Human Influenza Vaccine Programme

Programme Leader: Prof Sarah Gilbert

Major antigens of the Influenza virus
Major antigens of the Influenza virus

 

Background

Current vaccines against seasonal or pandemic influenza work by inducing antibodies to highly variable surface proteins of influenza.

The vaccines have to be reformulated each year to take account of antigenic drift and shift.

Information on the viruses to be included in the vaccine is only available a few months before the vaccine is required for use, so that manufacturers have a limited time to produce the vaccine. If delays in the process occur there will be shortages of vaccine for that year.

Aim: A universal flu vaccine

At the Jenner Institute we are working on an entirely different approach to influenza vaccination, based on T cell immunity to the highly conserved internal antigens of influenza. We aim to generate a vaccine suitable for use in all ages, providing protection against currently circulating seasonal influenza as well as avian subtypes that may in future gain the ability to transmit between humans and bring about a new pandemic.

Clinical trials

Clinical trials of Modified Vaccinia virus Ankara expressing conserved influenza antigens (MVA-NP+M1) began in Oxford in 2008. The first trial assessed safety and immunogenicity of the vaccine at different doses and this has now been published (Berthoud et al., 2011). Following positive results in that study, we went on to conduct an influenza challenge study in which half of the volunteers were vaccinated, half were not, and all were subsequently infected with influenza to test if the vaccine protected them. There was a significant reduction in duration of virus shedding in the vaccinated volunteers, and fewer vaccinated than non-vaccinated volunteers developed laboratory-confirmed influenza (Lillie et al., 2012).

Another trial tested the effect of giving MVA-NP+M1 at the same time as a licensed influenza vaccine, trivalent inactivated vaccine (TIV). Pre-clinical studies have shown that as well as boosting T cells recognising the influenza antigens included in the vaccine, antibody responses to TIV were also increased. This could be an easily deployable solution to improving the immunogenicity of TIV in older adults, and results from this trial will be available during 2012.

A new vaccine using a simian adenovirus vector developed in Oxford to express conserved influenza antigens is also being developed and the first clinical study with this new vaccine has now started.

Group Members

Prof Sarah Gilbert, Programme Leader

Dr Pedro Folegatti, Clinical Research Fellow 

Assoc. Prof Teresa Lambe, Senior Pre-Clinical Immunologist

Assoc. Prof Katie Ewer, Senior Immunologist

Dr Amy Flaxman, Post-doctoral scientist

Dr Amy Boyd, Project manager

Duncan Bellamy, Research assistant

Nicola Manning, PhD student, joint with The Pirbright Institute

Publications

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

Rapid development of vaccines against emerging pathogens: The replication-deficient simian adenovirus platform technology.

Potent CD81 T-Cell Immunogenicity in Humans of a Novel Heterosubtypic Influenza A Vaccine, MVA-NP+M1

Preliminary Assessment of the Efficacy of a T-Cell–Based Influenza Vaccine, MVA-NP+M1, in Humans

T-Cell Responses in Children to Internal Influenza Antigens, 1 Year After Immunization With Pandemic H1N1 Influenza Vaccine, and Response to Revaccination With Seasonal Trivalent-inactivated Influenza Vaccine.