AIDSVAX
Encyclopedia
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 proved inconclusive. The vaccine was then tested on a group of at-risk individuals in Thailand
.
In 1991, AIDSVAX originally consisted of the B envelope of recombinant gp120
, a glycoprotein
unique to HIV's surface, from a strain of the virus
, MN, known at the time to infect victims in the United States
and Europe
. The vaccine was designed to provoke the production of antibodies in subjects that would strip the gp120 protein off of the HIV viral particles, effectively disabling the virus so that it could not bind to or invade susceptible cell
s. Then, another group of victims, infected with a second strain of HIV, A244, was discovered in 1995, and a revised, bivalent version of the vaccine was produced that combined elements of both MN and A244. Phase I and Phase II tests of the first version were promising, showing excellent safety in chimpanzees and humans and provoking production of HIV MN and A244 antibodies in 99% of human volunteers.
VaxGen's leadership enthusiastically applied to the U.S. Food and Drug Administration
(FDA) for permission to undertake Phase III studies in the U. S. on large numbers of at-risk volunteers. But since some of the Phase I and Phase II volunteers had become infected with HIV while taking the vaccine, showing that the vaccine was not 100% effective, and it was not proven that the vaccine itself hadn't caused these infections, the FDA and other members of the medical community hesitated and finally declined to approve Phase III testing "until more was learned about HIV immunity
", despite the fact that early versions of successful vaccines have rarely been 100% effective, and even the 1955 Salk polio vaccine was only 70% effective, superseded as it was seven years later by the Sabin vaccine. With human lives at stake, however, the FDA could not risk condoning further trials until it knew what had caused the infections.
Another problem with AIDSVAX was that it provoked an entirely humoral, antibody immune response in its subjects, unlike other AIDS vaccines in development in Europe
and elsewhere that were provoking balanced antibody and cellular defenses.
So VaxGen turned to the international community, seeking a place that would sanction clinical trials of AIDSVAX, and after negotiating with AIDS-plagued officials in Africa
and Asia
, landed upon Thailand
, the nation in Asia with the highest percentage of AIDS-infected individuals--6% and growing by 8500 a day. Initial Phase II trials of AIDSVAX B/B alone in the US and AIDVAX B/E alone in Thailand were unsuccessful, with both vaccines failing to either prevent or weaken HIV infection, so instead VaxGen began Thai trials of AIDSVAX B/E in combination with the Aventis-Pasteur vaccine, ALVAC-HIV, that uses genetic elements of several different HIV strains encapsulated in a harmless canarypox virus vector
. AIDSVAX B/E, moreover, contained elements of the HIV strain peculiar to Thailand's victims, E, as well as one common in the US, B.
A report published in the December 2009 New England Journal of Medicine
on this latest Thailand clinical trial of the vaccine known as "ALVAC-AIDSVAX B/E" showed the combination treatment's efficacy ranging from 26.1 to 31.4%, which though far from optimal makes the combination AIDSVAX-Aventis vaccine one of the first important milestones in the world's struggle to produce a globally effective HIV/AIDS vaccine.
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
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
that was developed originally at 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...
in San Francisco, California
San Francisco, California
San Francisco , officially the City and County of San Francisco, is the financial, cultural, and transportation center of the San Francisco Bay Area, a region of 7.15 million people which includes San Jose and Oakland...
, and later tested by the 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...
company, a Genentech offshoot. The development and trials of the vaccine received significant coverage in the international media, but American trials proved inconclusive. The vaccine was then tested on a group of at-risk individuals 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...
.
In 1991, AIDSVAX originally consisted of the B envelope of recombinant gp120
Gp120
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons...
, a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
unique to HIV's surface, from a strain of the virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
, MN, known at the time to infect victims in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
. The vaccine was designed to provoke the production of antibodies in subjects that would strip the gp120 protein off of the HIV viral particles, effectively disabling the virus so that it could not bind to or invade susceptible cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s. Then, another group of victims, infected with a second strain of HIV, A244, was discovered in 1995, and a revised, bivalent version of the vaccine was produced that combined elements of both MN and A244. Phase I and Phase II tests of the first version were promising, showing excellent safety in chimpanzees and humans and provoking production of HIV MN and A244 antibodies in 99% of human volunteers.
VaxGen's leadership enthusiastically applied to the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) for permission to undertake Phase III studies in the U. S. on large numbers of at-risk volunteers. But since some of the Phase I and Phase II volunteers had become infected with HIV while taking the vaccine, showing that the vaccine was not 100% effective, and it was not proven that the vaccine itself hadn't caused these infections, the FDA and other members of the medical community hesitated and finally declined to approve Phase III testing "until more was learned about HIV immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
", despite the fact that early versions of successful vaccines have rarely been 100% effective, and even the 1955 Salk polio vaccine was only 70% effective, superseded as it was seven years later by the Sabin vaccine. With human lives at stake, however, the FDA could not risk condoning further trials until it knew what had caused the infections.
Another problem with AIDSVAX was that it provoked an entirely humoral, antibody immune response in its subjects, unlike other AIDS vaccines in development in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
and elsewhere that were provoking balanced antibody and cellular defenses.
So VaxGen turned to the international community, seeking a place that would sanction clinical trials of AIDSVAX, and after negotiating with AIDS-plagued officials in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
and Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, landed upon 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...
, the nation in Asia with the highest percentage of AIDS-infected individuals--6% and growing by 8500 a day. Initial Phase II trials of AIDSVAX B/B alone in the US and AIDVAX B/E alone in Thailand were unsuccessful, with both vaccines failing to either prevent or weaken HIV infection, so instead VaxGen began Thai trials of AIDSVAX B/E in combination with the Aventis-Pasteur vaccine, ALVAC-HIV, that uses genetic elements of several different HIV strains encapsulated in a harmless canarypox virus 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...
. AIDSVAX B/E, moreover, contained elements of the HIV strain peculiar to Thailand's victims, E, as well as one common in the US, B.
A report published in the December 2009 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:...
on this latest Thailand clinical trial of the vaccine known as "ALVAC-AIDSVAX B/E" showed the combination treatment's efficacy ranging from 26.1 to 31.4%, which though far from optimal makes the combination AIDSVAX-Aventis vaccine one of the first important milestones in the world's struggle to produce a globally effective HIV/AIDS vaccine.