Project Details

Influenza vaccines represent the most effective means of preventing influenza illness, complications, and deaths. Seasonal influenza vaccines are updated most winters because of 'antigenic drift'. Antigenic drift is caused by gene mutations that modify the influenza virus coat. During periods of antigenic drift, past infection with a similar virus, known as 'priming', aids the immune response to seasonal vaccination. Because of priming, the composition of seasonal influenza vaccine is not as critical as for pandemic influenza.

Pandemic influenza occurs because of 'antigenic shift'. Antigenic shift reflects a major change of the virus coat - so the immune system is not 'primed' by infection with a related virus and the population lacks any immunity to the new virus. Accordingly, pandemic vaccine must be more potent than seasonal vaccines. 

The Government has bought two types of pandemic vaccine. One is a whole virus vaccine that is made by growing and killing whole H1N1 influenza virus particles. The other is made by breaking H1N1 virus into non-infectious particles. These particles need a vaccine additive called an 'adjuvant', to boost protection. Both vaccine types work well for H5 bird flu and were safe when tested in thousands of people. They have not been tested against the new H1N1 pandemic virus and have not been tested against each other. It is unclear whether one or two doses are necessary, or whether one vaccine will be better than the other.

The initial availability of vaccine in the UK will be restricted by manufacturing capacity. Supplies will be limited initially, so vaccine must be used as efficiently as possible. There is some evidence that some older people may have been 'primed' by H1N1 infections some years ago. If true, older people may need one dose of vaccine only. 

It is critically important that the Department of Health know whether one or two doses are necessary, how soon protection occurs, and whether there is any reason to give one vaccine in preference to the other. It is not known whether one vaccine would be better than the other should 'antigenic drift' occur. These questions will be addressed in the planned study.

The clinical evaluation will be done by researchers in University teaching hospitals in Leicester, Nottingham, and Sheffield. The laboratory measurements of protection will be done by leading scientists in the UK Health Protection Agency Centre for Infections. The team of investigators is recognised nationally and internationally for their work on the development and assessment of vaccine regimens for pre-pandemic and pandemic vaccines (H1, H5, H7, and H9 subtypes of influenza) and antibody tests to assess them. Members of the team advise the World Health Organisation. The team has been funded for this type of work by the European Union, Department of Health, and the Medical Research Council and has published its findings in the highest quality peer-reviewed medical journals.

Volunteers aged 18 years and older will be given two doses of the earliest available vaccine batches provided by two vaccine manufacturers to the UK Departments of Health.

The clinical trial will be done in 360 men and women, with and without stable medical conditions. The critical early part of the study will extend over a period of 6 weeks after ethical and other regulatory approval are obtained. A final assessment of immunity, and assessment of any long-term adverse events will occur 6 months after the first dose of vaccine. After obtaining signed informed consent, two vaccine doses will be given 21 days apart to volunteers aged 18-44, 45-64, and 65 years and older. Equal numbers in each age group will receive vaccine from each manufacturer, i.e., there will be six groups of 60 people. The number of people in each group follows recommendations on group sizes by the European Medicines Agency Committee for Medicinal Products for Human Use, with allowance for people who do not complete the study. 

Volunteers will be asked to keep a diary of any local or systemic reactions and any other medical events that occur during the study. Blood samples for laboratory measurements of protection will be collected at weekly intervals. We will use criteria for the licensure of seasonal influenza vaccines issued by the Committee for Medicinal Products for Human Use to evaluate the vaccines, and will compare side effects and the levels of protection afforded, for each age group, across all age groups, and by age to the two vaccines. 

The success of vaccination will be judged mainly by the proportion of vaccinees who develop protective levels of antibodies to the pandemic virus.

Funding for this is study is required to support research nurses, medical time, consumables, technical expertise and reagents. .

1. To measure and compare the magnitude of the antibody responses to one and two 0.5mL intramuscular (IM) doses of Baxter and GSK vaccines (i.e., the titres attained and proportion of the population attaining ‘protective’ antibody titres);

2. To examine the kinetics of the antibody responses to vaccination;

3. To measure and compare local and systemic reactions and occurrence of adverse events after each vaccine;
and 

4. If appropriate (i.e., an antigenic drift variant emerges prior to or during the immunisation programme), to evaluate the breadth of the antibody response to the antigenic variant.