Study offers insights into failed HIV-1 vaccine trial
July 20, 2009Following the disbandment of the STEP trial to test the efficacy of the Merck HIV-1 vaccine candidate in 2007, the leading explanation for why the vaccine was ineffective - and may have even increased susceptibility to acquiring the virus - centered on the hypothesis that high levels of baseline Ad5-specific neutralizing antibodies may have increased HIV-1 acquisition among the study subjects who received the vaccine by increasing Ad5-specific CD4+ T-cells that were susceptible to HIV-1 infection.
Now, a study by Dan Barouch, MD, PhD, and a scientific team at Beth Israel Deaconess Medical Center (BIDMC), reported in the July 20 Advance Online issue of Nature Medicine, shows this was likely not the case.
"Our findings demonstrate that there is no correlation between Ad5 neutralizing antibodies and T-cell immune responses," explains Barouch, who is Chief of the Division of Vaccine Research at BIDMC and Associate Professor of Medicine at Harvard Medical School. "Moreover, subjects with baseline Ad5-specific neutralizing antibodies did not develop higher levels of Ad5-specific T-cell responses as compared with subjects without baseline Ad5-specific neutralizing antibodies."
The Ad5 virus is a weakened form of adenovirus, which is responsible for the common cold and is extremely widespread in the general population. In the Merck vaccine candidate, Ad5 was used as a vector to transport three HIV-1 genes, a strategy that helps to overcome limitations posed by the HIV-1 virus.
"Because HIV-1 does not appear to respond to conventional vaccine strategies, which work by triggering the body's immune system to manufacture antibodies against an infectious organism, the STEP trial was testing a vaccine that would, instead, stimulate the immune system's killer T-cells to root out and disable the virus," explains Barouch. While this method does not eradicate HIV-1, the thinking is that it helps the immune system launch a more aggressive response in the event a person is exposed to HIV-1.
However, prior exposure to the Ad5 cold virus leaves a large number of individuals with baseline neutralizing antibodies against Ad5. "This raised the possibility that these antibodies were triggering production of Ad5-specific T-cells [CD4+] that were susceptible to HIV-1 infection, thereby leaving study subjects at greater risk of acquiring the virus itself," explains Barouch. "But our findings challenge this hypothesis. It does not appear that the potential enhancement of the HIV-1 infection in the STEP study was the result of these secondary, vector-specific CD4+ T-cell responses."
Going forward, Barouch suggests another alternative.
"Safety considerations, including the possibility that vector-specific cellular immunity may impact HIV-1 susceptibility, have become major concerns for the HIV-1 vaccine field," notes Barouch. "Our findings suggest a path forward for HIV-1 vaccine development by using rare serotype vectors [not typically found in the general population] that are not suppressed by high levels of baseline vector-specific neutralizing antibodies." Barouch and colleagues are currently conducting Phase 1 clinical trials to test two such novel HIV-1 vaccines.
Source: Beth Israel Deaconess Medical Center
-
How HIV vaccine might have increased odds of infection
Nov 03, 2008 |
not rated yet |
0
-
Scientists gain insight into HIV vaccine failure
Jul 20, 2009 |
not rated yet |
0
-
NIAID will not move forward with the PAVE 100 HIV Vaccine Trial
Jul 17, 2008 |
not rated yet |
0
-
T cell-based HIV vaccine candidate demonstrates positive results
Nov 09, 2008 |
not rated yet |
0
-
Clinical trial will test new HIV/AIDS vaccine
Apr 03, 2008 |
not rated yet |
0
-
Engineers build first sub-10-nm carbon nanotube transistor
Feb 01, 2012 |
4.9 / 5 (31) |
30
-
Something old, something new: Evolution and the structural divergence of duplicate genes
Jan 31, 2012 |
4.6 / 5 (7) |
1
-
The hidden nanoworld of ice crystals: Revealing the dynamic behavior of quasi-liquid layers
Jan 30, 2012 |
5 / 5 (3) |
1
-
Stock market network reveals investor clustering
Jan 27, 2012 |
3.9 / 5 (23) |
8
-
Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes
Jan 26, 2012 |
5 / 5 (1) |
0
-
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011
- More from Physics Forums - Independent Research
More news stories
Injured boomers beware: Know when to see doctor
(AP) -- It happened to nurse Jane Byron years after an in-line skating fall, business owner Haralee Weintraub while doing "men's" push-ups, and avid cyclist Gene Wilberg while lifting a heavy box.
1 hour ago |
not rated yet |
0
FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice
Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...
Medicine & Health / Neuroscience
Feb 09, 2012 |
4.9 / 5 (53) |
21
|
Green tea found to reduce disability in the elderly
(Medical Xpress) -- A lot of research has been done over the past several years looking into the health benefits of green tea. As a result, scientists have found that regular consumption of the beverage leads ...
Teen school drop-outs three times as likely to be on benefits in later life
Teen school drop-outs are almost three times as likely to be on benefits in later life as their peers who complete their schooling, indicates research published online in the Journal of Epidemiology and Community Health.
Feb 06, 2012 |
not rated yet |
13
To perform with less effort, practice beyond perfection
Whether you are an athlete, a musician or a stroke patient learning to walk again, practice can make perfect, but more practice may make you more efficient, according to a surprising new University of Colorado Boulder study.
Medicine & Health / Neuroscience
Feb 09, 2012 |
4.4 / 5 (15) |
6
|
Google might launch Drive for cloud storage soon
(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...
Latin America mining boom clashes with conservation
Latin America is experiencing a mining boom as prices rise fuelled by a hike in global demand, but the region is also being hit by a wave of violent protests, strikes and rallies by environmentalists.
Love a click away in Indonesia's Twitter Republic
He was a geeky kid from Yogyakarta, she a glamorous city girl in Jakarta. In a country with one of the world's most vibrant social networking scenes they fell in love on Twitter.
Europeans protest controversial Internet pact
Tens of thousands of people marched in protests in more than a dozen European cities Saturday against a controversial anti-online piracy pact that critics say could curtail Internet freedom.
Walney offshore wind farm is world's biggest (for now)
(PhysOrg.com) -- The Walney wind farm on the Irish Sea--characterized by high tides, waves and windy weather--officially opened this week. The farm is treated in the press as a very big deal as the Walney ...
Navy to begin tests on electromagnetic railgun prototype launcher
The Office of Naval Research (ONR)'s Electromagnetic (EM) Railgun program will take an important step forward in the coming weeks when the first industry railgun prototype launcher is tested at a facility ...
Jul 23, 2009
Rank: not rated yet