Thursday May 12 2011
The study was in rhesus macaque monkeys
“A vaccine which could completely clear the body of all traces of the Aids virus has been developed,” reported the Daily Mirror. It said that “scientists have successfully controlled the disease in monkeys, raising hopes they may finally conquer the human form.”
This large experimental study was in 67 male rhesus macaque monkeys that were given the monkey form of HIV, called Simian Immunodeficiency Virus (SIV). The vaccine was tested in 24 monkeys, 13 of which showed complete control over the SIV virus. Further analysis showed that 12 of these were still protected after a year. In contrast, macaques that did not get the vaccine continued to show high levels of the virus.
This research has re-ignited debate within the research community that a HIV vaccine for humans may be possible. Experts have called this early research exciting and described it as a breakthrough. The technique will now need to be adapted to see if it can be used in treating HIV.
The researchers and commentators acknowledge that the difficult part will be showing the vaccine is safe and effective in humans. Further development of this vaccine might take several years.
Where did the story come from?
The study was carried out by researchers from several US research Institutes, including the Vaccine and Gene Therapy Institute, the AIDS and Cancer Virus Program, and the International AIDS Vaccine Initiative.
The research was supported by grants and contracts with the National Institute of Allergy and Infectious Diseases; the International AIDS Vaccine Initiative (IAVI) and its donors. These included the Bill & Melinda Gates Foundation-supported Collaboration for AIDS Vaccine Discovery, and the National Cancer Institute.
The study was published in the peer-reviewed science journal Nature.
The media have all identified the key features and importance of this research.
What kind of research was this?
This was primarily animal research in which several groups of rhesus monkeys were given a new vaccine and then infected with a Simian immunodeficiency virus (SIV). The vaccine was engineered to instruct the monkeys’ bodies to produce antigens or proteins that attack SIV, the monkey equivalent of HIV. The immune response, cell counts and viral load (the number of detectable SIV virus particles) of the vaccinated monkeys were then compared with control monkeys that had not been vaccinated.
The researchers explain that although the immune system tries to defend against the AIDS-causing viruses (HIV or SIV) usually a short time after infection, these viruses are good at avoiding host immune systems and are only rarely controlled by immunological mechanisms. This has been a major problem in the development of a vaccine for the condition.
These researchers hoped that the virus might be more vulnerable to the immune system in the first few days after exposure, before it had disseminated through the body. They aimed to develop a vaccine that could prime an early and lasting immune response that targeted the virus before it started to replicate in the body.
This was the underlying theory that this appropriately designed study set out to test.
What did the research involve?
Researchers gave 24 healthy rhesus macaques a vaccine containing a genetically modified form of a type of virus called rhesus cytomegalovirus (RhCMV). The modified virus was called RhCMV/SIV. It was designed to persistently promote the response of immune cells and, after allowing the immune systems of the monkeys time to respond, they then infected them with the SIV virus. Another group of monkeys were given a different vaccination and 28 monkeys acted as unvaccinated controls.
The CMV virus is a common virus found in humans and monkeys, which in healthy people causes only mild illness. The researchers genetically modified the CMV virus to carry antigenic proteins into the monkeys so that it could stimulate an immune response to SIV.
The vaccine worked by stimulating the production of a particular type of blood cell, called "effector memory T-cells", which can remain vigilant in the body long after an infection has abated, providing long-term protection. These cells, a type of T lymphocyte, become ‘experienced’ by having encountered an antigen protein previously by vaccination or infection. At a second encounter with the antigen protein, the effector memory T cells can reproduce rapidly to fight off the infection more quickly.
The researchers produced three types of vaccination schedules to test their theory:
- a group of 12 monkeys were given two immunisations with RhCMV/SIV vectors alone
- a group of 12 monkeys were given RhCMV/SIV vectors followed by another immunisation designed to boost the first vaccination
- a group of nine monkeys were given another experimental vaccine along with the booster as a benchmark
- the fourth group of 28 monkeys were unvaccinated controls
After the vaccination, the researchers waited 59 weeks to give the vaccines time to work and then exposed the monkeys to the SIV virus. They measured the amount of virus in the blood of the monkeys and the T cell responses regularly up to 700 days after infection.
What were the basic results?
Of the 24 monkeys given one of the vaccinations containing RhCMV/SIV vectors (boosted or not), there was complete control against SIV with 13 of the monkeys. The plasma viral load (an indicator of active infection with the virus) was reduced and the SIV-specific T-cell responses increased indicating an immune response.
Further analysis after a year showed that 12 of the 13 monkeys that were protected were still protected a year on. Some of the monkeys had small periods of time where the virus was detectable, but the frequency of these disappeared over time.
How did the researchers interpret the results?
The researchers say that their study demonstrates a previously undescribed form of vaccination to control a highly infectious form of SIV. They say that the early acquired infection is arrested before ‘irreversible establishment of disseminated, progressive infection’.
They add that their CMV vectors illustrate a ‘powerful new approach for HIV/AIDS vaccine development’.
This study has been carefully designed and carried out with care and its findings have been described as a breakthrough by experts in the field. This viral-delivered vaccine appears to have overcome the complications previously experienced in attempts to develop a vaccine for HIV. Nevertheless, in half of the monkeys that were given the vaccine the virus was not lowered to non-detectable levels, showing that further work may be needed to further optimise the vaccine.
Additionally, much more work is needed to develop this technique for potential use in humans. The researchers and commentators acknowledge that the difficult part will be showing the vaccine is safe and effective in humans. As the CMV virus is not itself totally harmless and does cause a number of diseases, especially in people with immune problems, negating or reducing the harm from this live virus will be the first priority.
In addition, viruses and vaccines that work in monkeys may not work in humans. Having said that, the monkey model used for these experiments seems to be the closest and most realistic testing bed for these sorts of vaccine.