Uganda: HIV Vaccine a Decade Away

By, New Vision (Kampala), February 20, 2007

A successful HIV vaccine is at least a decade away, the International Aids Vaccine Initiative for Southern Africa (IAVI) said recently.

"A vaccine is at least a decade away. In the event of the Merck vaccine hitting the bar, it will happen earlier," said Dr Wayne Koff, senior vice-president of the IAVI, in Johannesburg, recently.

The Merck vaccine was developed by American company Merck. It is called MRKAd5 and hailed as a "historic milestone in the fight against Aids".

The vaccine will soon enter its final stages of study - trials involving about 3,500 HIV negative male and female volunteers - which will last four years.

MRKAd5 uses the vector Ad5, an element of the vaccine modified by a harmless virus meant to stimulate cellular immune response in the body. Ad5 causes common cold.

An ideal vaccination would be to block HIV early, when it enters the body. A second goal, for which most scientists are aiming, is to control and slow down the progress of the disease, said Koff.

He said the best vaccines are those where weaker forms of the virus are used - called live attenuated vaccines - but this proves difficult with the human immune virus. "This virus is very smart; every time you try to weaken it in the lab, it changes right back to the wild virus it was," Koff added.

IAVI is a global non-profit organisation working to speed up the search for a vaccine to prevent HIV infection and Aids.


Source: http://allafrica.com/stories/200702210466.html

Canada Joins Gates In AIDS Vaccine Fight

By, CBS News, February 22, 2007

(AP) The Canadian government and Bill Gates announced an initiative Tuesday to establish a research institute to develop an AIDS vaccine, committing a total of $119 million to the project. Prime Minister Stephen Harper said his government has pledged $95.3 million to a new fund called the Canadian HIV Vaccine Initiative, while the Bill and Melinda Gates Foundation has promised up to $24 million.

Gates' $33 billion foundation has become a world leader in fighting AIDS and other epidemic diseases as well as extreme poverty, particularly in the developing world.

"Between Canada and the Bill and Melinda Gates Foundation, we will contribute to the effort to develop a safe, effective, affordable and globally accessible HIV vaccine," Harper said alongside Gates in the capital, Ottawa.

"HIV/AIDS is one of the most heart-wrenching health crises the world has ever seen," said Harper. "It is one of the greatest scientific challenges of our time."

The money will help build a new research facility and support Canadian scientists to work with partners around the world. The goal is the manufacture of a preventative vaccine within a decade.

Gates noted that the Canadian initiative would come under the umbrella of the Global HIV Vaccine Enterprise, a global alliance of independent organizations established in 2003 that is dedicated to the development of a preventative HIV vaccine.

"At that time, we recognized that no single company or government alone could take on this challenge, that in fact a number of organizations would need to work together," said the Microsoft co-founder.

The Global HIV Vaccine Enterprise estimates there were nearly 5 million new HIV infections in 2005, and that nearly 40 million people are currently living with HIV/AIDS worldwide.

Gates noted that due to the success of The Global Fund to Fight AIDS, Tuberculosis and Malaria and other partnerships between governments and the private sector, the number of HIV-positive people receiving antiretroviral treatment has gone up to 1.4 million.

"But that still falls very far short of the number of new people being infected each year," he said. "I think scientists would agree that this will be one of the toughest vaccines ever to create, but it therefore needs to be a priority."

AIDS has killed more than 20 million people worldwide, is the leading cause of death in Africa, and the fourth-leading cause of death worldwide.


Source: http://www.cbsnews.com/stories/2007/02/20/world/ap/main2494823.shtml

Vaccines set to target immune panic button

By, Andy Coghlan, newscientistspace, January 27, 2007

A NEW generation of vaccines that exploit natural "alarm bells" in the immune system could be turned against killer diseases such as tuberculosis, malaria and HIV.

To press the panic button, the vaccines use adjuvants - substances that put the immune system on alert, making it more likely to notice the vaccine. Some vaccine injections are already augmented with adjuvant chemicals such as aluminium hydroxide, but the new vaccines have built-in genes for making their own adjuvants.

These adjuvants mobilise the immune system against the particular disease the vaccine targets, making the immune response more focused and potent when the body is infected by the real thing. Vaccines for malaria have already worked in mice, and human trials should start within two years.

The vaccines use harmless viruses that have been engineered to carry genes both for an antigen - a protein from the virus or organism that causes the disease that is being targeted - and for an adjuvant protein.

The virus is seized by antigen-presenting cells (APCs), which are sentinels that patrol the body and apprehend potential attackers before breaking them down and presenting their components to lymphocytes - the white blood cells that are primed by a vaccine to defend the body against the real disease. Once inside an APC, the virus tricks the cell into manufacturing tiny amounts both of the antigen protein and of the adjuvant protein.

Importantly, the adjuvant proteins used by the vaccines press alarm buttons within the cell called RIG-like receptors. This fools the cell into thinking that it has captured a harmful virus, making it more sensitised than usual and therefore more likely to mobilise the rest of the immune system to fight the accompanying antigen protein (see Diagram). This helps train the immune system to fight infection by the disease that carries the antigen in question. "It is the first intracellular adjuvant," says Adrian Hill, head of the team at the University of Oxford that is developing the vaccines.

“The cell is fooled into thinking that it has captured a harmful virus, making it more sensitised than usual”Last week, Hill's team joined forces with British company Cambridge Biostability in a plan to develop such vaccines against the "big three" diseases - malaria, TB and HIV - and to make them storable without refrigeration in poor countries, where they are most needed. The company seals vaccine particles inside tiny sugar spheres that prevent their contents from decaying either over time or in hot climates. The spheres can be stored indefinitely in injectable liquids. Once injected into the bloodstream, the sugars and the liquid break down, releasing the vaccine (New Scientist, 23 October 2004, p 9). "If these vaccines are going to be given, they must be deployable in the developing world and cheap," says Hill.

Bruce Roser, chief scientific adviser of Cambridge Biostability, is confident that Hill's vaccines can be stored "live" within the spheres, as the company has already achieved this with a virus-based measles vaccine.

Marie-Paule Kieny, director of vaccine research at the World Health Organization in Geneva, says that the approach is radical for vaccinology. Genes have been tried as a way to stoke up immunity in cancer therapies, but the idea of equipping vaccines with genes that specifically trigger "alarm" receptors is new. "It is quite complicated," says Kieny, and it may be difficult to fine-tune the vaccine so the immune system doesn't over or under-react to the signals. Using the approach to combat the "big three" is "optimistic, to say the least", she says.


Source: http://space.newscientist.com/article.ns?id=mg19325884.100&feedId=health_rss20

Wealthy nations launch vaccine purchase plan for diseases such as HIV/AIDS, TB, Malaria

By, News-Medical.net, February 13, 2007

Officials from a group of wealthy nations on Friday launched a $1.5 billion plan to provide and develop vaccines for diseases -- including HIV/AIDS, tuberculosis and malaria -- that largely affect developing countries, the New York Times reports (Rosenthal, New York Times, 2/10).

Under the program, donor countries will pledge to buy vaccines that are being developed at a preferential price when they are available. This would create a financial incentive for drug companies to develop vaccines for diseases that largely affect developing countries (Kaiser Daily HIV/AIDS Report, 2/8). Italy, Canada, Norway, Russia and the United Kingdom have committed the funding for the program, which was launched in Rome (New York Times, 2/10). The program, known as the Advance Market Commitment, will phase out its funding after seven to 10 years, and vaccine manufacturers will be required to continue selling their products to developing countries at the discounted price that was established during the process. Vaccines must meet the standards of efficacy, safety and cost-effectiveness laid out by the GAVI Alliance, the World Bank and an assessment committee (Falconi, AP/CP/Globe and Mail, 2/9). According to the GAVI Alliance and the World Bank, the program is expected to prevent the deaths of 5.4 million children by 2030. The first phase of the plan will focus on the pneumococcal vaccine, which prevents pneumonia in children (New York Times, 2/10). World Bank President Paul Wolfowitz, who attended the launch, said the plan's success requires that the vaccines reach patients, are administered effectively and their results are monitored. He added that the international community should help developing countries improve health care infrastructures to increase access to services (Castelfranco, VOA News, 12/9).

Source: http://www.news-medical.net/?id=21866

First Large-Scale HIV Vaccine Trial In South Africa

By, Medical News Today, February 11, 2007

A large-scale clinical trial of a candidate HIV vaccine - which previously showed promise in smaller studies in the United States and elsewhere - has now opened in South Africa. The study plans to enroll up to 3,000 HIV-negative men and women, making it the largest African HIV vaccine trial to date.

Conducted jointly by the South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN), the trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The study vaccine, provided by Merck & Co. Inc. (Whitehouse Station, NJ), contains copies of only three HIV genes, not the entire virus, so it is impossible for a trial volunteer to become infected from the vaccine.

"Our best hope of ending the AIDS epidemic is a safe and effective vaccine," says NIH Director Elias A. Zerhouni, M.D. "To achieve that goal requires the concerted effort of governments, scientists and private industry as well as participation by well-informed volunteers."

"We applaud the South Africans for bringing this important trial to fruition. This international partnership exemplifies the model of collaboration needed to defeat HIV/AIDS," says NIAID Director Anthony S. Fauci, M.D.

In South Africa the trial is called Phambili ("moving forward"). Also known as HVTN 503, it is a Phase IIb "test-of-concept" trial, the first such vaccine study in South Africa. This type of trial is designed to provide preliminary information on vaccine efficacy and thus enable researchers to decide whether or not to conduct a larger Phase III efficacy trial that could lead to licensure.

In smaller trials, the vaccine was found to be safe and to stimulate cellular immune responses against HIV in more than half of volunteers. To date, more than 1,800 people have received at least one injection. Two years ago, the first Phase IIb trial of the vaccine opened at sites in the United States, Canada, South America, Australia and the Caribbean (see http://www3.niaid.nih.gov/news/newsreleases/2005/mercktrial.htm), areas where a subtype of HIV called clade B predominates. That trial is ongoing.

As in that study, the main objectives of HVTN 503 are to determine whether the candidate vaccine can prevent HIV infection or, in those who do become infected, lower the level of HIV early on. Additionally, the new trial will determine if the vaccine, which is based on clade B HIV, has the potential to protect against the HIV clade C subtype prevalent in South Africa. Immune responses in the first several hundred volunteers will be assessed to ensure the vaccine induces promising immune responses in this population against the clade C virus before proceeding to full enrollment.

Study volunteers must be healthy, sexually active, HIV-negative men and women, ages 18 to 35 years old. Investigators will assign them at random to receive either the test vaccine or an inactive placebo injection. The trial is double-blind, meaning that neither the researchers nor the volunteers know which a participant has received. All volunteers will be regularly counseled about ways to reduce their risk of acquiring HIV, and they will be given condoms. Access to care and treatment for sexually transmitted infections will be provided, and because recent findings indicate that medical circumcision can reduce the risk of HIV transmission from women to men, access to medical circumcision will also be provided to male participants who desire it.

In South Africa, the trial is led by Glenda Gray, MBBCH, FCPaeds (SA), of the Perinatal HIV Research Unit, University of the Witwatersrand, based at the Chris Hani Baragwanath Hospital in Soweto. James Kublin, M.D., M.P.H., of Fred Hutchinson Cancer Research Center, Seattle, serves as study co-chair. The study is expected to recruit volunteers at five sites in South Africa, located in Soweto, Cape Town, Klerksdorp, Medunsa and Durban.

According to Dr. Gray, the study team has actively sought community endorsement of and support for this clinical trial, both of which are critical to its success. "Our communities here in South Africa are faced with the burden of HIV on a daily basis, and the trial investigators and study team have spent years developing a rapport with the community so that together we can move forward in our quest to identify improved approaches to prevent new HIV infections."

The test vaccine contains a weakened adenovirus that serves as a carrier for three clade B HIV genes. Adenoviruses are among the main causes of upper respiratory tract ailments such as the common cold. Because the vaccine contains only three HIV genes housed in weakened adenoviruses, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. The study aims to determine if the HIV genes will induce a cellular immune response, producing immune cells that recognize and kill cells infected with HIV.

The South African Medicines Control Council, the South African Department of Agriculture and the U.S. Food and Drug Administration have reviewed the trial and allowed the study to proceed. In order to conduct the trial, sites also are required to obtain institutional ethics and biosafety committee approvals.

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NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

NIAID-Sponsored Vaccine Trial (HVTN 503) in the Republic of South Africa Questions and Answers http://www3.niaid.nih.gov/news/QA/503qa.htm

HIV Vaccine Trials Network (HVTN) http://www.hvtn.org/

South African AIDS Vaccine Initiative (SAAVI) http://www.saavi.org.za/

Contact: NIAID News Office
NIH/National Institute of Allergy and Infectious Diseases


Source: http://www.medicalnewstoday.com/medicalnews.php?newsid=62620&nfid=rssfeeds

Scientists unveil piece of HIV protein that may be key to AIDS vaccine development

By, EurekAlert.org, February 14, 2007

In a finding that could have profound implications for AIDS vaccine design, researchers led by a team at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have generated an atomic-level picture of a key portion of an HIV surface protein as it looks when bound to an infection-fighting antibody. Unlike much of the constantly mutating virus, this protein component is stable and—more importantly, say the researchers—appears vulnerable to attack from this specific antibody, known as b12, that can broadly neutralize HIV.

"Creating an HIV vaccine is one of the great scientific challenges of our time," says NIH Director Elias A. Zerhouni, M.D. "NIH researchers and their colleagues have revealed a gap in HIV's armor and have thereby opened a new avenue to meeting that challenge."

The research team was led by Peter Kwong, Ph.D., of NIAID's Vaccine Research Center (VRC). His collaborators included other scientists from NIAID and the National Cancer Institute, NIH, as well as investigators from the Dana-Farber Cancer Institute, Boston, and The Scripps Research Institute in La Jolla, CA. Their paper appears in the February 15 issue of Nature and is now available online.

"This elegant work by Dr. Kwong and his colleagues provides us with a long-sought picture of the precise interaction between the HIV gp120 surface protein and this neutralizing antibody," says NIAID Director Anthony S. Fauci, M.D. "This finding could help in the development of an HIV vaccine capable of eliciting a robust antibody response."

For years, AIDS vaccine developers have been stymied by the seemingly unlimited ways HIV eludes natural and vaccine-induced immune defenses. Notes Dr. Kwong, "The more we learned about HIV, the more we realized just how many levels of defense the virus has against attacks by the immune system." For example, not only does HIV mutate rapidly and continuously—defeating attempts by the immune system to identify and destroy it—the virus is also swathed by sugary molecules. This nearly impenetrable sugar cloak prevents antibodies from slipping in and blocking the proteins the virus uses to latch onto a cell and infect it.

In 1998, Dr. Kwong and colleagues published the first X-ray snapshot of the core of HIV gp120 as it attaches to a cellular receptor known as CD4. That image gave researchers a glimpse of some sites on the virus that could be targets of drugs or vaccines, but it also revealed the extent of HIV's overlapping defenses. For example, scientists subsequently learned that CD4-gp120 contact causes gp120 to change shape, a viral feint known as conformational masking, which acts to further shield HIV from immune system attack.

While the earlier study provided a picture of the CD4-gp120 complex, the new finding delineates the precise stepwise engagement between gp120 and CD4. The researchers found that the gp120-CD4 encounter starts with a highly focused contact and then expands to a broader surface that stabilizes the interaction.

"The first contact is like a cautious handshake, which then becomes a hearty bear hug," says Gary Nabel, M.D., Ph.D., director of NIAID's VRC and co-author of the new paper.

An effective HIV vaccine likely needs to induce antibodies that can sense and destroy multiple HIV strains. Scientists have sought such broadly neutralizing antibodies by studying the blood of people whose immune systems appear to hold the virus at bay for long periods of time—b12 is one of these rare, broadly neutralizing antibodies.

Until now, no one had succeeded in determining the detailed structure of b12 in complex with gp120. It was extremely difficult to crystallize b12 bound to gp120, says Dr. Kwong, in part due to the inherently flexible nature of the chemical bonds in gp120. To overcome the problem, the investigators created a variety of gp120s and eventually made the protein stiff enough to capture a picture of it in complex with b12. They saw that b12 binds gp120 at the same point where gp120 initially attaches to CD4. Unlike the gp120-CD4 interactions, however, b12 can latch onto the site of CD4's first contact without requiring a shape change in gp120 to create a stable bond between the two molecules. Essentially, the scientists found that the initial point of CD4 contact is a site of gp120 weakness because it is the site of recognition—called an epitope—for b12.

"One of our primary goals is to develop HIV vaccines that can stimulate broadly neutralizing antibodies," says Dr. Nabel. "The structure of this gp120 epitope, and its susceptibility to attack by a broadly neutralizing antibody, shows us a critical area of vulnerability on the virus that we may be able to target with vaccines. This is certainly one of the best leads to come along in recent years."

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For an image of the b12 antibody in contact with a critical target on HIV-1 gp120, see http://www3.niaid.nih.gov/news/newsreleases/2007/b12antibodyimage.htm.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

References: T Zhou et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature DOI: 10.1038/Nature05580 (2007).

PD Kwong et al. Structure of an HIV gp120 envelope glycoprotein in complex with CD4 receptor and a neutralizing human antibody. Nature 393:648-59 (1998).

Vaccine Research Center Structural Biology Laboratory http://www.niaid.nih.gov/vrc/labs_kwong.htm

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.


Source: http://www.eurekalert.org/pub_releases/2007-02/nioa-sup021207.php