In mice, a step towards a vaccine for HIV
Tests on lab mice have opened up a new path towards a vaccine against HIV, one of the most frustrating quests in the 30-year history of AIDS, scientists reported on Wednesday.
Genetically modified mice fought back the human immunodeficiency virus (HIV) after they had been injected with genes to make antibodies, the first line of defence in the immune system, the report said in the journal Nature.
First identified in 1981, AIDS has claimed at least 25 million lives, although the annual toll is falling sharply from the peak of the pandemic in response to drug treatment.
But AIDS campaigners say the pandemic will only be crushed once a vaccine emerges. So far, in clinical trials, only one candidate formula has had even a modest effect, providing a shield of only 31 percent against the risk of HIV infection.
This has prompted researchers to return to the drawing board, to look for "broadly neutralising antibodies" -- Y-shaped proteins that are the immune system's foot soldiers -- among the tiny number of people with an innate ability to resist HIV.
So far, this trawl has turned up around 20 so-called "bNAbs," but there are big unknowns as to how they work and, if so, whether they can be made into a deliverable vaccine.
Delving into this, a team led by David Baltimore at the California Institute of Technology (Caltech) says it has developed a way to deliver bNAb-making genes to lab mice.
The rodents were engineered to carry human cells that allow HIV to penetrate and reproduce.
The approach, called Vectored ImmunoProphylaxis, or VIP, entails using a harmless virus as a "Trojan horse" in which they tucked the genes able to turn out specific bNAbs.
They then injected the virus into the leg muscles of the mice, where it holed up in cells, enabling the bNAb genes to produce antibodies in response to HIV.
The mice were first challenged with just one nanogram of AIDS virus -- enough to infect most non-treated mice that received it -- but the dose was eventually cranked up to 125 nanograms without problems. There were no signs of any side effects.
"VIP has a similar effect to a vaccine but without ever calling on the immune system to do any of the work," said Alejandro Balazs, lead author of the study, in a press release issued by Caltech.
"Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it. We've taken that whole part out of the equation."
The team stressed that the jump from mice to humans is large.
"We're not promising that we've actually solved the human problem," said Baltimore. "But the evidence for prevention in these mice is very clear."
He added the team was drawing up plans to cautiously test the method in small-scale human clinical trials.
Baltimore co-won the 1975 Nobel Prize for Medicine at the age of 37 for his work on reverse transcriptase, a key enzyme in the reproduction of retroviruses -- the family that includes HIV.
In an email exchange with AFP, he said VIP was "like gene therapy, but distinct."
Gene therapy entails slotting a gene into the patient's DNA that corrects a flawed, disease-causing counterpart.
Hopes for this field of research were clouded by several reverses, notably the death of a young volunteer, Jesse Gelsinger, in 1999.
The tragedy raised doubts about where genes should be inserted in the genome and about the safety of the virus that delivered them.
Baltimore explained that VIP used a small, harmless vector, an adeno-associated virus (AAV), which took up residence in the muscle cells but did not slot genes into the mouse's DNA code.
"It's not an 'insertion' but a free plasmid-like element that will exist in muscle cells," he said.
Publication of the study coincided with the eve of World AIDS Day.
The number of people living with HIV currently stands at about 34 million, according to the latest UN figures.
Wednesday, November 30, 2011
Tuesday, June 21, 2011
First man ‘functionally cured’ of HIV
Fri Jun 3, 5:40 pm ET
First man ‘functionally cured’ of HIV
By Liz Goodwin liz Goodwin – Fri Jun 3, 5:40 pm ET
Since HIV was discovered 30 years ago this week, 30 million people have died
from the disease, and it continues to spread at the rate of 7,000 people per day
globally, the UN says.
There's not much good news when it comes to this devastating virus. But that is
perhaps why the story of the man scientists call the "Berlin patient" is so
remarkable and has generated so much excitement among the HIV advocacy
community.
Timothy Ray Brown suffered from both leukemia and HIV when he received a bone
marrow stem cell transplant in Berlin, Germany in 2007. The transplant came from
a man who was immune to HIV, which scientists say about 1 percent of Caucasians
are. (According to San Francisco's CBS affiliate, the trait may be passed down
from ancestors who became immune to the plague centuries ago. This Wired story
says it was more likely passed down from people who became immune to a
smallpox-like disease.)
What happened next has stunned the dozens of scientists who are closely
monitoring Brown: His HIV went away.
"He has no replicating virus and he isn't taking any medication. And he will now
probably never have any problems with HIV," his doctor Gero Huetter told
Reuters. Brown now lives in the Bay Area, and suffers from some mild
neurological difficulties after the operation. "It makes me very happy," he says
of the incredible cure.
The development of anti-retroviral drugs in the 1990s was the first sign of hope
in the epidemic, transforming the disease from a sudden killer to a more
manageable illness that could be lived with for decades. But still, the
miraculous cocktail of drugs is expensive, costing $13 billion a year in
developing countries alone, according to Reuters. That figure is expected to
triple in 20 years--raising the worry that more sick people will not be able to
afford treatment.
Although Brown's story is remarkable, scientists were quick to point out that
bone marrow transplants can be fatal, and there's no way Brown's treatment could
be applied to the 33.3 million people around the world living with HIV. The
discovery does encourage "cure research," according to Dr. Jay Levy, who
co-discovered HIV thirty years ago, something that many people did not even
think was possible years ago.
You can watch Brown talk about his cure in this CBS video report.
(Brown: Eric Risberg/AP)
This article has been updated to include more context about why some people are
immune to HIV.
First man ‘functionally cured’ of HIV
By Liz Goodwin liz Goodwin – Fri Jun 3, 5:40 pm ET
Since HIV was discovered 30 years ago this week, 30 million people have died
from the disease, and it continues to spread at the rate of 7,000 people per day
globally, the UN says.
There's not much good news when it comes to this devastating virus. But that is
perhaps why the story of the man scientists call the "Berlin patient" is so
remarkable and has generated so much excitement among the HIV advocacy
community.
Timothy Ray Brown suffered from both leukemia and HIV when he received a bone
marrow stem cell transplant in Berlin, Germany in 2007. The transplant came from
a man who was immune to HIV, which scientists say about 1 percent of Caucasians
are. (According to San Francisco's CBS affiliate, the trait may be passed down
from ancestors who became immune to the plague centuries ago. This Wired story
says it was more likely passed down from people who became immune to a
smallpox-like disease.)
What happened next has stunned the dozens of scientists who are closely
monitoring Brown: His HIV went away.
"He has no replicating virus and he isn't taking any medication. And he will now
probably never have any problems with HIV," his doctor Gero Huetter told
Reuters. Brown now lives in the Bay Area, and suffers from some mild
neurological difficulties after the operation. "It makes me very happy," he says
of the incredible cure.
The development of anti-retroviral drugs in the 1990s was the first sign of hope
in the epidemic, transforming the disease from a sudden killer to a more
manageable illness that could be lived with for decades. But still, the
miraculous cocktail of drugs is expensive, costing $13 billion a year in
developing countries alone, according to Reuters. That figure is expected to
triple in 20 years--raising the worry that more sick people will not be able to
afford treatment.
Although Brown's story is remarkable, scientists were quick to point out that
bone marrow transplants can be fatal, and there's no way Brown's treatment could
be applied to the 33.3 million people around the world living with HIV. The
discovery does encourage "cure research," according to Dr. Jay Levy, who
co-discovered HIV thirty years ago, something that many people did not even
think was possible years ago.
You can watch Brown talk about his cure in this CBS video report.
(Brown: Eric Risberg/AP)
This article has been updated to include more context about why some people are
immune to HIV.
Lessons from HIV/AIDS Advocacy
This month marks 30 years since the first case reports were published about
HIV, the virus that causes AIDS. A new report analyzes the factors that
helped patient advocates drive research into and drug development for that
disease, and tries to figure out whether there are lessons to be learned for
other disease advocates.
The paper, called "Back to Basics: HIV/AIDS Advocacy as a Model for
Catalyzing Change" and co-authored by consulting-firm HCM Strategists and
the nonprofit group FasterCures, is based on in-person and telephone
interviews with activists, scientists, government officials and policy
makers involved with the HIV/AIDS advocacy movement. It credits patient
advocates with helping to implement regulatory changes that speed up access
to investigatory drugs and with ushering in an era where patients are taken
seriously and their views represented on governmental and scientific
committees.
While advocates now have a level of access and face time with policy makers
and officials that took years for HIV/AIDS activists to win, the report
argues that this doesn't mean advocates "have their attention and, in some
instances, it only means that the decision makers can 'check the box' about
consulting with the community without having really listened.'' In the past
decades, patient-driven foundations have raised huge amounts of money to
help fund research and have hired scientists to staff their organizations.
But it's still crucial to have an actual patient sitting at the table along
with the scientists, drug company executives, and policy makers, the report
says. Patients shouldn't simply "defer to the organizations and scientists
representing their interests."
There are some specific steps taken by yesterday's HIV/AIDS advocates that
could help today's advocates be more effective. Among them: focusing on
specific problems that hold back research or drug development and proposing
solutions; creating a sense of community among advocates so that different
groups are driving towards a common goal; training patient advocates to
understand the scientific and policy issues in their disease and figuring
out the key issue limiting research progress and then developing an approach
to fix it.
HIV, the virus that causes AIDS. A new report analyzes the factors that
helped patient advocates drive research into and drug development for that
disease, and tries to figure out whether there are lessons to be learned for
other disease advocates.
The paper, called "Back to Basics: HIV/AIDS Advocacy as a Model for
Catalyzing Change" and co-authored by consulting-firm HCM Strategists and
the nonprofit group FasterCures, is based on in-person and telephone
interviews with activists, scientists, government officials and policy
makers involved with the HIV/AIDS advocacy movement. It credits patient
advocates with helping to implement regulatory changes that speed up access
to investigatory drugs and with ushering in an era where patients are taken
seriously and their views represented on governmental and scientific
committees.
While advocates now have a level of access and face time with policy makers
and officials that took years for HIV/AIDS activists to win, the report
argues that this doesn't mean advocates "have their attention and, in some
instances, it only means that the decision makers can 'check the box' about
consulting with the community without having really listened.'' In the past
decades, patient-driven foundations have raised huge amounts of money to
help fund research and have hired scientists to staff their organizations.
But it's still crucial to have an actual patient sitting at the table along
with the scientists, drug company executives, and policy makers, the report
says. Patients shouldn't simply "defer to the organizations and scientists
representing their interests."
There are some specific steps taken by yesterday's HIV/AIDS advocates that
could help today's advocates be more effective. Among them: focusing on
specific problems that hold back research or drug development and proposing
solutions; creating a sense of community among advocates so that different
groups are driving towards a common goal; training patient advocates to
understand the scientific and policy issues in their disease and figuring
out the key issue limiting research progress and then developing an approach
to fix it.
SOUTH AFRICA: Top five recent successes in HIV
Making progress
DURBAN, 8 June 2011 (PlusNews) - South Africa's
HIV/AIDS programme has come a long way from the dark days of denialism
and deadly treatment delays. Francois Venter, chairman of the
country's bi-annual HIV conference, SA AIDS 2011, gave IRIN/PlusNews
five reasons to be happy about the countrys progress:
1. Testing - About 12 million people in South Africa have been tested
for HIV in the past year, representing just under a quarter of the
total population.
2. Antiretroviral prices - ARV drug costs have been halved in the past
six months, because of the countrys recently negotiated ARV tender.
HIV is now one of the cheapest chronic conditions to treat in the
South African public health system.
3. Treatment - Nearly 1.4 million South Africans are on ARVs - still
less than half of those in need. But of the 1.4 million on treatment,
400,000 were initiated in the past year. The programme hopes to have
2.3 million on treatment by the end of 2012, according to Venter, who
is also deputy executive director of the Wits Institute for Sexual &
Reproductive Health, HIV and Related Diseases. Over 5 million South
Africans are living with HIV.
At present, 1,668 public health facilities provide ARVs in South Africa.
4. Tuberculosis - South Africa has finally begun to tackle TB.
Although about 70 percent of TB patients are co-infected with HIV, TB
has been the orphan of the health world for decades, Venter told
IRIN/PlusNews.
[TB] has been mismanaged and hasnt been given the resources it
deserves. For the first time, its being regarded as the emergency it
actually is, he said. For the first time, were seeing the drugs and
the diagnostics; we need to now start making sure that the health
system is one that allows us to start to tackle it.
5. The re-engineering of the primary healthcare system - Venter called
this initiative one of the most profound changes planned in the past
20 years. Expected to be community-driven, the restructuring of local
health districts is set to increase access to HIV care and treatment.
DURBAN, 8 June 2011 (PlusNews) - South Africa's
HIV/AIDS programme has come a long way from the dark days of denialism
and deadly treatment delays. Francois Venter, chairman of the
country's bi-annual HIV conference, SA AIDS 2011, gave IRIN/PlusNews
five reasons to be happy about the countrys progress:
1. Testing - About 12 million people in South Africa have been tested
for HIV in the past year, representing just under a quarter of the
total population.
2. Antiretroviral prices - ARV drug costs have been halved in the past
six months, because of the countrys recently negotiated ARV tender.
HIV is now one of the cheapest chronic conditions to treat in the
South African public health system.
3. Treatment - Nearly 1.4 million South Africans are on ARVs - still
less than half of those in need. But of the 1.4 million on treatment,
400,000 were initiated in the past year. The programme hopes to have
2.3 million on treatment by the end of 2012, according to Venter, who
is also deputy executive director of the Wits Institute for Sexual &
Reproductive Health, HIV and Related Diseases. Over 5 million South
Africans are living with HIV.
At present, 1,668 public health facilities provide ARVs in South Africa.
4. Tuberculosis - South Africa has finally begun to tackle TB.
Although about 70 percent of TB patients are co-infected with HIV, TB
has been the orphan of the health world for decades, Venter told
IRIN/PlusNews.
[TB] has been mismanaged and hasnt been given the resources it
deserves. For the first time, its being regarded as the emergency it
actually is, he said. For the first time, were seeing the drugs and
the diagnostics; we need to now start making sure that the health
system is one that allows us to start to tackle it.
5. The re-engineering of the primary healthcare system - Venter called
this initiative one of the most profound changes planned in the past
20 years. Expected to be community-driven, the restructuring of local
health districts is set to increase access to HIV care and treatment.
Monday, August 30, 2010
Posible HIV Vaccine
HIV vaccine
An HIV vaccine is the theoretical vaccine which would be given to persons without HIV in order to vaccinate them against getting HIV, the virus which causes AIDS. No effective vaccine against HIV exists. As there is no known cure for AIDS, the search for a vaccine has become part of medical approaches against the disease.
It has been known for many years that HIV is an extremely difficult virus to render harmless, and no cure presently exists. Research into a vaccine is one of several strategies to reduce the worldwide harm from AIDS, with other approaches based upon antiviral treatments such as highly active antiretroviral therapy (HAART), and social approaches such as safe sex.
There is evidence that a vaccine may be possible. Work with monoclonal antibodies (MAb) has proven that the human body can defend itself against HIV, and certain individuals remain asymptomatic for decades after HIV infection. More recently in 2009, a number of potential candidates for antibodies and early stage results from clinical trials have been announced by various teams. However these are early results, and have either not been developed to the point of human testing, or not fully peer reviewed and replicated by other teams, at this time.
Contents
[hide]
* 1 Overview
* 2 Difficulties in developing an HIV vaccine
o 2.1 HIV structure
o 2.2 Animal model
* 3 Clinical trials to date
o 3.1 Phase I
o 3.2 Phase II
o 3.3 Phase III
o 3.4 Planned clinical trials
* 4 Economics of vaccine development
* 5 Future work
* 6 See also
* 7 References
* 8 External links
Overview
The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 25 million people since 1981.[1] Indeed, in 2002, AIDS became the primary cause of mortality due to an infectious agent in Africa.[2]
Alternative medical treatments to a vaccine do exist. Highly active antiretroviral therapy (HAART) has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. HAART allows the stabilization of the patient’s symptoms and viremia, but they do not cure the patient of HIV, nor of the symptoms of AIDS. And, importantly, HAART does nothing to prevent the spread of HIV through people with undiagnosed HIV infections. Safer sex measures have also proven insufficient to halt the spread of AIDS in the worst affected countries, despite some success in reducing infection rates.
Therefore, an HIV vaccine is generally considered as the most likely, and perhaps the only way by which the AIDS pandemic can be halted. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.
[edit] Difficulties in developing an HIV vaccine
In 1984, after the confirmation of the etiological agent of AIDS by scientists at the U.S. National Institutes of Health and the Pasteur Institute, the United States Health and Human Services Secretary Margaret Heckler declared that a vaccine would be available within two years.[citation needed]
However, the classical vaccination approaches that have been successful in the control of various viral diseases by priming the adaptive immunity to recognize the viral envelope proteins have failed in the case of HIV-1. Some have stated that an HIV vaccine may not be possible without significant theoretical advances.[3]
There are a number of factors that cause development of an HIV vaccine to differ from the development of other classic vaccines:[4]
* Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection; there are almost no recovered AIDS patients.
* Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS.
* Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues.
* Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.
* Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract.
HIV structure
The epitopes of the viral envelope are more variable than those of many other viruses. Furthermore, the functionally important epitopes of the gp120 protein are masked by glycosylation, trimerisation and receptor-induced conformational changes making it difficult to block with neutralising antibodies.
The ineffectiveness of previously developed vaccines primarily stems from two related factors.
* First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system, the population of virus in an infected individual typically evolves so that it can evade the two major arms of the adaptive immune system; humoral (antibody-mediated) and cellular (mediated by T cells) immunity.
* Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.
The difficulties in stimulating a reliable antibody response has led to the attempts to develop a vaccine that stimulates a response by cytotoxic T-lymphocytes.[5][6]
Another response to the challenge has been to create a single peptide that contains the least variable components of all the known HIV strains.[7]
[edit] Animal model
The typical animal model for vaccine research is the monkey, often the macaque. Monkeys can be infected with SIV or the chimeric SHIV for research purposes. However, the well-proven route of trying to induce neutralizing antibodies by vaccination has stalled because of the great difficulty in stimulating antibodies that neutralise heterologous primary HIV isolates.[8] Some vaccines based on the virus envelope have protected chimpanzees or macaques from homologous virus challenge,[9] but in clinical trials, individuals who were immunised with similar constructs became infected after later exposure to HIV-1.[10]
There are some differences between SIV and HIV that may introduce challenges in the use of an animal model.[11]
As published on 27 November 2009 in Journal of Biology, there is new animal model strongly resembling that of HIV in humans. Generalized immune activation as a direct result of activated CD4+ T cell killing - performed in mice allows new ways of testing HIV behaviour.[12][13]
[edit] Clinical trials to date
Ambox outdated serious.svg
This article may need to be updated. Please update this article to reflect recent events or newly available information, and remove this template when finished. Please see the talk page for more information. (September 2009)
Several vaccine candidates are in varying phases of clinical trials.
[edit] Phase I
Most initial approaches have focused on the HIV envelope protein. At least thirteen different gp120 and gp160 envelope candidates have been evaluated, in the US predominantly through the AIDS Vaccine Evaluation Group. Most research focused on gp120 rather than gp41/gp160, as the latter are generally more difficult to produce and did not initially offer any clear advantage over gp120 forms. Overall, they have been safe and immunogenic in diverse populations, have induced neutralizing antibody in nearly 100% recipients, but rarely induced CD8+ cytotoxic T lymphocytes (CTL). Mammalian derived envelope preparations have been better inducers of neutralizing antibody than candidates produced in yeast and bacteria. Although the vaccination process involved many repeated "booster" injections, it was very difficult to induce and maintain the high anti-gp120 antibody titers necessary to have any hope of neutralizing an HIV exposure.
The availability of several recombinant canarypox vectors has provided interesting results that may prove to be generalizable to other viral vectors. Increasing the complexity of the canarypox vectors by inclusion of more genes/epitopes has increased the percent of volunteers that have detectable CTL to a greater extent than did increasing the dose of the viral vector. Importantly, CTLs from volunteers were able to kill peripheral blood mononuclear cells infected with primary isolates of HIV, suggesting that induced CTLs could have biological significance. In addition, cells from at least some volunteers were able to kill cells infected with HIV from other clades, though the pattern of recognition was not uniform among volunteers. Canarypox is the first candidate HIV vaccine that has induced cross-clade functional CTL responses. The first phase I trial of the candidate vaccine in Africa was launched early in 1999 with Ugandan volunteers. The study determined the extent to which Ugandan volunteers have CTL that are active against the subtypes of HIV prevalent in Uganda, A and D.
Other strategies that have progressed to phase I trials in uninfected persons include peptides, lipopeptides, DNA, an attenuated Salmonella vector, lipopeptides, p24, etc. Specifically, candidate vaccines that induce one or more of the following are being sought:
* neutralizing antibodies active against a broad range of HIV primary isolates;
* cytotoxic T cell responses in a vast majority of recipients;
* strong mucosal immune responses.
Phase II
On December 13, 2004, the HIV Vaccine Trials Network (HVTN) began recruiting for the STEP study, a 3,000-participant phase II clinical trial of a novel HIV vaccine, at sites in North America, South America, the Caribbean and Australia.[14] The trial was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is a division of the National Institutes of Health (NIH), and the pharmaceutical company Merck & Co. Merck developed the experimental vaccine called V520 to stimulate HIV-specific cellular immunity, which prompts the body to produce T cells that kill HIV-infected cells. In previous smaller trials, this vaccine was found to be safe, because of the lack of adverse effects on the patients. The vaccine showed induced cellular immune responses against HIV in more than half of volunteers.[1]
V520 contains a weakened adenovirus that serves as a carrier for three subtype B HIV genes (gag / pol / nef). Subtype B is the most prevalent HIV subtype in the regions of the study sites. 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 a weakened adenovirus, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. It was announced in September 2007 that the trial for V520 would be discontinued after it determined that the vaccination was ineffective. The foremost issue facing the rAd5 adenovirus that was used is the high prevalence of the adenovirus-specific antibodies as a result of prior exposure to the virus. Adenovirus vectors and many other viral vectors currently used in HIV vaccines, will induce a rapid memory immune response against the vector. This results in an impediment to the development of a T cell response against the inserted antigen (HIV antigens)[15] Additionally, it appears that V520 may have made some recipients more receptive to infection by HIV-1.[16][17]
The HVTN expected to finish the study in 2009, but ceased further treatment administration and declared the vaccine ineffective at preventing HIV-infection in September 2007.[18] The results of the trial have caused some to call for a reexamination of vaccine development strategies.[19]
[edit] Phase III
In February 2003, VaxGen announced that their AIDSVAX vaccine was a failure in North America as there was not a statistically significant reduction of HIV infection within the study population. This same vaccine was retested in Thailand within a vaccine regimen called RV 144 beginning in 2003, with positive results. In both cases the vaccines targeted gp120 and were specific for the geographical regions. The Thai trial was the largest AIDS vaccine trial to date when it started.[20]
In October 2009, the results of the RV 144 trial were published. Initial results, released in September 2009 prior to publication of complete results, were encouraging for scientists in search of a vaccine. The study involved 16,395 participants who did not have HIV infection, 8197 of whom were given treatment consisting of two experimental vaccines targeting HIV types B and E that are prevalent in Thailand, while 8198 were given a placebo. The participants were tested for HIV every six months for three years. After three years, the vaccine group saw HIV infection rates reduced by more than 30% compared with those in the placebo group. However, after taking into account the seven people who had HIV infections at the time of their vaccination (two in the placebo group, five in the vaccine group) the percentage dropped to 26%. [20][21]
[edit] Planned clinical trials
Novel approaches, including modified vaccinia Ankara (MVA), adeno-associated virus, Venezuelan equine encephalitis (VEE) replicons, and codon-optimized DNA have proven to be strong inducers of CTL in macaque models, and have provided at least partial protection in some models. Most of these approaches are in, or will soon enter, clinical studies.
[edit] Economics of vaccine development
A June 2005 study estimates that $682 million is spent on AIDS vaccine research annually.[22]
Economic issues with developing an AIDS vaccine include the need for advance purchase commitment (or advance market commitments) because after an AIDS vaccine has been developed, governments and NGOs may be able to bid the price down to marginal cost.[23]
[edit] Future work
According to Gary J. Nabel of the Vaccine Research Center in Bethesda, Maryland, several hurdles must be overcome before scientific research will culminate in a definitive AIDS vaccine.[24] First, greater translation between animal models and human trials must be established. Second, new, more effective, and more easily produced vectors must be identified. Finally, and most importantly, there must arise a robust understanding of the immune response to potential vaccine candidates. Emerging technologies that enable the identification of T-cell-receptor specificities and cytokine profiles will prove invaluable in hastening this process.
A study that has had success in animal subjects is about to begin human trials in London, Ontario.[25]
[edit] See also
* HIV Vaccine Trials Network
* Subunit HIV vaccine
* World AIDS Vaccine Day
References
1. ^ a b Joint United Nations Programme on HIV/AIDS (UNAIDS) (December 2005). "AIDS epidemic update" (PDF). World Health Organization. http://www.unaids.org/html/pub/publications/irc-pub06/epi_update2005_en_pdf.pdf. Retrieved 2006-01-20.
2. ^ UNAIDS (2004) Report on the global AIDS epidemic, July 2004
3. ^ Watkins DI (Mar 2008). "Basic HIV Vaccine Development". Top HIV Med 16 (1): 7–8. ISSN 1542-8826. PMID 18441377. http://www.iasusa.org/pub/topics/2008/issue1/7.pdf.
4. ^ A. S. Fauci, 1996, An HIV vaccine: breaking the paradigms, Proc. Am. Assoc. Phys. 108:6.
5. ^ Kim D, Elizaga M, Duerr A (March 2007). "HIV vaccine efficacy trials: towards the future of HIV prevention". Infect. Dis. Clin. North Am. 21 (1): 201–17, x. doi:10.1016/j.idc.2007.01.006. ISSN 0891-5520. PMID 17502236. http://linkinghub.elsevier.com/retrieve/pii/S0891-5520(07)00008-6.
6. ^ Watkins DI (March 2008). "The hope for an HIV vaccine based on induction of CD8+ T lymphocytes--a review". Mem. Inst. Oswaldo Cruz 103 (2): 119–29. doi:10.1590/S0074-02762008000200001. ISSN 0074-0276. PMID 18425263. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762008000200001&lng=en&nrm=iso&tlng=en.
7. ^ Létourneau S, Im EJ, Mashishi T, et al. (Oct 2007). "Design and pre-clinical evaluation of a universal HIV-1 vaccine". PLoS ONE 2 (10): e984. doi:10.1371/journal.pone.0000984. PMID 17912361. PMC 1991584. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000984.
8. ^ Poignard P, Sabbe R, Picchio GR, et al. (April 1999). "Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo". Immunity 10 (4): 431–8. doi:10.1016/S1074-7613(00)80043-6. ISSN 1074-7613. PMID 10229186.
9. ^ Berman PW, Gregory TJ, Riddle L, et al. (June 1990). "Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160". Nature 345 (6276): 622–5. doi:10.1038/345622a0. ISSN 0028-0836. PMID 2190095.
10. ^ Connor RI, Korber BT, Graham BS, et al. (February 1998). "Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines". Journal of virology 72 (2): 1552–76. ISSN 0022-538X. PMID 9445059. PMC 124637. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=9445059.
11. ^ Morgan C, Marthas M, Miller C, et al. (August 2008). "The use of nonhuman primate models in HIV vaccine development". PLoS Med. 5 (8): e173. doi:10.1371/journal.pmed.0050173. ISSN 1549-1277. PMID 18700814. PMC 2504486. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050173.
12. ^ Marques, R.; Williams, A.; Eksmond, U.; Wullaert, A.; Killeen, N.; Pasparakis, M.; Kioussis, D.; Kassiotis, G. (2009). "Generalized immune activation as a direct result of activated CD4+ T cell killing". Journal of Biology 8 (10): 93. doi:10.1186/jbiol194. PMID 19943952. edit
13. ^ Vrisekoop, N.; Mandl, J. N.; Germain, R. N. (2009). "Life and death as a T lymphocyte: from immune protection to HIV pathogenesis". Journal of Biology 8 (10): 91. doi:10.1186/jbiol198. PMID 19951397. edit
14. ^ "STEP Study Locations". http://www.stepstudies.com/new/locations.shtml. Retrieved 2008-11-04.
15. ^ Sekaly, R. P. (2008). The failed HIV Merck vaccine study: a step back or a launching point for furture vaccine development? Journaly of Cell Biology, 205, (1), 7-12
16. ^ Timberg, Craig (2007-10-25). "AIDS vaccine may have raised risk of infection". The Washington Post. http://seattletimes.nwsource.com/html/health/2003973431_aids25.html. Retrieved 2007-11-12.
17. ^ Sekaly RP (January 2008). "The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development?". J. Exp. Med. 205 (1): 7–12. doi:10.1084/jem.20072681. ISSN 0022-1007. PMID 18195078. PMC 2234358. http://www.jem.org/cgi/pmidlookup?view=long&pmid=18195078.
18. ^ Song, Kyung M.; Ostrom, Carol M. (2007-11-08). "Failure of AIDS vaccine punctures soaring hopes". Seattle Times. http://seattletimes.nwsource.com/html/health/2004001162_stepvaccine08m.html. Retrieved 2008-10-29.
19. ^ Iaccino E, Schiavone M, Fiume G, Quinto I, Scala G (Jul 2008). "The aftermath of the Merck's HIV vaccine trial". Retrovirology 5: 56. doi:10.1186/1742-4690-5-56. PMID 18597681. PMC 2483718. http://www.retrovirology.com/content/5//56.
20. ^ a b Harmon, Katherine (16 November 2009). "Renewed Hope". Scientific American (Scientific American, Inc.) 302 (1): pp. 15–16. January 2010. doi:10.1038/scientificamerican0110-15. ISSN 0036-8733. Archived from the original on 23 December 2009. http://www.webcitation.org/5mEyGfWsP. Retrieved 23 December 2009
21. ^ Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. (November 2009). "Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand". N. Engl. J. Med. 361 (23): 2209–2220. doi:10.1056/NEJMoa0908492. PMID 19843557. Archived from the original on 23 December 2009. http://www.webcitation.org/5mEyyRZ06.
22. ^ "Tracking Funding for Preventive HIV Vaccine Research & Development: Estimates of Annual Investments and Expenditures 2000 to 2005". http://www.iavi.org/publications-resources/Pages/PublicationDetail.aspx?pubID=1251. Retrieved 2009-01-10.
23. ^ "SSRN-Advanced Purchase Commitments for a Malaria Vaccine: Estimating Costs and Effectiveness by Ernst Berndt, Rachel Glennerster, Michael Kremer, Jean Lee, Ruth Levine, Georg Weizsacker, Heidi Williams". http://papers.ssrn.com/sol3/papers.cfm?abstract_id=696741. Retrieved 2009-01-10.
24. ^ Nabel, G. J. (2001). "Challenges and opportunities for development of an AIDS vaccine". Nature 410 (6831): 1002–1007. doi:10.1038/35073500. PMID 11309631 .
25. ^ "Human trials approval sought for AIDS vaccine". http://communications.uwo.ca/com/western_news/stories/human_trials_approval_sought_for_aids_vaccine_20090630444536/. Retrieved 2009-06-30.
External links
* Vaccine Research Center (VRC)- Information concerning Preventive HIV vaccine research studies
* NIAID HIV vaccine site (DAIDS)
* Global Alliance for Vaccines and Immunization (GAVI)
* International AIDS Vaccine Initiative (IAVI)
* AIDS Vaccine Advocacy Coalition (AVAC)
* U.S. Military HIV Research Program (MHRP)
* The Pipeline Project - Vaccines in Development (Center for HIV Information at the University of California San Francisco and the HIV Vaccine Trials Network)
* Capital Area Vaccine Effort (CAVE
* Investigation of first candidate vaccine
* Vaccines for Development
* Be the Generation - Information on HIV Vaccine Clinical Research in 20 American Cities
* Australian recruiter for HIV treatment studies
* Aids Vaccine Integrated Project (European Union research programme)
* AIDS.gov - The U.S. Federal Domestic HIV/AIDS Resource
* HIVtest.org - Find an HIV testing site near you
* [1]
* - HIV vaccine 'reduces infection'
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#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III
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Retrieved from "http://en.wikipedia.org/wiki/HIV_vaccine"
Categories: HIV vaccine research | HIV/AIDS | Vaccines
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An HIV vaccine is the theoretical vaccine which would be given to persons without HIV in order to vaccinate them against getting HIV, the virus which causes AIDS. No effective vaccine against HIV exists. As there is no known cure for AIDS, the search for a vaccine has become part of medical approaches against the disease.
It has been known for many years that HIV is an extremely difficult virus to render harmless, and no cure presently exists. Research into a vaccine is one of several strategies to reduce the worldwide harm from AIDS, with other approaches based upon antiviral treatments such as highly active antiretroviral therapy (HAART), and social approaches such as safe sex.
There is evidence that a vaccine may be possible. Work with monoclonal antibodies (MAb) has proven that the human body can defend itself against HIV, and certain individuals remain asymptomatic for decades after HIV infection. More recently in 2009, a number of potential candidates for antibodies and early stage results from clinical trials have been announced by various teams. However these are early results, and have either not been developed to the point of human testing, or not fully peer reviewed and replicated by other teams, at this time.
Contents
[hide]
* 1 Overview
* 2 Difficulties in developing an HIV vaccine
o 2.1 HIV structure
o 2.2 Animal model
* 3 Clinical trials to date
o 3.1 Phase I
o 3.2 Phase II
o 3.3 Phase III
o 3.4 Planned clinical trials
* 4 Economics of vaccine development
* 5 Future work
* 6 See also
* 7 References
* 8 External links
Overview
The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 25 million people since 1981.[1] Indeed, in 2002, AIDS became the primary cause of mortality due to an infectious agent in Africa.[2]
Alternative medical treatments to a vaccine do exist. Highly active antiretroviral therapy (HAART) has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. HAART allows the stabilization of the patient’s symptoms and viremia, but they do not cure the patient of HIV, nor of the symptoms of AIDS. And, importantly, HAART does nothing to prevent the spread of HIV through people with undiagnosed HIV infections. Safer sex measures have also proven insufficient to halt the spread of AIDS in the worst affected countries, despite some success in reducing infection rates.
Therefore, an HIV vaccine is generally considered as the most likely, and perhaps the only way by which the AIDS pandemic can be halted. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.
[edit] Difficulties in developing an HIV vaccine
In 1984, after the confirmation of the etiological agent of AIDS by scientists at the U.S. National Institutes of Health and the Pasteur Institute, the United States Health and Human Services Secretary Margaret Heckler declared that a vaccine would be available within two years.[citation needed]
However, the classical vaccination approaches that have been successful in the control of various viral diseases by priming the adaptive immunity to recognize the viral envelope proteins have failed in the case of HIV-1. Some have stated that an HIV vaccine may not be possible without significant theoretical advances.[3]
There are a number of factors that cause development of an HIV vaccine to differ from the development of other classic vaccines:[4]
* Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection; there are almost no recovered AIDS patients.
* Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS.
* Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues.
* Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.
* Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract.
HIV structure
The epitopes of the viral envelope are more variable than those of many other viruses. Furthermore, the functionally important epitopes of the gp120 protein are masked by glycosylation, trimerisation and receptor-induced conformational changes making it difficult to block with neutralising antibodies.
The ineffectiveness of previously developed vaccines primarily stems from two related factors.
* First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system, the population of virus in an infected individual typically evolves so that it can evade the two major arms of the adaptive immune system; humoral (antibody-mediated) and cellular (mediated by T cells) immunity.
* Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.
The difficulties in stimulating a reliable antibody response has led to the attempts to develop a vaccine that stimulates a response by cytotoxic T-lymphocytes.[5][6]
Another response to the challenge has been to create a single peptide that contains the least variable components of all the known HIV strains.[7]
[edit] Animal model
The typical animal model for vaccine research is the monkey, often the macaque. Monkeys can be infected with SIV or the chimeric SHIV for research purposes. However, the well-proven route of trying to induce neutralizing antibodies by vaccination has stalled because of the great difficulty in stimulating antibodies that neutralise heterologous primary HIV isolates.[8] Some vaccines based on the virus envelope have protected chimpanzees or macaques from homologous virus challenge,[9] but in clinical trials, individuals who were immunised with similar constructs became infected after later exposure to HIV-1.[10]
There are some differences between SIV and HIV that may introduce challenges in the use of an animal model.[11]
As published on 27 November 2009 in Journal of Biology, there is new animal model strongly resembling that of HIV in humans. Generalized immune activation as a direct result of activated CD4+ T cell killing - performed in mice allows new ways of testing HIV behaviour.[12][13]
[edit] Clinical trials to date
Ambox outdated serious.svg
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Several vaccine candidates are in varying phases of clinical trials.
[edit] Phase I
Most initial approaches have focused on the HIV envelope protein. At least thirteen different gp120 and gp160 envelope candidates have been evaluated, in the US predominantly through the AIDS Vaccine Evaluation Group. Most research focused on gp120 rather than gp41/gp160, as the latter are generally more difficult to produce and did not initially offer any clear advantage over gp120 forms. Overall, they have been safe and immunogenic in diverse populations, have induced neutralizing antibody in nearly 100% recipients, but rarely induced CD8+ cytotoxic T lymphocytes (CTL). Mammalian derived envelope preparations have been better inducers of neutralizing antibody than candidates produced in yeast and bacteria. Although the vaccination process involved many repeated "booster" injections, it was very difficult to induce and maintain the high anti-gp120 antibody titers necessary to have any hope of neutralizing an HIV exposure.
The availability of several recombinant canarypox vectors has provided interesting results that may prove to be generalizable to other viral vectors. Increasing the complexity of the canarypox vectors by inclusion of more genes/epitopes has increased the percent of volunteers that have detectable CTL to a greater extent than did increasing the dose of the viral vector. Importantly, CTLs from volunteers were able to kill peripheral blood mononuclear cells infected with primary isolates of HIV, suggesting that induced CTLs could have biological significance. In addition, cells from at least some volunteers were able to kill cells infected with HIV from other clades, though the pattern of recognition was not uniform among volunteers. Canarypox is the first candidate HIV vaccine that has induced cross-clade functional CTL responses. The first phase I trial of the candidate vaccine in Africa was launched early in 1999 with Ugandan volunteers. The study determined the extent to which Ugandan volunteers have CTL that are active against the subtypes of HIV prevalent in Uganda, A and D.
Other strategies that have progressed to phase I trials in uninfected persons include peptides, lipopeptides, DNA, an attenuated Salmonella vector, lipopeptides, p24, etc. Specifically, candidate vaccines that induce one or more of the following are being sought:
* neutralizing antibodies active against a broad range of HIV primary isolates;
* cytotoxic T cell responses in a vast majority of recipients;
* strong mucosal immune responses.
Phase II
On December 13, 2004, the HIV Vaccine Trials Network (HVTN) began recruiting for the STEP study, a 3,000-participant phase II clinical trial of a novel HIV vaccine, at sites in North America, South America, the Caribbean and Australia.[14] The trial was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is a division of the National Institutes of Health (NIH), and the pharmaceutical company Merck & Co. Merck developed the experimental vaccine called V520 to stimulate HIV-specific cellular immunity, which prompts the body to produce T cells that kill HIV-infected cells. In previous smaller trials, this vaccine was found to be safe, because of the lack of adverse effects on the patients. The vaccine showed induced cellular immune responses against HIV in more than half of volunteers.[1]
V520 contains a weakened adenovirus that serves as a carrier for three subtype B HIV genes (gag / pol / nef). Subtype B is the most prevalent HIV subtype in the regions of the study sites. 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 a weakened adenovirus, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. It was announced in September 2007 that the trial for V520 would be discontinued after it determined that the vaccination was ineffective. The foremost issue facing the rAd5 adenovirus that was used is the high prevalence of the adenovirus-specific antibodies as a result of prior exposure to the virus. Adenovirus vectors and many other viral vectors currently used in HIV vaccines, will induce a rapid memory immune response against the vector. This results in an impediment to the development of a T cell response against the inserted antigen (HIV antigens)[15] Additionally, it appears that V520 may have made some recipients more receptive to infection by HIV-1.[16][17]
The HVTN expected to finish the study in 2009, but ceased further treatment administration and declared the vaccine ineffective at preventing HIV-infection in September 2007.[18] The results of the trial have caused some to call for a reexamination of vaccine development strategies.[19]
[edit] Phase III
In February 2003, VaxGen announced that their AIDSVAX vaccine was a failure in North America as there was not a statistically significant reduction of HIV infection within the study population. This same vaccine was retested in Thailand within a vaccine regimen called RV 144 beginning in 2003, with positive results. In both cases the vaccines targeted gp120 and were specific for the geographical regions. The Thai trial was the largest AIDS vaccine trial to date when it started.[20]
In October 2009, the results of the RV 144 trial were published. Initial results, released in September 2009 prior to publication of complete results, were encouraging for scientists in search of a vaccine. The study involved 16,395 participants who did not have HIV infection, 8197 of whom were given treatment consisting of two experimental vaccines targeting HIV types B and E that are prevalent in Thailand, while 8198 were given a placebo. The participants were tested for HIV every six months for three years. After three years, the vaccine group saw HIV infection rates reduced by more than 30% compared with those in the placebo group. However, after taking into account the seven people who had HIV infections at the time of their vaccination (two in the placebo group, five in the vaccine group) the percentage dropped to 26%. [20][21]
[edit] Planned clinical trials
Novel approaches, including modified vaccinia Ankara (MVA), adeno-associated virus, Venezuelan equine encephalitis (VEE) replicons, and codon-optimized DNA have proven to be strong inducers of CTL in macaque models, and have provided at least partial protection in some models. Most of these approaches are in, or will soon enter, clinical studies.
[edit] Economics of vaccine development
A June 2005 study estimates that $682 million is spent on AIDS vaccine research annually.[22]
Economic issues with developing an AIDS vaccine include the need for advance purchase commitment (or advance market commitments) because after an AIDS vaccine has been developed, governments and NGOs may be able to bid the price down to marginal cost.[23]
[edit] Future work
According to Gary J. Nabel of the Vaccine Research Center in Bethesda, Maryland, several hurdles must be overcome before scientific research will culminate in a definitive AIDS vaccine.[24] First, greater translation between animal models and human trials must be established. Second, new, more effective, and more easily produced vectors must be identified. Finally, and most importantly, there must arise a robust understanding of the immune response to potential vaccine candidates. Emerging technologies that enable the identification of T-cell-receptor specificities and cytokine profiles will prove invaluable in hastening this process.
A study that has had success in animal subjects is about to begin human trials in London, Ontario.[25]
[edit] See also
* HIV Vaccine Trials Network
* Subunit HIV vaccine
* World AIDS Vaccine Day
References
1. ^ a b Joint United Nations Programme on HIV/AIDS (UNAIDS) (December 2005). "AIDS epidemic update" (PDF). World Health Organization. http://www.unaids.org/html/pub/publications/irc-pub06/epi_update2005_en_pdf.pdf. Retrieved 2006-01-20.
2. ^ UNAIDS (2004) Report on the global AIDS epidemic, July 2004
3. ^ Watkins DI (Mar 2008). "Basic HIV Vaccine Development". Top HIV Med 16 (1): 7–8. ISSN 1542-8826. PMID 18441377. http://www.iasusa.org/pub/topics/2008/issue1/7.pdf.
4. ^ A. S. Fauci, 1996, An HIV vaccine: breaking the paradigms, Proc. Am. Assoc. Phys. 108:6.
5. ^ Kim D, Elizaga M, Duerr A (March 2007). "HIV vaccine efficacy trials: towards the future of HIV prevention". Infect. Dis. Clin. North Am. 21 (1): 201–17, x. doi:10.1016/j.idc.2007.01.006. ISSN 0891-5520. PMID 17502236. http://linkinghub.elsevier.com/retrieve/pii/S0891-5520(07)00008-6.
6. ^ Watkins DI (March 2008). "The hope for an HIV vaccine based on induction of CD8+ T lymphocytes--a review". Mem. Inst. Oswaldo Cruz 103 (2): 119–29. doi:10.1590/S0074-02762008000200001. ISSN 0074-0276. PMID 18425263. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762008000200001&lng=en&nrm=iso&tlng=en.
7. ^ Létourneau S, Im EJ, Mashishi T, et al. (Oct 2007). "Design and pre-clinical evaluation of a universal HIV-1 vaccine". PLoS ONE 2 (10): e984. doi:10.1371/journal.pone.0000984. PMID 17912361. PMC 1991584. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000984.
8. ^ Poignard P, Sabbe R, Picchio GR, et al. (April 1999). "Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo". Immunity 10 (4): 431–8. doi:10.1016/S1074-7613(00)80043-6. ISSN 1074-7613. PMID 10229186.
9. ^ Berman PW, Gregory TJ, Riddle L, et al. (June 1990). "Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160". Nature 345 (6276): 622–5. doi:10.1038/345622a0. ISSN 0028-0836. PMID 2190095.
10. ^ Connor RI, Korber BT, Graham BS, et al. (February 1998). "Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines". Journal of virology 72 (2): 1552–76. ISSN 0022-538X. PMID 9445059. PMC 124637. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=9445059.
11. ^ Morgan C, Marthas M, Miller C, et al. (August 2008). "The use of nonhuman primate models in HIV vaccine development". PLoS Med. 5 (8): e173. doi:10.1371/journal.pmed.0050173. ISSN 1549-1277. PMID 18700814. PMC 2504486. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050173.
12. ^ Marques, R.; Williams, A.; Eksmond, U.; Wullaert, A.; Killeen, N.; Pasparakis, M.; Kioussis, D.; Kassiotis, G. (2009). "Generalized immune activation as a direct result of activated CD4+ T cell killing". Journal of Biology 8 (10): 93. doi:10.1186/jbiol194. PMID 19943952. edit
13. ^ Vrisekoop, N.; Mandl, J. N.; Germain, R. N. (2009). "Life and death as a T lymphocyte: from immune protection to HIV pathogenesis". Journal of Biology 8 (10): 91. doi:10.1186/jbiol198. PMID 19951397. edit
14. ^ "STEP Study Locations". http://www.stepstudies.com/new/locations.shtml. Retrieved 2008-11-04.
15. ^ Sekaly, R. P. (2008). The failed HIV Merck vaccine study: a step back or a launching point for furture vaccine development? Journaly of Cell Biology, 205, (1), 7-12
16. ^ Timberg, Craig (2007-10-25). "AIDS vaccine may have raised risk of infection". The Washington Post. http://seattletimes.nwsource.com/html/health/2003973431_aids25.html. Retrieved 2007-11-12.
17. ^ Sekaly RP (January 2008). "The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development?". J. Exp. Med. 205 (1): 7–12. doi:10.1084/jem.20072681. ISSN 0022-1007. PMID 18195078. PMC 2234358. http://www.jem.org/cgi/pmidlookup?view=long&pmid=18195078.
18. ^ Song, Kyung M.; Ostrom, Carol M. (2007-11-08). "Failure of AIDS vaccine punctures soaring hopes". Seattle Times. http://seattletimes.nwsource.com/html/health/2004001162_stepvaccine08m.html. Retrieved 2008-10-29.
19. ^ Iaccino E, Schiavone M, Fiume G, Quinto I, Scala G (Jul 2008). "The aftermath of the Merck's HIV vaccine trial". Retrovirology 5: 56. doi:10.1186/1742-4690-5-56. PMID 18597681. PMC 2483718. http://www.retrovirology.com/content/5//56.
20. ^ a b Harmon, Katherine (16 November 2009). "Renewed Hope". Scientific American (Scientific American, Inc.) 302 (1): pp. 15–16. January 2010. doi:10.1038/scientificamerican0110-15. ISSN 0036-8733. Archived from the original on 23 December 2009. http://www.webcitation.org/5mEyGfWsP. Retrieved 23 December 2009
21. ^ Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. (November 2009). "Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand". N. Engl. J. Med. 361 (23): 2209–2220. doi:10.1056/NEJMoa0908492. PMID 19843557. Archived from the original on 23 December 2009. http://www.webcitation.org/5mEyyRZ06.
22. ^ "Tracking Funding for Preventive HIV Vaccine Research & Development: Estimates of Annual Investments and Expenditures 2000 to 2005". http://www.iavi.org/publications-resources/Pages/PublicationDetail.aspx?pubID=1251. Retrieved 2009-01-10.
23. ^ "SSRN-Advanced Purchase Commitments for a Malaria Vaccine: Estimating Costs and Effectiveness by Ernst Berndt, Rachel Glennerster, Michael Kremer, Jean Lee, Ruth Levine, Georg Weizsacker, Heidi Williams". http://papers.ssrn.com/sol3/papers.cfm?abstract_id=696741. Retrieved 2009-01-10.
24. ^ Nabel, G. J. (2001). "Challenges and opportunities for development of an AIDS vaccine". Nature 410 (6831): 1002–1007. doi:10.1038/35073500. PMID 11309631 .
25. ^ "Human trials approval sought for AIDS vaccine". http://communications.uwo.ca/com/western_news/stories/human_trials_approval_sought_for_aids_vaccine_20090630444536/. Retrieved 2009-06-30.
External links
* Vaccine Research Center (VRC)- Information concerning Preventive HIV vaccine research studies
* NIAID HIV vaccine site (DAIDS)
* Global Alliance for Vaccines and Immunization (GAVI)
* International AIDS Vaccine Initiative (IAVI)
* AIDS Vaccine Advocacy Coalition (AVAC)
* U.S. Military HIV Research Program (MHRP)
* The Pipeline Project - Vaccines in Development (Center for HIV Information at the University of California San Francisco and the HIV Vaccine Trials Network)
* Capital Area Vaccine Effort (CAVE
* Investigation of first candidate vaccine
* Vaccines for Development
* Be the Generation - Information on HIV Vaccine Clinical Research in 20 American Cities
* Australian recruiter for HIV treatment studies
* Aids Vaccine Integrated Project (European Union research programme)
* AIDS.gov - The U.S. Federal Domestic HIV/AIDS Resource
* HIVtest.org - Find an HIV testing site near you
* [1]
* - HIV vaccine 'reduces infection'
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virs (prot)
cutn/syst (hppv, hiva, infl, zoon), epon
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#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III
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Retrieved from "http://en.wikipedia.org/wiki/HIV_vaccine"
Categories: HIV vaccine research | HIV/AIDS | Vaccines
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Major Prevention Therapy for HIV in Women Found
Major Prevention Therapy for HIV in Women Found
Scientists yesterday reported a major stride towards a vaginal gel that can thwart HIV, a goal that would be of huge benefit to African women bearing the brunt of the AIDS pandemic.
AFP news agency reported that the proto type cream tested in South Africa reduced the risk of infection by the human immunodeficiency virus (HIV) by 39 percent overall, but by 54 per cent among those women who used it most consistently, they said.
The study coincided with the six-day 18th International AIDS Conference, which opened in Vienna on Sunday.
The results must now be validated in a third, wider phase in the arduous process of assessing a new medication for safety and effectiveness.
Although several questions have yet to be answered, the findings are a bright ray of hope in the 29-year campaign against acquired immunodeficiency syndrome (AIDS), the researchers said.
“Without this gel, we may see 10 women becoming infected in a year. With this gel, we would see only six women becoming infected,” said Salim Abdool Karim, one of the two leading co-researchers, in a teleconference with reporters. Twenty-five million people have been slain by AIDS today and more than 33 million others today are infected by HIV, which causes the disease.
More than two-thirds of these live in sub-Saharan Africa, where 60 per cent of new infections occur among women and girls. One of the big vectors of transmission is through coercive intercourse by an infected partner who is unwilling to wear a condom.
It is a frontline component in the “cocktail” of antiretroviral drugs that disrupt HIV reproduction in immune cells.
Previous microbicide that have been tested have not contained an antiretroviral, and have had either a very low level of protection or even boosted the risk of infection.
Over nearly three years, the gel was tested among 445 HIV-negative women, while 444 counterparts received a harmless lookalike called a placebo. They were then tested for HIV at monthly follow-up visits, where they were also given counseling in safe sex, access to condoms and treatment for sexually-transmitted disease. Each participant was asked to insert, using a vaginal applicator, a first dose of the gel within 12 hours before sex followed by a second dose as soon as possible but within 12 hours afterwards, said co-leader Quarraisha Abdool Karim, also of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban. Compared to the placebo group, the gel reduced the risk of HIV infection by 39 percent overall, but by 54 percent among women who adhered to the instructions most faithfully.
There was no increase in side effects, nor -- among women who became infected with HIV any sign that they were more resistant to tenofovir as a result of the gel. Despite this good news, the scientists said they still had to tackle several important issues. One is why the gel seemed to be less effective after about 18 months. This may be due to weakened adherence to the cream, they suggested. About 40 percent of the women in the trial used the microbicide less than one time out of two. The trial was conducted in an urban setting (Durban) and a rural setting (Pietermaritzburg) KwaZulu-Natal province, enrolling sexually active women aged 18 to 40 considered to be of high risk of exposure to HIV.
It was a so-called IIb trial, meaning that it had passed earlier scrutiny for safety and effectiveness, but was still relatively small compared to a Phase III test involving several thousand volunteers. The study, published by the US journal, Science, was to be the focus of a seminar on Wednesday at the world AIDS forum. If eventually the gel is approved for use, it will join a small but growing arsenal of preventative tools against HIV. For a long time, the condom was the only method that had a confirmed high degree of protection from HIV in intercourse. Four years ago, it was joined by male circumcision. Removal of the foreskin, which contains cells that are vulnerable to penetration by HIV, can reduce HIV risk by more than half, but only for men and not for women. Availability of a microbicide that is 60 percent effective would avert two and a half million infections over three years, according to a2003 mathematical study.
Scientists yesterday reported a major stride towards a vaginal gel that can thwart HIV, a goal that would be of huge benefit to African women bearing the brunt of the AIDS pandemic.
AFP news agency reported that the proto type cream tested in South Africa reduced the risk of infection by the human immunodeficiency virus (HIV) by 39 percent overall, but by 54 per cent among those women who used it most consistently, they said.
The study coincided with the six-day 18th International AIDS Conference, which opened in Vienna on Sunday.
The results must now be validated in a third, wider phase in the arduous process of assessing a new medication for safety and effectiveness.
Although several questions have yet to be answered, the findings are a bright ray of hope in the 29-year campaign against acquired immunodeficiency syndrome (AIDS), the researchers said.
“Without this gel, we may see 10 women becoming infected in a year. With this gel, we would see only six women becoming infected,” said Salim Abdool Karim, one of the two leading co-researchers, in a teleconference with reporters. Twenty-five million people have been slain by AIDS today and more than 33 million others today are infected by HIV, which causes the disease.
More than two-thirds of these live in sub-Saharan Africa, where 60 per cent of new infections occur among women and girls. One of the big vectors of transmission is through coercive intercourse by an infected partner who is unwilling to wear a condom.
It is a frontline component in the “cocktail” of antiretroviral drugs that disrupt HIV reproduction in immune cells.
Previous microbicide that have been tested have not contained an antiretroviral, and have had either a very low level of protection or even boosted the risk of infection.
Over nearly three years, the gel was tested among 445 HIV-negative women, while 444 counterparts received a harmless lookalike called a placebo. They were then tested for HIV at monthly follow-up visits, where they were also given counseling in safe sex, access to condoms and treatment for sexually-transmitted disease. Each participant was asked to insert, using a vaginal applicator, a first dose of the gel within 12 hours before sex followed by a second dose as soon as possible but within 12 hours afterwards, said co-leader Quarraisha Abdool Karim, also of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban. Compared to the placebo group, the gel reduced the risk of HIV infection by 39 percent overall, but by 54 percent among women who adhered to the instructions most faithfully.
There was no increase in side effects, nor -- among women who became infected with HIV any sign that they were more resistant to tenofovir as a result of the gel. Despite this good news, the scientists said they still had to tackle several important issues. One is why the gel seemed to be less effective after about 18 months. This may be due to weakened adherence to the cream, they suggested. About 40 percent of the women in the trial used the microbicide less than one time out of two. The trial was conducted in an urban setting (Durban) and a rural setting (Pietermaritzburg) KwaZulu-Natal province, enrolling sexually active women aged 18 to 40 considered to be of high risk of exposure to HIV.
It was a so-called IIb trial, meaning that it had passed earlier scrutiny for safety and effectiveness, but was still relatively small compared to a Phase III test involving several thousand volunteers. The study, published by the US journal, Science, was to be the focus of a seminar on Wednesday at the world AIDS forum. If eventually the gel is approved for use, it will join a small but growing arsenal of preventative tools against HIV. For a long time, the condom was the only method that had a confirmed high degree of protection from HIV in intercourse. Four years ago, it was joined by male circumcision. Removal of the foreskin, which contains cells that are vulnerable to penetration by HIV, can reduce HIV risk by more than half, but only for men and not for women. Availability of a microbicide that is 60 percent effective would avert two and a half million infections over three years, according to a2003 mathematical study.
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