Researchers Exchange with Brad Jones
On December 20th 2011, an HIV vaccine candidate being developed by researchers at the University of Western Ontario made headlines. To clarify the nature of this development and to frame it in the bigger picture of the history of HIV vaccine development, the OHTN spoke with Brad Jones, PhD, and OHTN Junior Investigator Development Award Recipient to learn more.
Q: What exactly was the event that triggered media interest on Dec 20, 2011?
A: A team of researchers affiliated with the University of Western Ontario and with Sumagen, a Korean based Pharmaceutical Venture company, gained approval to begin phase I human trials of a type of HIV vaccine that has not been tested before*.
* This is an important step in the development of a potential HIV vaccine which aims to test, in a small number of volunteers, whether or not the vaccine strategy is safe. Of note, however, is that at this point there is no data demonstrating that the vaccine is safe or effective in humans. The media's use of the term 'breakthrough' might have mislead the public, suggesting a scientific breakthrough. What was reported on Dec 20th was a breakthrough in the regulatory red-tape where the UWO team received approval from the FDA to begin testing of their vaccine.
Q: How many potential HIV vaccines have made it to Phase I clinical trials?
A: In the past there have been more than 200 HIV vaccine candidates which have received approval for phase I clinical trial testing. There are presently at least 17 phase I clinical trials ongoing.
Q: What is unique about this new HIV vaccine candidate?
A: The current vaccine candidate aims to test a variation of a vaccine strategy which was essentially taken off of the table early in the HIV epidemic for fears that the approach may be too risky. In this sense, receiving approval to test this vaccine concept is a significant regulatory breakthrough.
Q: How is a vaccine developed?
A: The classical ways to make a vaccine are to take the infectious agent that you want to develop protection against (HIV in this case) and either kill it or weaken ('attenuate') it and administer this to the vaccinee (person receiving the vaccine). The vaccine for cholera is an example of a killed vaccine and that for measles is an example of a weakened vaccine.
Q: Would weakened HIV be an option for vaccine development?
A: In monkey models, vaccination with weakened forms of the monkey version of HIV (called 'SIV') is one of the only effective ways of protecting animals from acquiring SIV infection. This weakened virus approach has been considered unacceptable for humans as the vaccine would actually involve injecting people with live (albeit weakened) HIV, and those people would be infected for life. The idea would be that the weakened HIV would not result in progression to AIDS and would protect the vaccinee from acquiring full-strength HIV - but the risks of the weakened HIV spontaneously mutating to a form which could cause illness are considered simply too great.
Q: So how about using killed HIV for a vaccine?
A: There are two concerns with a killed HIV vaccine - the first is, again, one of safety. This strategy would involve taking HIV virus, killing it in some way (heat, radiation, chemical, etc) and then injecting this into vaccinees. For this to be safe, every HIV virus in every dose of vaccine given around the world would have to be well and truly dead - otherwise there would be the possibility of someone becoming infected with HIV from a vaccine. The other concern is that killed HIV may not be very effective as a vaccine as it is not able to effectively stimulate one of the important arms of the immune system - i.e.: a T-cell response.
Q: How have previous candidates for an HIV vaccine been developed?
A: The approaches to HIV vaccination which have been tried so far have avoided using either killed or inactivated HIV. Instead, researchers have tried to develop vaccines that use synthetic mimics of specific parts of the virus. In these strategies no actual HIV viruses were used to make the vaccine, making it impossible that a person could ever become infected with HIV from getting a vaccine. This is really a big part of the crux of why HIV vaccine development has proven to be so difficult - we have not been able to rely on using HIV virus itself, so instead we've had to, in a way, try to trick the immune system into responding to something that 'looks' like HIV.
Q: How does all of this relate to the news about the vaccine from the University of Western Ontario?
A: Dr. Chil-Yong Kang and his team are taking the approach of both weakening and killing the HIV virus and then giving this to clinical trial participants as a vaccine. Presumably, the idea is that the virus would be killed to an extent to which it's extraordinarily unlikely that a vaccinee would ever become infected with HIV - and to have the additional safety net that, if anyone were to become infected, they would be infected with a highly crippled virus which would not lead to illness.
Q: How will the human trials work?
A: In order to make this strategy more acceptable to the US Food and Drug Administration (FDA), this first set of clinical trials (Phase I) will be conducted in participants who are already HIV-infected (i.e.: weakened and killed HIV will be injected into HIV-positive individuals). There is then a planned progression towards HIV-uninfected subjects, should either of the vaccines (weakened and/or killed HIV) be approved for Phase II testing.
The OHTN thanks Brad Jones, OHTN Junior Investigator Development Award Recipient, for January 2012's Researcher Exchange and invites you to share it with your friends! And don't forget to join the Facebook Group to nominate next month's researcher.