HIV breakthrough as scientists discover new vaccine to prevent infection

HIV (Human Immunodeficiency Syndrome) First evidence of possible vaccine as US military-backed medical trial in Thailand cuts HIV infection rate by a third
19 May 2010

A medical trial in Thailand has raised hopes of a major breakthrough in the fight against Aids after scientists said an experimental vaccine had reduced the risk of HIV infection by a third.

A combination of two vaccines was tested on HIV-negative Thai men and women aged 18 to 30 at average risk of becoming infected. All the volunteers were given counselling and condoms to help them avoid HIV. Then half were randomly picked to receive the vaccine, while the other half got dummy shots. Until the trial ended, nobody knew who had been given the genuine vaccine and who had not a relatively small number of people became infected with HIV 51 of the 8,197 people given the vaccine, and 74 of the 8,198 who received dummy shots but the difference was statistically significant, which means scientists believe it could not have happened by chance. It worked out at a 31% lower risk of infection for the vaccine group.

Colonel Jerome Kim, who helped to lead the $105m (64m) study for the US army, said it was "the first evidence that we could have a safe and effective preventive vaccine". "It gives me cautious optimism about the possibility of improving this result," he said. "This is something that we can do." Every day, 7,000 people worldwide are newly infected with HIV; 2 million died of Aids in 2007, the UN agency Unaids estimates. The Aids Vaccine Advocacy Coalition, an international group that has worked towards developing a vaccine, welcomed the results of the trial the third major study since 1983, when HIV was identified as the cause of Aids as "a historic milestone".

The executive director, Mitchell Warren, said: "There is little doubt that this finding will energise and redirect the Aids vaccine field." Frances Gotch, professor of immunology at Imperial College London, said the results appeared to be statistically significant and may have been the effect of the two different vaccines working in tandem to more powerful effect. "The fact that they have seen a response with people with such a low incidence of infection is impressive," Gotch, who is also the principal investigator for the International Aids Vaccine Initiative, told the Guardian. "Of course it's not 100% of people [protected] but 31% could make an enormous difference in the world. I think this is something we can work with." Thailand's ministry of public health conducted the study, which used strains of HIV common in Thailand. Scientists stressed it was not known whether such a vaccine would work against other strains elsewhere in the world. The study was done in Thailand because US army scientists carried out pivotal research in that country when the Aids epidemic emerged there, isolating virus strains and providing genetic information on them to vaccine makers.

The study tested a two-vaccine combination in a "prime-boost" approach, where the first one primes the immune system to attack the HIV virus, and the second one strengthens the response. Alvac uses canarypox, a bird virus, altered so it can't cause human disease, to ferry synthetic versions of three HIV genes into the body. AidsVax contains a genetically engineered version of a protein on HIV's surface. It is unclear whether vaccine makers will seek to license the two-vaccine combination in Thailand. Before the trial began, the US Food and Drug Administration said other studies would be needed before the vaccine could be considered for US licensing. The full results of the trial will be presented at an international Aids vaccine conference in Paris in October.

The executive director of the Global HIV Vaccine Enterprise, an alliance of research bodies and funders like the Gates Foundation, said the results showed a vaccine was an achievable goal. "This is a historic day in the 26-year quest to develop an Aids vaccine," said Dr Alan Bernstein. "This trial is the first demonstration in humans that, with more research, it will be possible to develop a vaccine that is fully protective against HIV." Deborah Jack, chief executive of the National Aids Trust in the UK, said a vaccine, by far the most effective way of tackling serious infectious diseases, was desperately needed. More work was needed, but the promising findings "justify the continuing investments and efforts of the international community, including the UK government, to develop a vaccine." The Terrence Higgins Trust said it was treating the results with "cautious optimism". "This is the first step on a very long road," said the policy manager, Vicky Sheard. "There's a lot of research needed into how a vaccine can be rolled out, how costly it's going to be, whether it's going to be effective against different strains."

Source

http://www.guardian.co.uk/world/2009/sep/24/hiv-infection-vaccine-aids-breakthrough

Leukemia Vaccine Under Development in the UK

By BiotechDaily International staff writers
Posted on 05 Feb 2010

British scientists have developed a vaccine treatment for leukemia that can be used to stop the disease returning after chemotherapy or bone marrow transplant. The vaccine is due to be assessed on patients for the first time. Eventually, it is hoped the drug, which activates the body’s own immune system against the leukemia, could be used to treat other types of cancers. Treatment for leukemia comes in two stages--chemotherapy to rid the body of the disease, then to prevent it returning either further chemotherapy or a bone marrow transplant. Latest survival rates reveal that more than half the people with leukemia die within five years of diagnosis.

The first patients to be treated as part of the clinical trial at Kings College Hospital (London, UK) have the form of the disease known as acute myeloid leukemia (AML), the most common form in adults. Even with aggressive treatment, half would typically find the disease returns. In the initial stages of the trial patients will be enrolled in the trial if they have had chemotherapy and a bone marrow transplant. If early trials are successful, the vaccine may be tested in patients who cannot have a bone marrow transplant because they are unsuitable or a match cannot be found. The study led by Prof. Ghulam Mufti, Prof. Farzin Farzaneh, and Dr. Nicola Hardwick has involved comprehensive work to develop a synthetic virus, which carries the two genes into the immune system. Farzin Farzaneh, professor of molecular medicine, in the department of hematooncology at the College, reported that if the trials are successful then the vaccine could be rolled out to treat other leukemias and cancers. It is the same concept as normal vaccines. The immune system is made to see something as foreign and can then destroy it itself. This has the chance to be curative.

The hypothesis behind cancer vaccines is not necessarily to prevent the disease. Instead, once a patient has been diagnosed, the vaccine programs the immune system to search for cancer cells and destroy them. The vaccine then triggers the immune system to recognize leukemia cells if they return, which prevents a relapse of the disease. The vaccine is created by removing cells from the patient's blood and manipulating them in the laboratory. The cells are given two genes that act as flags to help identify the leukemia. It effectively focuses and boosts the immune systems ability to seek out and destroy cancer cells. The research is to be published in an upcoming issue of Cancer Immunology Immunotherapy. The study follows successful experiments on experimental tumor models demonstrating that injection with the gene modified tumor cells results in the induction of immune mediated tumor rejection. The research was carried out at King's College London's Experimental Cancer Medicine Centre (ECMC), which is one of 17 new centers across the United Kingdom launched to develop basic science into treatments for patients as quickly as possible.

Source

http://biotechdaily.com/therapeutics/articles/294727818/leukemia_vaccine_under_development_in_the_uk.html

Lung cancer vaccine under development:

Results are encouraging
By William J. Cromie
Gazette Staff

Medical investigators have begun to see some light at the end of a long tunnel that may lead to a vaccine against lung cancer. A trial vaccine given to 25 patients in advanced stages of the disease has produced what researchers call "encouraging results." Lung cancer is the leading cause of cancer deaths in North America and Europe. More people die of it than of breast, prostate, and colon cancer combined. The vaccine is therapeutic rather than preventive, designed to allow patients to live longer, not to prevent the disease

"Lung cancer is so hard to deal with because, in most patients, it has already spread beyond the lungs before it is detected," says Glenn Dranoff, associate professor of medicine at the Harvard Medical School. "Most of these people don't live longer than a year." Eighteen of the 25 patients who received the vaccine showed signs that it stimulated their body's natural immune system to mount a heightened attack against the tumors. Three of the survivors are still alive as long as 43 months after receiving treatment.

Pieces of tumor recovered from six patients showed that, in three of them, immune-system proteins penetrated into the tumors and killed many of their cells. That kind of result is heartening considering that prior surgery and chemotherapy had severely weakened the natural protection given by their own immune systems. No toxic side effects occurred in any of the patients. These experiments were not done to effect a cure, but, as required by the Food and Drug Administration, to test the vaccine's safety. It passed with a high grade. The experimenters, who work at the Dana-Farber Cancer Institute and several other Harvard-affiliated hospitals in Boston, reported their results in the Feb. 15 issue of the Journal of Clinical Oncology.

Dranoff, who led the team, says he is not aware of any other academia group working on this type of lung-cancer vaccine. He and other team members originally developed it to treat patients with advanced melanoma, a skin cancer that becomes lethal if allowed to spread. "The vaccine has also passed safety trials for melanoma," Dranoff says, "and we have begun testing it on ovarian cancer and leukemia patients."

Custom-tailored vaccines

The next step is to carry out trials of the vaccine with patients in earlier stages of lung cancer and melanoma. "When found before they spread, lung tumors can be removed by surgery, but nothing we know of prevents them from reappearing," Dranoff explains. "Once the tumors spread, we treat people with chemotherapy. That makes them feel better for a short time, then the drugs become ineffective. Our goal is to evaluate the vaccine on patients who have localized tumors removed by surgery. If we can prevent their malignancy from reappearing and spreading, then the vaccine would be a success."

Rather than a one-fits-all generic vaccine, Dranoff's team uses a custom-tailored approach. Part of a lung tumor is removed, then a gene that produces an immune-stimulating protein is inserted into a harmless virus and the combination put back into the patient. The protein, known as GM-CSF (granulocyte-macrophage colony-stimulating factor), kick starts an immune reaction against the tumor cells. In 18 of 25 patients (72 percent), evidence indicates that such a customized vaccine initiated an immune attack on the tumors, and did so without any harmful side effects. This approach worked the same way in melanoma patients. "That's quite encouraging," Dranoff says. "It tells us we're on track to understanding how the immune system responds to tumor cells and how we can use that information for treatment." In other words, they're on track to reach the end of the tunnel.

But the tunnel is dark and not without other obstacles. Vaccines against foreign invaders initiate potent attacks on foreign viruses and bacteria, but tumors are not that foreign; they're part of the "self." Once initiated, an immune attack needs reinforcement. "We're now studying ways to increase the magnitude of the immune response after its initiation," Dranoff says. "The result will probably be multiple forms of immune treatment to make the vaccine more effective." Tests with patients in earlier stages of lung cancer and melanoma will involve many more people at different places around the country. Such Phase II trials, as they are known, are logistically impossible for most academic research labs to do. Pharmaceutical or biotechnology companies often join the effort at this point. Cell Gensys, a company in Fulton City, Calif., has begun such tests on the lung cancer vaccine. The company also has started Phase II trials with a prostate cancer vaccine that uses GM-CSF.

Learning from tumors

Meanwhile, Dranoff and his colleagues study the patients and tumors that had the best responses to their vaccine. This is more difficult to do with lung tumors than with more easily accessible skin malignancies. That's why the customized approach was started with melanoma in the first place. After successful experiments with animals, Dranoff and Richard Mulligan, now Mallinckrodt Professor of Genetics at Harvard Medical School, began working with melanoma patients in 1994. It was 1997 before they felt they knew enough to try the vaccine on lung tumors. The many colleagues they worked with on developing the first lung vaccine include Ravi Salgia of the Dana-Farber Cancer Institute and Thomas Lynch of Massachusetts General Hospital.

The work ahead involves closely studying the tumors that showed the best response to the lung cancer vaccine, then comparing them with those that showed the least beneficial effects. The results should shed more light into the parts of tunnel ahead. The eventual goal is to develop a vaccine that will not just add more years to the lives of lung cancer and other cancer patients but will prevent these diseases from developing in the first place. In the meantime, Dranoff notes, "We have long-term survivors from the lung and melanoma trials, and we're learning lots of important things from them."

Source

http://www.news.harvard.edu/gazette/2003/03.13/01-vaccine.html