Thursday September 29 2011
The primary aim was to test safety not effectiveness
The Daily Telegraph reported that a “vaccine could reduce HIV to ‘minor infection’”. The news story reports on a phase I clinical trial that assessed the safety of a new HIV vaccine in a small group of people in Spain.
The researchers recruited 30 people who did not have HIV and gave 24 of them three injections of the new HIV vaccine, which was based on a smallpox vaccine. The other six people received placebo injections. The researchers followed the volunteers for 48 weeks.
The researchers found that the vaccine appeared to be well-tolerated over this time and there were no serious side effects. More than three-quarters of the volunteers had a detectable immune response to the vaccine. However, the primary aim of this preliminary study was to assess safety not effectiveness. It is not known whether the immune response caused by the vaccine would be sufficient to protect against HIV infection or to lower HIV levels in people who are already HIV positive. It is likely that further safety trials in a larger group of people will be performed before the effectiveness of this vaccine is assessed.
Where did the story come from?
The study was carried out by researchers from The Hospital Clinic-IDIBAPS, Barcelona, Spain, the CentroNacional de Biotecnologia, CSIC, Madrid, Spain and other Spanish, Swedish, Swiss and British research institutions. It was funded by three Spanish research foundations, FIPSE, FIS and HIVACAT.
The study was published in the peer-reviewed medical journal Vaccine.
The research was covered well by The Daily Telegraph, the Daily Mail and the Daily Mirror, which all said that further tests would need to be carried out. The Daily Telegraph detailed what the researchers had said the next steps would be.
What kind of research was this?
This was a phase I clinical trial to assess the safety of an HIV/AIDS vaccine and how well it could provoke an immune response, which is a sign that a vaccine is having an effect. Phase I studies are studies that test the preliminary safety of a treatment in a small group of people. Often these types of studies do not have a control group. In this case, there were 24 people who received the vaccine and six who received a placebo. Importantly, this type of trial is not designed to test effectiveness and the researchers were not trying to assess how well the vaccine would protect people from contracting HIV. However, they did look at how strong the immune response to the vaccine was. Immune response is a marker for eventual success of the vaccine and a sign that the vaccine is having an effect.
The vaccine was based on a smallpox vaccine that had been adapted with HIV genes. The vaccine was called MVA-B. The idea was that the vaccine would prime the body to recognise HIV so that it would mount a rapid immune response. If used to treat people who have already contracted HIV, this would potentially allow the body to clear the HIV to levels that don’t cause disease. If used to prevent people from getting HIV, it would hopefully prevent the virus from entering cells in the first place.
What did the research involve?
The study was carried out in Spain. The researchers recruited 30 men and women who were free from HIV and at low risk of infection. The participants were between 18 and 55 years of age, and 24 were men. The participants had no history of a previous smallpox vaccination. The researchers randomly allocated six people to receive placebo and 24 people to receive the vaccine.
The 24 people received three injections of the vaccine into their muscle, and the control group received placebo injections. Both groups received these injections at the start of the study, after four weeks and after 16 weeks. The participants were then followed for 48 weeks.
The participants were asked to use an effective method of contraception with their partner from 14 days prior to the first vaccination until four months after the last one.
The primary endpoints (the measures considered to be most important by the researchers) were serious side effects and how well the body mounted an immune response. They looked, in particular, at a type of immune cell called a T-cell. The researchers also took into account less severe side effects and how well the body produced antibodies against the vaccine.
Screening for side effects was performed throughout the study. Blood tests were performed at the study start and at weeks four, eight, 16, 20 and 48. The participants were given safe sex counselling and an HIV test at the screening interview and at weeks four, 16 and 48.
What were the basic results?
The researchers said that, overall, the vaccine was well-tolerated. A total of 169 adverse events were reported during follow-up. Five of these were grade-three adverse events, which would be considered serious. However, although the five serious adverse events were all in the vaccination group, these were not considered to be related to the study drug. For example, one volunteer had tonsillitis, one volunteer had a traffic accident, one volunteer had both pneumonia and two asthmatic attacks. Of the 145 reported milder adverse events (grade one and two), 52 were considered to be definitely related to the vaccination. The most common mild adverse events were pain at the site of the injection and headaches.
The researchers found that positive T-cell immune responses were detected in 75% of volunteers and that these were maintained until week 48 in 68% of the participants. The proportion of responders increased after the second dose. Ninety-five per cent of the participants had antibodies against the vaccine at week 18 and 72% had antibodies at week 48.
How did the researchers interpret the results?
The researchers say that in this first phase I trial with the HIV/AIDS vaccine candidate MVA-B in healthy volunteers the vaccine was safe and well-tolerated and elicited strong and durable T-cell responses in 75% of volunteers. They say that their data support further exploration of MVA-B as an HIV vaccine candidate.
This phase I trial showed that this HIV vaccine was well-tolerated and did not lead to serious adverse effects in a small group of healthy volunteers. The vaccine was also shown to cause a T-cell immune response in 75% of the 24 participants and to cause antibody responses in 95%.
These results are encouraging and will probably mean that the researchers go on to look at safety and immune response to this vaccine in a larger group of people. There are two potential ways in which vaccines could be used to fight HIV. A vaccine may either be used as a prophylactic to stop people being infected with the virus, or therapeutically, to help the body to lower HIV levels once a person has already been infected. The aim of therapeutic use would be to reduce disease symptoms.
This study did not look at the effectiveness of the vaccine, including how well it could protect against infection with HIV or lower HIV levels in the body of people already infected.
Further research is needed to test the vaccine in these two areas - preventing HIV infection or reducing the number of virus particles in infected people. Also, other studies are looking at potential HIV vaccines, and research will be needed to test how well this vaccine compares to these.