Studies of TB vaccines in healthy adults
VOLUNTEER INFORMATION SHEET
From: Dr Helen McShane FRCP PhD, Chief Investigator, TB Vaccine Trials Centre for Clinical Vaccinology & Tropical Medicine (CCVTM) Churchill Hospital, Oxford OX3 7LJ
Tel: 01865 857406 (recruitment co-ordinator)
Fax: 01865 857471
Email: vaccinetrials@well.ox.ac.uk
"A phase I trial to compare the safety and immunogenicity of candidate TB vaccine MVA85A administered by the aerosol inhaled route and the intradermal route in healthy BCG-vaccinated adult subjects.”
Reviewed by Oxfordshire Research Ethics Committee A (reference number 11/SC/0021).
Thank you for showing interest in this clinical trial. Before you decide if you would like to take part, it is important for you to understand why the research is being done and what it would involve. Please take time to read the following information carefully and discuss it with friends, relatives and your GP (General Practitioner) if you wish.
If you are interested in taking part in the study and would like more information please fill in the Registration form below and a member of the study team will contact you.
What is this trial for?
This trial will investigate the administration of a new tuberculosis vaccine, MVA85A, developed at the University of Oxford, to adults by the inhaled route.
Tuberculosis (also known as TB) is a disease which affects more and more people in this country each year and is responsible for more deaths worldwide than any other infectious disease. At present, BCG (Bacille Calmette-Guérin) is the only vaccine against TB. However, it is not always protective. In the last few years we have developed a vaccine that can be given after BCG immunisation in the hope of providing greater protection against TB. This new vaccine is called MVA85A and we have already given it to over 2000 people thus far in our clinical trials conducted in the UK, The Gambia, Senegal, and South Africa.
So far we have been injecting the vaccine intradermally. This means that the vaccine is injected with a tiny needle into the layers of the skin, usually of the upper arm, exactly in the same way as BCG is given. It is generally believed that the skin is a good place to deliver a vaccine because the immune system of the skin is very well developed.
Many vaccines, including those you may have received to protect you against tetanus, hepatitis, and measles, are successfully given intramuscularly. This means that the vaccine is injected into the muscle tissue of the upper arm rather than the skin. We are already conducting a trial to investigate the safety of MVA85A given by the intramuscular route and preliminary results show it is safe.
A third possible route of administration is the inhaled route. This means that an inhaler or nebuliser device is used to turn the vaccine liquid into a very fine mist (aerosol) which can be breathed in (inhaled). Many medicines for asthma, emphysema, and other respiratory diseases are already given in this way, and some vaccines including the measles vaccine have been widely deployed via this route.
We know that the lungs have a very well developed and specialised immune system. We also know that Mycobacterium tuberculosis, the bacterium that causes TB, commonly infects people by being breathed into the lungs, where much of the damage occurs. Additionally the inhaled route of vaccination would remove the need for needles and injections, is easy to perform even by yourself, is well tolerated by adults and children, and is cost effective.
Therefore there is a strong case for administering TB vaccines in this way, and this trial is intended to find out if the inhaled route for administering vaccine MVA85A is at least as safe and immunogenic (effective at stimulating an immune response within the body) as the intradermal route, in people who have previously received BCG. The novel aspect of this trial is that MVA85A is being given to humans by the inhaled route for the first time.
To find out how well the vaccination is working in the lungs, volunteers will undergo a bronchoscopy as part of the trial. As explained below, this is a routine medical procedure performed under light sedation whereby a thin flexible telescope is passed into the lungs to examine them and obtain samples.
What is vaccine MVA85A?
This vaccine is made from a weakened virus that has been altered to contain pieces of DNA (the genetic material found in all living cells) from the bacteria (germs) which cause TB. The virus, called Modified Vaccinia virus Ankara (MVA), has been altered so that it cannot grow in human cells. The piece of DNA added to it is called antigen 85A. This piece of DNA cannot cause TB disease.
Over 2000 individuals have now been safely vaccinated with MVA85A in our clinical trials. These include approximately 1900 individuals (adults, adolescents, children and infants) in The Gambia, Senegal, and South Africa and approximately 150 adults in the UK. In these trials the vaccine has been given with a tiny needle under the skin just like BCG. No serious problems have been reported as a result of the vaccine.
What is a phase I trial?
Vaccine trials in humans are undertaken in three phases, and this trial is a phase I trial. Phase I trials are designed mainly to test the safety of the vaccine, discover the optimal dose or route, and collect some preliminary information on the immune response in a small number of human volunteers. Phase II trials involve the target population and larger numbers and Phase III trials assess whether the vaccine protects against natural infection in a large number of people at risk of infection.
Can I take part?
If you are aged between 18 and 50 years, live in or around Oxford, are in very good health, have been immunised with BCG and have not participated in another clinical trial where MVA vaccines have been used before, you may be eligible to participate. People with respiratory conditions including asthma, and current smokers, may not take part. You must be able to comply with all of the trial requirements (including vaccination, blood tests, and bronchoscopy) and be able to attend all of the follow up visits. Before you can enter the trial you will need to attend a screening visit when a full medical history and examination will be performed.
Participation is voluntary and at the discretion of the investigators, and you are free to withdraw at any time. Women who are pregnant or who are trying to become pregnant should not take part in this trial. Those with a history of allergy to egg or egg products will not be able to participate because the vaccine contains egg proteins.
