LAIV formulations with high (82-90%) H1N1 VE provided significant protection from challenge, while formulations with reduced (19-32%) VE tended not to provide significant protection. The strongest correlation observed was between reduction in shedding and VE (R = 0.75). Conversely, serum immunogenicity following vaccination was not a reliable indicator of protection (R = 0.37). This demonstrated that, by optimisation of the vaccine dose and the use of non-serological, clinically relevant protection endpoints, the ferret model could successfully translate clinical H1N1 LAIV VE data.

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