Renewed hope for HIV vaccine, new developments
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Reported by Jules Levin
Durban 2016 July 18-22
A new study set to start in South Africa this year could lead to a licensed HIV vaccine in less than 10 years - the first preventive HIV vaccine worldwide, according to Dr Larry Corey, who is the principle investigator for the trial.
"HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa - the first preventive HIV vaccine worldwide."
The original RV144 vaccine reduced the HIV infection rate among study participants in Thailand by 31 per cent over 3.5 years......the study builds on the only HIV vaccine to show efficacy to date - the RV144 regimen which reduced HIV infection rates in Thai volunteers by 31% over three and a half years, announced in 2009.She predicts HVTN 702 to achieve a 50% reduction - significantly higher than the Thai candidate. "The HIV vaccine field is open for business," she said.
Interim results from HVTN 100 provided the green light for a Phase III efficacy trial on the modified RV144 regimen although criteria for the go-ahead centred on the percentage of HVTN 100 vaccine-recipients who displayed a range of immune responses, and the strength of those responses.
HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa - the first preventive HIV vaccine worldwide," said Corey.
'The HIV vaccine field is open for business,' said Fred Hutch's Dr. Larry Corey at International AIDS Society's biennial meeting in Durban, South Africa
New HIV vaccine for South Africans
From November, 5400 South Africans will begin testing an HIV vaccine designed specifically for South Africans.
The vaccine - a modified version of the Thai vaccine RV144 which showed it can reduce chances of HIV infection by 30% - will be tested on 5 400 HIV-negative men and women across 15 sites in South Africa.
This was revealed by Linda-Gail Bekker - the Deputy Director of the Desmond Tutu HIV Centre in Cape Town and President-Elect of the International AIDS Society - at the International Aids conference in Durban today.
Bekker, who was the protocol chairperson of the HVTN 100 trial, which looked at the safety and tolerability of the Thai vaccine among South Africans, said the vaccine showed good levels of immune responses among South Africans.
She explained that the "HVTN 100 used the same vaccines that RV144 tested, but made them specific to the Clade C subtype of HIV, which is widespread in southern Africa."
"We also changed the adjuvant used with one of the vaccines, with the goal of eliciting a more powerful immune response, and added a booster injection to prolong the period of protection. All the criteria were met unequivocally and, in many instances, the HVTN 100 outcomes exceeded both our own criteria and the immune responses seen in RV144," she said.
The large-scale local trial will be named HVTN 702 and participants will receive five injections over the course of a year. Follow-ups will be made over two years to establish whether the vaccine elicits a sustained protective effect.
The trial will also seek to confirm earlier findings from HVTN 100 that the modified RV144 regimen is safe.
Larry Corey, HVTN principal investigator, said: "It is gratifying to see vaccines that were designed and manufactured specifically for South Africa meet and even exceed the criteria established to advance them into the large efficacy trial."
"HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa - the first preventive HIV vaccine worldwide," he said.
Renewed hope for halting HIV through vaccine
At International AIDS Conference, researchers are optimistic as two new HIV vaccine trials are set to explore different approaches for protection
- Fauci described the decades-long quest to develop an HIV vaccine as "scientifically one of the most difficult challenges that we have ever faced." HIV attacks the very immune cells used in defending the body against it and mutates rapidly within individuals and across geographical locations, making it a moving target for vaccines.
- Scientists give go-ahead for what could become the first licensed vaccine against the AIDS virus....An experimental HIV vaccine regimen being tested in a small clinical trial in South Africa has met the benchmarks to expand into a large-scale trial that could lead to the first licensed vaccine against the virus that causes AIDS, health officials said today......The smaller trial, which began in February 2015 and involves 252 volunteers, is testing the vaccine regimen for safety and to see whether it elicits the predicted immune responses. It is ongoing but was designed to give researchers early feedback. The upcoming large-scale trial is scheduled to launch in November and involve 5,400 HIV-uninfected men and women in South Africa. It will test for efficacy, or whether the vaccine actually protects those who receive it from becoming infected with HIV.Results are expected in late 2020 -39 years after the first cases of AIDS were reported and 37 years after HIV was identified as the virus that causes AIDS.
- The HVTN will roll out a second large-scale trial in South Africain November with 5,400 HIV-negative men and women, the first such trial to be in the field in a decade and one that could lead to the first licensed vaccine against HIV.
- Fauci is convinced that broadly neutralizing antibodies will play an important, but not necessarily exclusive, role in a potential HIV vaccine....The larger trial, called HVTN 702, will be led by Dr. Glenda Gray
Two paths to a vaccine
Even as it plans the rollout of HVTN 702 later this year, the HVTN - the largest global network striving to develop vaccines to prevent HIV -has begun investigating a second path to an HIV vaccine. Partnering with a sister network, the HIV Prevention Trials Network, it launched a clinical trial last month on an approach called antibody mediated prevention, or AMP. Two parallel AMP clinical trials will eventually involve more than
4,000 participants in the United States, South America and southern Africa.
Rather than delivering a vaccine, the AMP trial will use an intravenous infusion, or IV, to deliver so-called broadly neutralizing antibodies (or a placebo) to trial participants. Such antibodies are considered the "holy grail" of HIV vaccine researchers because they could potentially protect people from infection by almost all strains of the virus. But so far, no one has figured out how to make a vaccine that induces them. (The experimental vaccine regimen tested in Thailand and the modified version being tested in South Africa elicit antibodies, but they are not broadly neutralizing.)
If the experimental antibodies being tested in the AMP trial provide protection as hoped, information gleaned from the study could help scientists figure out how to reverse-engineer a vaccine to elicit the antibodies at the concentrations needed.
Fred Hutch's Dr. Larry Corey, HVTN founder and director, believes that the path to the promised land of a vaccine that is 80 percent to 90 percent effective may well end up combining both approaches.
Renewed hope for halting HIV through vaccine
July 19, 2016
By Mary Engel / Fred Hutch News Service
"The pathway to HIV vaccine will be full of surprises," predicted Dr. Anthony Fauci at the International AIDS Conference in Durban, South Africa on Tuesday.
Photo by Robert Hood / Fred Hutch News Service
Editor's note: Fred Hutch News Service reporter Mary Engel and photographer Robert Hood are in Durban, South Africa,covering the newsfrom the 21st International AIDS Conference.
DURBAN, South Africa - Dr. Albert Sabin, developer of the oral live virus polio, once told Dr. Anthony Fauci, "Tony, I do not think we will ever have an HIV vaccine."
As a physician, Fauci, the long-time director of the National Institute of Allergies and Infectious Diseases, part of the U.S. National Institutes of Health, had cared for Sabin in his last days. As a friend, he had delivered the eulogy when Sabin died at age 86 in 1993.
But as a scientist, he completely disagreed with one of the preeminent figures in medical history.
"As much as I loved him, my dear friend Albert Sabin will be proven to be incorrect - one of the very, very few times that Albert ever was wrong," Fauci told a conference hall packed with scientists on Tuesday at the biennial meeting of the International AIDS Society in Durban, South Africa.
Fauci has reason to be optimistic. As the AIDS 2016 conference got underway, the NIAID-funded HIV Vaccine Trials Network, or HVTN, based at Fred Hutchinson Cancer Research Center, was gearing up to launch a large-scale trial in South Africa in November, the first such trial to be in the field in a decade and one that could lead to the first licensed vaccine against HIV.
And within the last few months, the HVTN, working with its sister network, theHIV Prevention Trials Network, or HPTN, based in Durham, North Carolina, has begun what is already being called alandmark studyto test an experimental, so-called broadly neutralizing antibody that could potentially protect people from infection by almost all strains of the rapidly mutating virus that causes AIDS.
That these two different approaches are underway at the same time is a testament to the challenge that Sabin alluded to in finding an HIV vaccine - but also to Fauci's optimism, albeit an optimism tempered by scientific skepticism.
"The pathway to HIV vaccine," he predicted, "will be full of surprises."
Building on the so-called Thai vaccine
The first surprise came in 2009 when, after years of failed attempts, the first sign that an HIV vaccine was even possible came with the publication of clinical trial results of the so-called Thai vaccine, a two-vaccine regimen named after the country in which it was tested. Those who received that regimen had a 31 percent lower risk of becoming infected with HIV 3½ years after vaccination compared to placebo recipients. Although not enough protection to warrant licensing, the results were widely hailed as a breakthrough.
The protection provided by the Thai vaccine took years of study to understand.
In developing a vaccine, Fauci explained, vaccinologists typically try to mimic how the body responds to natural infections. Historically, for almost any viral infection, even the most toxic, those who survived did so because their immune systems ultimately cleared the virus - polio, smallpox, measles, mumps - and left them with immunity to that pathogen. Ever since the first vaccine - against smallpox - was developed in 1796, vaccinologists have sought to mimic that natural response.
But no one has ever cleared HIV naturally and been left with natural immunity. There was no example to mimic.
For years, no experimental vaccines provided any protection. Then came the surprising, if modest, protection achieved by the Thai vaccine, which allowed scientists for the first time to identify "correlates of protection," or early signs of whether a vaccine might be effective. Those correlates helped establish benchmarks for a second trial, this time of a regimen altered to be more protective, longer lasting and effective against the predominant HIV subtype in South Africa, which has the largest HIV epidemic in the world.
Dr. Linda-Gail Bekker, Dr. Glenda Gray and Dr. Larry Corey speak on a panel about HIV vaccine work at the International AIDS Conference Tuesday.
Photo by Robert Hood / Fred Hutch News Service
In May, NIAID and the HVTN announced that a small, early-phase trial met those markers and gave the go-ahead to expand into a larger trial, conducted in South Africa, which could lead to a licensed vaccine. The goal is to reach at least 50 percent protection via a more potent, longer-lasting vaccine.
"We hope to have results in five years," said Dr. Glenda Gray, president of theSouth African Medical Research Council, who as a principal investigator for the HVTN is leading the trial. "It's going to be a very exciting five years for all of us. It's the result of many, many, many years of hard work from basic scientists to clinicians to our trial volunteers."
A second path
In the meantime, on a parallel track, scientists who spent years studying people with HIV had come across some who developed the broadly neutralizing antibodies that are considered the holy grail of vaccine research. The trouble is, they developed them too late to protect against infection. So scientists decided to try to work backward: find the antibodies, then try to develop a vaccine to induce them.
But first, they need to make sure the antibodies actually work against HIV. That is what the second trial is designed to find out. Skipping the vaccine step for now, it will deliver a laboratory-produced version of a broadly neutralized antibody directly via an intravenous infusion, or IV.
"I think we will move the HIV vaccine search forward and we will have an HIV vaccine," said Dr. Nyaradzo Mgodi.
Robert Hood / Fred Hutch News Service
Called AMP for Antibody Mediated Prevention, the trial will be the first to test such an antibody against HIV infection in a large clinical trial. At a presentation on HIV vaccines at AIDS 2016, Dr. Nyaradzo Mgodi of the University of Zimbabwe-University of California San Francisco Collaborative Research Programme in Harare, Zimbabwe and chair of the AMP trial in Africa, called the antibody being tested "promising."
"It has broadly neutralizing capabilities and has shown good safety results in early Phase 1 studies," she said. "I think we will move the HIV vaccine search forward and we will have an HIV vaccine."
Early results of the AMP study should be available by 2018, said Fred Hutch's Dr. Larry Corey, the founder and head of the HVTN, at a press briefing Tuesday.
The AMP study in Africa will enroll 1,500 sexually active women at 15 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. A parallel study will enroll 2,700 men and transgender people who have sex with men at 24 sites in the U.S., Brazil and Peru.
Fauci is convinced that broadly neutralizing antibodies will play an important, but not necessarily exclusive, role in a potential HIV vaccine. Corey, who is chairing the AMP study with HPTN head Dr. Myron Cohen, agrees.
"We are at a very novel place in the HIV vaccine field, where we have this strategy of neutralization and non-neutralization," he said. "In the end, we may find that they both give partial efficacy, and we may need to combine them. But we have come a very long way."
Read more about Fred Hutch's HIV work in South Africa here.
Official press releases
New vigour in HIV vaccine research evident at AIDS 2016
posted on 7/19/2016 2:08:00 PM
Tuesday, 19 July
Pivotal South African study builds on promise of the only HIV vaccine regimen to show efficacy to date; landmark antibody trial now in field; multiple newvaccine approaches beingexplored
Durban, South Africa - Current and forthcoming studies of vaccines to prevent HIV infection have created a new optimism that the long and challenging road to the development of such a vaccine has begun to take some promising turns.Updates on the search for preventive vaccines, presented at the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa, included information on advances in the development of novel vaccines, and in the field of antibody mediated prevention (AMP).
Interim immunology results open the way for the first major HIV vaccine efficacy study in seven years.
Participants at AIDS 2016 heard results from the HVTN 100 study, conducted by the US-based HIV Vaccine Trails Network (HVTN) in partnership with South African research sites.HVTN 100 tested the immune responses of South African study volunteers to a modified version of the RV144 regimen, the only HIV vaccine regimen to show efficacy to date. The original RV144 vaccine reduced the HIV infection rate among study participants in Thailand by 31% over 3.5 years.
"HVTN 100 used the same vaccines that RV144 tested, but made them specific to the Clade C subtype of HIV, which is widespread in southern Africa. We also changed the adjuvant used with one of the vaccines, with the goal of eliciting a more powerful immune response, and added a booster injection to prolong the period of protection," said HVTN 100 Protocol Chair Linda-Gail Bekker, who is also Deputy Director of the Desmond Tutu HIV Centre in Cape Town and International AIDS Society President-Elect.
Interim results from HVTN 100, presented here, provided the green light for a Phase III efficacy trial on the modified RV144 regimen. Criteria for the go-ahead centred on the percentage of HVTN 100 vaccine-recipients who displayed a range of immune responses, and the strength of those responses.
"All the criteria were met unequivocally and, in many instances, the HVTN 100 outcomes exceeded both our own criteria and the immune responses seen in RV144," Bekker concluded.
Larry Corey, HVTN Principal Investigator, elaborated: "It is gratifying to see vaccines that were designed and manufactured specifically for South Africa meet and even exceed the criteria established to advance them into the large efficacy trial. HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa - the first preventive HIV vaccine worldwide."
HVTN 702, a placebo-controlled study, will begin enrolling 5,400 HIV-negative men and women at 15 research sites across South Africa before the end of 2016. Participants will receive five injections over the course of a year and will be followed-up for two years more to establish whether the vaccine elicits a sustained protective effect. The trial will also seek to confirm earlier findings from HVTN 100 that the modified RV144 regimen is safe.
A major difficulty in the field of HIV vaccine development is the extraordinary capacity of HIV to mutate and evade the antibodies that might block it. The identification in a small minority of HIV-positive individuals of broadly neutralizing antibodies (bNAbs), which can neutralize a wide range of HIV variants, led to a flourishing of vaccine-related research focused on how to manufacture bNAbs in the laboratory and how to harness bNAbs to prevent infection in HIV-negative individuals.
A landmark event in this field of research was the start of the first large-scale human trials to evaluate whether a bNAb called VRC01, given by infusion, is effective in preventing HIV acquisition.
⋅ The first of the two studies, HVTN 704/HPTN 085, commenced in March in the United States. It will enrol 2,700 gay men and transgender individuals who have sex with men in the U.S., South America and Europe.
⋅ The second study, HVTN 703/HPTN 081, began in June, 2016 in South Africa and will enrol 1,500 heterosexual women in seven sub-Saharan African countries.
These placebo-controlled trials, jointly referred to as the AMP Studies, are almost identical in design. In addition to establishing the efficacy of bNAbs in preventing HIV infection, the AMP Studies will evaluate the safety and tolerability of the VRC01 infusion, and explore what concentration of the bNAb is required for effective prevention.
Researchers agree that the greatest value of the studies may be the scientific insights they yield for future vaccine development. Laboratory analysis of how bNAbs block HIV's entry into healthy cells has already provided invaluable information for vaccine scientists, and more lessons are likely as the performance of VRC01 is studied in a large human cohort.
Scientists are also exploring the design and development of antigens or immunogens that might stimulate the immune system of HIV-negative individuals to produce bNAbs.
The next major multi-site efficacy trial in the HIV vaccine field is likely to be a test of a vaccine regimen that includes a 'mosaic' immunogen, carrying fragments of HIV from different variants of the virus. Researchers believe that this complex immunogen might be fit for use globally, regardless of the predominant variants in different regions.
Other novel vaccine approaches in development include the exploration of improved vectors, safe viral 'vehicles' that are capable of delivering HIV genes that will trigger protection against HIV, or that may even be able to deliver bNAb genes directly.
The field of vaccine development and testing involves a wide range of scientific research organisations and academic institutions around the world, private sector pharmaceutical companies, clinical research sites and laboratories, and thousands of volunteers who take risks and give of their time to participate in studies.
Progress in the HIV Vaccine Field
Oral talk at conference by Larry Corey, pdf of slide talk attached