In March 2005, the first Phase I clinical trials of a vaccine against the autoimmune disease diabetes mellitus will begin. The protein-based vaccine, developed by teams of researchers at King’s College London and Bristol University (UK), may have the ability to protect insulin-producing pancreatic cells from immune destruction. Currently, more than 72 patients have been recruited to the trial.
Although the exact cause of Type 1 diabetes is unknown, the symptoms arise from the immune destruction of β-pancreatic cells, which are responsible for producing and releasing insulin into the bloodstream to regulate blood sugar levels. Insulin-dependent, or Type 1 diabetes, usually develops before 40 years of age. Patients with this condition require daily insulin injections to prevent their blood sugar levels rising to fatally high levels.
The UK research teams believe they have developed a vaccine that can protect the insulin-producing pancreatic cells from immune destruction. Success with the protein-based vaccine in mice has encouraged the researchers to progress to testing the vaccine in humans.
The first human trials are designed to assess the safety of this new treatment. The researchers hope that the vaccine will not only be able to stop early diabetes before all the pancreatic cells are destroyed, delaying the occurrence of diabetes-related complications, but may also prevent people from developing diabetes in the first place. Colin Dayan (University of Bristol, UK) said, “It will be of help for people who have just been diagnosed. It might stop their insulin-producing cells from deteriorating further. Then, if it proves to be very safe, we would think about using it in people who are at high risk of developing Type 1 diabetes.” The vaccine would need to be administered as early as possible following diagnosis, as 60–85% of β-cells have already been destroyed by the time of diagnosis.
Mark Peakman, a Professor at King’s College London, believes that it may be necessary to combine several different treatment modalities in order to combat a disease such as diabetes. As this disease is on the increase and affects approximately one in 200 individuals in the UK, many scientists are working to cure this condition and there are a number of different treatments being investigated. Another development in the fight against this disease has been in the use of stem cells and organ transplants to restore insulin production.
Georgina Slack, head of research at Diabetes UK, commented, “100 years ago, Type 1 diabetes was a death sentence. We have come a long way in terms of managing the condition. Now we are seeing new approaches in research emerge which are improving the chances of providing a cure. There is no doubt that any breakthroughs would have a huge impact on the treatment of people with diabetes.”
Efficacy results for intranasal flu vaccine
Efficacy trials for FluINsure™, a nonliving intranasally delivered influenza vaccine, have been completed with positive results. Both one and two dose regimens have produced positive safety and immunogenicity data. The vaccine successfully prevented influenza-like illness with a positive influenza virus culture.
The trials were carried out between October 2003 and May 2004 at 28 Canadian sites and involved 1349 healthy subjects 18–64 years of age. The data produced demonstrated a significant increase in serum hemagglutination-inhibiting (HAI) antibody titers for all three vaccine viruses, A/H1N1, A/H3N2 and B, in those who received the vaccine compared with controls. There was no significant difference found for those who received one dose of FluINsure compared with those who received two.
In addition, the results demonstrated that those who received the vaccine experienced a significant increase in salivary secretory immunoglobulin A. Again, there was no difference observed for the different dose regimens.
Safety data from the trials demonstrated there were no significant side effects, such as respiratory or febrile illness, associated with the vaccine at either dosage level compared with the saline placebo. In addition, there was no significant difference in the incidence of adverse events.
Louis F Fries (Vice President, Clinical and Medical Affairs) commented, “These are very encouraging results. In a large field study, we were able to clearly demonstrate both the systemic and mucosal immune responses to the viruses represented in the vaccine. The serum HAI antibody responses to the influenza A viruses induced by FluINsure were quite robust in the context of a mucosal vaccine and while HAI responses to the B component were lower (a frequent finding with B virus antigens in all influenza vaccines), they remained significant.”
Recently, an additional study has been initiated in Canada, to assess the tolerance and strength of immune responses induced by reimmunization with the FluINsure vaccine. ID Biomedical, who initiated the trials, expect to have the first results in spring 2005, with the aim of starting the first pediatric clinical trials of the vaccine at the end of 2005.
Human trials for SARS vaccine
Severe acute respiratory syndrome (SARS) caused worldwide panic when it emerged in China in 2002. The SARS virus rapidly spread, killing 800 people worldwide. However, by 2003 the outbreak had been contained and brought under control by quarantining exposed individuals. Despite the fact that this virus is no longer in the spotlight, public health experts are concerned that another, more serious outbreak could occur due to human contact with infected animals or exposure to virus escaping from laboratory samples.
Gary Nabel, the head of research at the US National Institute of Allergy and Infectious Diseases in Bethesda (MD, USA), commented, “Once a virus like that makes an appearance there is no assurance it will stay dormant.”
Nabel and colleagues have developed a vaccine containing a small piece of DNA extracted from the SARS virus. The researchers plan to initiate trials to test the safety and immunogenicity of the vaccine in humans. The hope is that human cells will take up the DNA and begin to manufacture the SARS protein. In theory, the immune system will identify this protein as foreign and develop the necessary defense to fight a genuine attack with the SARS virus. Murine models have demonstrated that the vaccine is effective at reducing the replication rate of the virus. If proven effective in humans, the vaccine could be stockpiled for use in the event of an outbreak.
Several groups are working on alternative approaches to develop a vaccine effective against SARS, such as injecting the whole killed virus. One such vaccine is already undergoing clinical trials in China, but data is yet to be pruduced. It is not yet known which strategy will be the most effective at preventing this disease.