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RV144 HIV Vaccine Trial
Thai or English version Thai version English version Download PDFDownload Press Release RV144 HIV Vaccine Trial in PDF

Follow-up Studies to the RV144 HIV Vaccine Trial Provide Possible Explanation for How the Vaccine May Have Protected Against HIV

MHRP logo AFRIMS MHRP MOPH-TAVEG RV144 POC
RV144 HIV Vaccine Trial

April 5, 2012 (Silver Spring, Md.)—Researchers have discovered important clues about the immune responses that may have played a role in protecting some volunteers from HIV in the RV144 Thai trial. Results from extensive RV144 laboratory studies were published today in the online version of the New England Journal of Medicine.

The RV144 study in Thailand was the first HIV vaccine trial to show some effectiveness in preventing HIV infection. “These studies reinforce and extend the results seen in the RV144 trial and provide new insights that may lead to a better and longer-lasting HIV vaccine,” noted Col. Jerome Kim of the U.S. Military HIV Research Program (MHRP) and senior author of the study.

Walter Reed Army Institute of Research and Duke University researchers collaborated with more than 25 institutions to analyze immune responses elicited in vaccine recipients. The researchers found that different types of antibody responses were associated with a higher or lower rate of HIV infection. 

Barton Haynes, M.D., at Duke University led the studies. “This unprecedented collaboration brought together investigators from all over the world to compare immune function tests to understand the outcome of the RV144 trial. By studying those who became infected compared to those who did not, we believe we have found very important clues for how the RV144 vaccine regimen might have worked,” said Haynes.

The first finding is that antibodies (IgG) specific to a particular region (called V2) of the HIV outer coat (envelope protein) correlated with lower infection rates among those who were vaccinated. The hypothesis is that when IgG antibodies bind to the V2 region, they might help prevent infection.

A second finding in the RV144 laboratory studies indicates that vaccine recipients with the highest blood levels of a different type of envelope binding antibody (IgA) appeared to have less protection from HIV than those with low levels. Scientists hypothesize that these IgA antibodies to a different region of HIV envelope may have interfered with possible vaccine-induced protective responses.

Results from RV144, a clinical trial involving more than 16,000 adult volunteers in Thailand, were published in the New England Journal of Medicine in 20091. The results showed that the prime-boost combination of ALVAC® HIV and AIDSVAX® B/E was safe and lowered the rate of HIV infection by an estimated 31.2% compared with placebo (p=0.04). These data provided the first evidence in humans that a safe and effective preventive HIV vaccine is possible, and provided an opportunity to look for vaccine-induced immune responses that correlated with the rate of infection.

These laboratory studies inform new testable hypotheses that, if validated, may help scientists prioritize vaccine candidates for future clinical trials, potentially accelerating the development of a more efficacious vaccine. Col. Nelson Michael, MHRP Director and co-author of the study noted, “Different HIV vaccines may protect against HIV in different ways. More research is needed to fully understand these results, and to determine if they can be generalized to other types of HIV vaccines or similar vaccines tested against other regional types of HIV or via different routes of exposure.”

The RV144 laboratory research was initiated and coordinated by the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, which receives funding from The U.S. Army Medical Research and Materiel Command and the Division of AIDS, NIAID, NIH. These studies were conducted by a large international collaboration led by the Center for HIV/AIDS Vaccine Immunology (CHAVI), which Dr. Haynes directs and is funded by the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), and by the Collaboration for AIDS Vaccine Discovery, which is funded by the Bill & Melinda Gates Foundation. The Statistical Center for HIV/AIDS Research and Prevention (SCHARP) at the Fred Hutchinson Cancer Research Center conducted the statistical design and analyses.

# # #

Articles:
B. Haynes et al., Immune Correlates Analysis of the ALVAC-AIDSVAX HIV-1 Vaccine Efficacy Trial. N Engl J Med 2012     
1 S. Rerks-Ngarm et al., Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. N Engl J Med 2009; 361:2209-2220

 

About MHRP:
The US Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research conducts research to develop an effective HIV vaccine and integrates prevention, treatment, diagnosis and monitoring as part of a global effort to protect troops and reduce the impact of HIV worldwide. MHRP has developed five state-of-the-art international research sites in the U.S., Africa and Asia. The program successfully collaborates on HIV prevention care and treatment services, funded by the President’s Emergency Plan for AIDS Relief (PEPFAR), with African militaries and in the communities where it conducts research.

For more information, visit www.hivresearch.org

 


Source from BBC News


16 November 2010 Last updated at 00:04 GMT

Malaria vaccine: Inside look at first human trial

Go to BBC News page to read the full article and watch this VDO clip
Nick van Gorden explains why he chose to be bitten by infected mosquitoes

The first clinical trial for a vaccine against the most widespread strain of malaria, Plasmodium vivax, is now under way at the Walter Reed Army Institute for Research (WRAIR), near Washington DC. The BBC's Jane O'Brien speaks with those heading the trial and individuals who are being bitten by infected mosquitoes to help further the research.

US army medic Joseph Civitello admits that becoming deliberately infected with malaria - one of the world's deadliest diseases - is "definitely nuts".

But without such volunteers, it would be almost impossible to test a new vaccine aimed at protecting the military overseas and preventing some of the estimated 300 million cases of malaria that occur every year.

First Sgt Civitello is part of the world's first clinical trial of a vaccine against Plasmodium vivax - the most widespread strain of malaria.

It's not as deadly as Plasmodium falciparum, which is endemic in Africa and kills millions of people, but it can resurface years after infection and still make its victims extremely ill.

"It was weird because I did this knowing I was going to get sick," says Sgt Civitello.

"Fortunately I'm in a hotel room with doctors and nurses nearby and not out in the woods somewhere."

Unlike most of the other volunteers in this unique trial, Sgt Civitello wasn't given the test vaccine.

Human test subjects

He's part of a small control group - a human yardstick - needed by doctors to confirm that all the study participants have been infected.

Mosquitoes infected with the Plasmodium vivax strain are fed blood

And as predicted, about 10 days after being bitten by mosquitoes in a laboratory, he displayed all the symptoms of malaria.

"It started out with a headache, then a general malaise throughout the day. My eyeballs hurt, and I was really sensitive to cold and hot - my skin was sensitive and I had sweats and chills all night long. It was like extremely bad flu," Sgt Civitello said.

Twenty-seven other volunteers in the study had been given varying doses of the vaccine for several months prior to infection.

Developed by scientists at the Walter Reed Army Institute of Research, it consists of a protein that stimulates the body's immune system and triggers its natural defences against the disease.

Then, at the beginning of November, they were bitten by mosquitoes imported from Thailand and infected with Plasmodium vivax malaria.

A small carton containing the insects was placed on their arms for several minutes and repeated until they received five bites each, making infection a certainty.

"What makes this process unique is that we don't know whether a vaccine has worked unless it is exposed to a pathogen - in this case malaria. And malaria can only be transmitted through the bite of a mosquito," says Col Christian Ockenhouse, director of the Malaria Vaccine Research Programme at WRAIR.

A volunteer being bitten by infected mosquitoes to see if the vaccine protects them from malaria

He adds: "What we do here plays a critical, pivotal role in the fight against malaria. Without this model of challenging the human body with malaria, we would be unable to effectively develop and figure out whether a vaccine works or not."

"It costs millions of dollars to test any vaccine and if we can safely eliminate vaccines that don't work and push into further trials those that do show promise, it will save millions of dollars."

Malaria vaccines have remained elusive because of the parasite's ability to rapidly evolve and adapt to its human host.

An international movement

The Gates Foundation has spent $1.4bn fighting the disease and the global campaign involves many organisations from WRAIR to big pharmaceutical companies, such as GlaxoSmithKline.

The US military has been at the forefront of developing vaccines ever since the Civil War because of malaria's ability to disrupt operations if soldiers get sick. The Plasmodium vivax strain is a particular problem for troops serving in Afghanistan.

At the moment, the only other way to prevent infection is to avoid mosquito bites by using bed nets or insecticides.

But a trial for a Plasmodium falciparum malaria vaccine, involving 16,000 children in Africa, could be completed next year.

Volunteers in the world's first Plasmodium vivax malaria vaccine trial are given several thousand dollars in compensation.

They say the money is an incentive, but most take part because they want to further medical science.

"My dad was a doctor, and I always knew that in order to advance the medical field you need human subjects," says Mengee Shan, a volunteer in the control group.

"And being a science major myself, I felt I would have to rethink my career if I couldn't dedicate myself to doing something like this, especially if I am going to ask others to take part in my medical projects."

Renee Kruger, a single mother from Maryland, says the cash will help pay for Christmas but feels she's doing something worthwhile.

"Some people may be scared of doing this, but every drug or over-the-counter medicine needed to be tested on a human, so that's why I'm doing it."

Twelve days after being bitten, she exhibits no signs of infection, but other vaccine testers are showing positive for malaria.

Pending results

Scientists say it'll be another week before they can determine full extent of the trial's success or failure.

The vaccine may have offered limited protection to some of the volunteers or be completely effective in others.

Volunteers in the Plassmodium vivax malaria vaccine trial are paid several thousand dollars each
Volunteers in the Plasmodium vivax malaria vaccine trial are paid several thousand dollars each

In any event, the results will be used to develop better vaccines in the future.

"It typically takes 15 to 20 years to develop a new drug or vaccine that goes to market," says Col Ockenhouse.

"But the world doesn't have 15 or 20 years to wait for another malaria vaccine - so anything we can do to rapidly progress this development process is most important."

Meanwhile, the volunteers are staying at a hotel in Maryland, where they can be monitored around the clock.

Some of the rooms have been converted into a clinic and laboratory so that blood samples can be tested immediately for any signs of malaria.

If the volunteers do succumb they are instantly treated with drugs to ensure there will be no lasting consequences of the trial.

Source: BBC News http://www.bbc.co.uk/news/world-us-canada-11760859

**To Read the full article and watch the VDO clip, please go to the BBC News page.


HIV Vaccine Study First to Show Some Effectiveness in Preventing HIV

HIV DNA

24 September 2009—A Phase III clinical trial involving more than 16,000 adult volunteers in Thailand has demonstrated that an investigational HIV vaccine regimen was safe and modestly effective in preventing HIV infection. According to final results released by the trial sponsor, the U.S. Army Surgeon General, the prime boost combination of ALVAC? HIV and AIDSVAX? B/E  lowered the rate of HIV infection by 31.2% compared with placebo.  

In the final analysis, 74 placebo recipients became infected with HIV compared to 51 in the vaccine regimen arm. The efficacy result is considered statistically significant with a 95% confidence interval greater than zero. The vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study.

This is the first time that an HIV vaccine candidate has reduced the risk of HIV infection in humans. This finding has important implications for the design of future HIV vaccines and how they are tested, however the public health benefits are unclear and require further study. In addition, the data show that the vaccine regimen is safe.

Collaborating partners on this study, referred to as RV144, include the U.S. Army, the Thai Ministry of Public Health, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Mahidol University, The Royal Thai Army, AFRIMS-Thai component, sanofi pasteur, and Global Solutions for Infectious Disease (GSID). The collaborators are already working with external experts to determine the need for additional studies on this vaccine regimen.

The U.S. Army Medical Directorate – Armed Forces Research Institute of Medical Sciences (USAMD-AFRIMS), a special foreign activity of the Walter Reed Army Institute of Research (WRAIR) in Washington, D.C. and of the US Army Medical Research and Materiel Command (USAMRMC), helped to execute the trial in Thailand on behalf of the Sponsor.  With enthusiastic support from the US Ambassador to Thailand, this successful vaccine trial is another example of long–standing, productive collaboration between US and Thai military and civilian scientists to conduct basic and applied research on infectious diseases of global health and military importance.  

The U.S. Army would like to thank the more than 16,000 Thai men and women who consented to participate in this trial and the efforts of the Thai Ministry of Public Health and all collaborators for their hard work in achieving this important milestone.


Phase III HIV Vaccine Trial Background

The Thai Phase III clinical vaccine trial (RV 144) tested a prime boost vaccine strategy that combined two vaccines based on strains (subtypes) of HIV that circulate in Thailand. The first, or “prime” vaccine, known as ALVAC HIV, was developed by sanofi pasteur and the booster vaccine, AIDSVAX B/E, was originally developed by VaxGen and is now licensed to Global Solutions for Infectious Diseases.

The study, which began in 2003, was designed to test the vaccine strategy’s ability to prevent HIV infection, as well as its ability to reduce the amount of HIV in the blood of those who became infected after they enrolled in the study.

More than 16,000 HIV-negative men and women between the ages of 18 to 30 participated in the study; half of these participants received the prime-boost vaccine regimen and half received placebo. Volunteers received vaccinations over the course of six months, and were followed for an additional three years. Before agreeing to participate, all volunteers were informed of the potential risks associated with receiving the experimental vaccine regimen used in this study and consented to participate in the study. Volunteers continued to receive an HIV test every six months for three years following vaccination, in addition to counseling on how to prevent becoming infected with HIV.

For additional information regarding the trial, visit www.hivresearch.org

Media inquiries can be directed to Tawn Chatchavalvong of Hill &Knowlton, Thailand at +66 (2) 6273501 ext. 118 or tchatchavalvong@th.hillandknowlton.com

 

 

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