RV 144
Encyclopedia
RV 144
, or the Thai trial
, is the name of an HIV
vaccine clinical trial
combining two vaccines that failed on their own, vaccinating in Thailand
over the course of 24 weeks in October 2003 then testing for HIV until July 2006http://www.nature.com/news/2009/090924/full/news.2009.947.html, publicly releasing efficacy findings in September 2009. The initial report shows that the rate of HIV infection among volunteers who received the experimental vaccine was 31% lower than the rate of HIV infection in volunteers who received the placebo
.
The trial collaborators have stated that results of this trial give the first supporting evidence of any vaccine being effective in lowering the risk of contracting HIV. On October 20, the organizers released full results of the study through publishing in the New England Journal of Medicine
(PMID 19843557) and presented them at the AIDS Vaccine Conference in Paris.
Provinces in Thailand. These volunteers were randomized into double-blind study groups, with those in the experimental group receiving a phase III prime-boost HIV vaccine
. Eligibility criteria for participation in the study required that all volunteers be HIV negative prior to enrollment in the study and be willing to participate in educational counseling intended to teach ways to reduce risk behavior associated with contracting HIV. After being vaccinated, volunteers were asked to receive HIV testing every six months for three years, as well as receive additional risk-behavior counseling at every testing visit.
A separate but related result is that the vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study.
As with all major studies, the data for this one were analyzed in different ways to get different interpretations.
In May 2011, a new analysis initiated at Duke University
showed that there is a 29% chance that the vaccine is not effective (not 4% as assumed before).
Their work isn't complete, but those in the study who produced the antibody immunoglobulin G (IgG) were 43% less likely to become infected. IgG recognises the V2 loop in HIV's outer envelope. Those who produced IgA were 54% more likely to become infected, but no more susceptible than trial subjects receiving the placebo.
The immune responses of uninfected patients could point the way to more fruitful research. Nelson Michael, director of the U.S. Military HIV Research Program, says, "This lends biological credence to the initial clinical study results ... It suggests that what happened in RV144 was related to vaccination."
"You might say this is the most successful experiment we've had so far," says Adriano Boasso, an immunologist at Imperial College London.
ALVAC‐HIV (vCP1521) consists of a viral vector
containing genetically engineered versions of three HIV genes (env, gag and pro). The ALVAC vector is an inert form of canarypox, which is a bird virus which cannot cause disease or replicate in humans. AIDSVAX
B/E is composed of genetically engineered gp120, a protein on the surface of HIV.
with support from the United States Army Medical Research and Materiel Command
and the National Institute of Allergy and Infectious Diseases
, which is part of the National Institutes of Health
.
ALVAC‐HIV (vCP1521) was manufactured by Sanofi Pasteur
. AIDSVAX B/E was manufactured by Genentech
under a license and supply agreement with VaxGen
, which itself is a spin-off company of Genentech founded for the purpose of developing AIDSVAX. Global Solutions for Infectious Diseases, a nonprofit organization co‐founded by former VaxGen executives, has ownership of certain intellectual and manufacturing rights of AIDSVAX.
RV 144
RV 144, or the Thai trial, is the name of an HIV vaccine clinical trial combining two vaccines that failed on their own, vaccinating in Thailand over the course of 24 weeks in October 2003 then testing for HIV until July 2006, publicly releasing efficacy findings in September 2009...
, or the Thai trial
RV 144
RV 144, or the Thai trial, is the name of an HIV vaccine clinical trial combining two vaccines that failed on their own, vaccinating in Thailand over the course of 24 weeks in October 2003 then testing for HIV until July 2006, publicly releasing efficacy findings in September 2009...
, is the name of an HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
vaccine clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
combining two vaccines that failed on their own, vaccinating in Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
over the course of 24 weeks in October 2003 then testing for HIV until July 2006http://www.nature.com/news/2009/090924/full/news.2009.947.html, publicly releasing efficacy findings in September 2009. The initial report shows that the rate of HIV infection among volunteers who received the experimental vaccine was 31% lower than the rate of HIV infection in volunteers who received the placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
.
The trial collaborators have stated that results of this trial give the first supporting evidence of any vaccine being effective in lowering the risk of contracting HIV. On October 20, the organizers released full results of the study through publishing in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
(PMID 19843557) and presented them at the AIDS Vaccine Conference in Paris.
Protocol
16,402 Thai volunteers aged 18–30 were recruited to participate in Chon Buri and RayongRayong Province
Rayong province is a province of Thailand. Neighboring provinces are Chon Buri and Chanthaburi. To the south is the Gulf of Thailand.-History:...
Provinces in Thailand. These volunteers were randomized into double-blind study groups, with those in the experimental group receiving a phase III prime-boost HIV vaccine
HIV vaccine
An HIV vaccine that protects vaccinated individuals from HIV infection is the goal of many HIV research programmes. Currently, there is no effective vaccine against HIV, the virus that causes AIDS...
. Eligibility criteria for participation in the study required that all volunteers be HIV negative prior to enrollment in the study and be willing to participate in educational counseling intended to teach ways to reduce risk behavior associated with contracting HIV. After being vaccinated, volunteers were asked to receive HIV testing every six months for three years, as well as receive additional risk-behavior counseling at every testing visit.
Results
During the study, 125 of the 16,402 participants contracted HIV through behavior unrelated to their study participation. Of those 125, 74 infected persons had received placebo and 51 had received the vaccine. It is statistically significant that the group which received the vaccine has an infection rate 31.2% lower than the group who received placebo.A separate but related result is that the vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study.
As with all major studies, the data for this one were analyzed in different ways to get different interpretations.
In May 2011, a new analysis initiated at Duke University
Duke University
Duke University is a private research university located in Durham, North Carolina, United States. Founded by Methodists and Quakers in the present day town of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco industrialist James B...
showed that there is a 29% chance that the vaccine is not effective (not 4% as assumed before).
Cautious optimismhttp://www.nature.com/news/2011/110916/full/news.2011.541.html?WT.mc_id=TWT_NatureNews
In a study in September 2011, researchers involved with the trial at Mahidol University in Bangkok and the U.S. Military HIV Research Program in Washington DC tested the blood of trial subjects for different immune indicators between those who received the vaccine and contracted HIV (41 subjects) and those who did not become infected (205 subjects).Their work isn't complete, but those in the study who produced the antibody immunoglobulin G (IgG) were 43% less likely to become infected. IgG recognises the V2 loop in HIV's outer envelope. Those who produced IgA were 54% more likely to become infected, but no more susceptible than trial subjects receiving the placebo.
The immune responses of uninfected patients could point the way to more fruitful research. Nelson Michael, director of the U.S. Military HIV Research Program, says, "This lends biological credence to the initial clinical study results ... It suggests that what happened in RV144 was related to vaccination."
"You might say this is the most successful experiment we've had so far," says Adriano Boasso, an immunologist at Imperial College London.
Vaccine composition
Over six months, volunteers received a prime-boost vaccination including six injections of a vaccine called ALVAC HIV (vCP1521) with the last two of the six injections being a combination of that vaccine and another one called AIDSVAX B/E (gp120).ALVAC‐HIV (vCP1521) consists of a viral vector
Viral vector
Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture . Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect...
containing genetically engineered versions of three HIV genes (env, gag and pro). The ALVAC vector is an inert form of canarypox, which is a bird virus which cannot cause disease or replicate in humans. AIDSVAX
AIDSVAX
AIDSVAX is an experimental HIV vaccine that was developed originally at Genentech in San Francisco, California, and later tested by the VaxGen company, a Genentech offshoot. The development and trials of the vaccine received significant coverage in the international media, but American trials...
B/E is composed of genetically engineered gp120, a protein on the surface of HIV.
Study Sponsors
RV 144 is sponsored by the Surgeon General of the United States Army and conducted by the Thailand Ministry of Public HealthMinistry of Public Health (Thailand)
The Ministry of Public Health , is a Thai government body responsible for the oversight of Public Health in Thailand.-External links:* - Official Website in Thai* - Official Website in English...
with support from the United States Army Medical Research and Materiel Command
United States Army Medical Research and Materiel Command
The United States Army Medical Research and Materiel Command is the United States Army's medical materiel developer, with responsibility for medical research, development, and acquisition and medical logistics management. The USAMRMC's expertise in these critical areas helps establish and maintain...
and the National Institute of Allergy and Infectious Diseases
National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...
, which is part of the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
.
ALVAC‐HIV (vCP1521) was manufactured by Sanofi Pasteur
Sanofi pasteur
Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...
. AIDSVAX B/E was manufactured by Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...
under a license and supply agreement with VaxGen
VaxGen
VaxGen is a biopharmaceutical company based in the San Francisco Bay Area.As of July 28, 2010, VaxGen Inc. was acquired by diaDexus, Inc., in a reverse merger transaction. VaxGen, Inc. does not have significant operations. The company seeks to enter into a strategic transaction or series of...
, which itself is a spin-off company of Genentech founded for the purpose of developing AIDSVAX. Global Solutions for Infectious Diseases, a nonprofit organization co‐founded by former VaxGen executives, has ownership of certain intellectual and manufacturing rights of AIDSVAX.