Pre-clinical Development of an Adenovirus Vectored Universal Influenza Vaccine

Lead Research Organisation: University of Oxford
Department Name: Medical Sciences Division

Abstract

A vaccine that could provide lasting immunity to all influenza A viruses could change the way we vaccinate against flu by enabling vaccination of the whole population and would provide protection against new subtypes that could potentially cause a new pandemic. In this project we will create an adenoviruse-vectored universal flu vaccine, and prepare for clinical trials of this new vaccine.

Technical Summary

A vaccine against influenza that induced protective T cell responses against conserved internal antigens could provide lasting immunity against not only human seasonal ?flu (H1N1 or H3N2 subtypes), but also other subtypes currently found in avian species or swine which threaten to cause a new ?flu pandemic. Adenoviruses are the ideal vector for such a vaccine as they induce broad, potent T cell responses after a single vaccination, so could be used in children to confer broad immunity rapidly. They can also boost pre-existing T cell responses acquired by prior exposure to ?flu that have since declined to non-protective levels. We propose to construct a replication-deficient adenovirus vectored vaccine expressing conserved influenza antigens, complete pre-clinical evaluation, GMP manufacture and regulatory and ethical submissions to prepare for a phase I trial of this vaccine.
 
Description MRC DPFS_DCS
Amount £793,586 (GBP)
Funding ID MR/N006372/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2016 
End 02/2018
 
Title Simian adenovirus and hybrid adenoviral vectors 
Description The invention covers recombinant adenoviral vectors derived from simian adenovirus Y25. The viral vector is known as ChAdOx1. 
IP Reference WO2012172277 
Protection Patent granted
Year Protection Granted 2017
Licensed Yes
Impact The use of the ChAdOx1 -vectored influenza vaccine has been licensed to a new spinout company from the University of Oxford with funding form Oxford Science Investments. The company has been formed around two viral vector vaccines, one to prevent influenza and the other to treat prostate cancer. Viral vector vaccines are particularly good at treating some of the most recalcitrant illnesses. The underlying technology is built on years of experience perfecting viral vector vaccine technology across multiple indications. The company's protected chimpanzee adenovirus technology is the best way to generate T-cell responses and thereby generate lasting cell-mediated immunity. The assets are already in the clinic with very promising initial results. The founders of the company are Professor Adrian Hill (Director of the Jenner Institute) and Professor Sarah Gilbert (Lead in influenza and MERS), who combine their exceptional scientific skills with regulatory and manufacturing experience. This autumn, Vaccitech will begin a phase IIB efficacy study for a universal influenza vaccine in the over 65 population, and an extended phase I prostate cancer trial.
 
Title ChAdOx1-NP+M1 
Description Novel adenovirus-vectored influenza vaccine designed to boost protective cross-reactive T cell responses. I have now ben awarded a further MRC DPFS-DCS grant to continue clinical assessment of this novel vaccine. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Under active development/distribution
Clinical Trial? Yes
Impact cGMP manufacturing of this product is now complete, and QC testing is underway. Unlike the initial product that the project started with (PanAd3-NP+M1) yields were high enough to allow for vaccine manufacturing. This new influenza vaccine has now entered clinical testing in a dose escalation study. This was completed with no safety issues, and good immunogenicity was demonstrated. Applications are now being prepared for further Phase I testing, having now established the dose to be used in future studies.This novel vaccine could potentially play a major rolet on reducing the impact of influenza. 
URL http://clinicaltrials.gov/show/NCT01623518
 
Company Name Vaccitech 
Description Vaccitech will develop viral-vectored vaccines originally produced at the University of Oxford, with a focus an influenza and therapeutic vaccines against prostate cancer. 
Year Established 2016 
Impact Nothing yet - the investment was finalised three days ago.