Vaccines against the immunodeficiency virus: from monkeys to humans
VIO vaccinesEgor Voronin
This news has actually been around for five years, and it appeared in the newspapers again due to the fact that the authors published another article in Nature.
At the AIDS Vaccine 2013 conference, held on October 7-10 in Barcelona, two more groups working independently of Picker and comrades received similar data.
The creation of this vaccine was based on the idea that HIV infection should be stopped at the earliest stage, before the virus had time to spread through the body. Conventional vaccines are too slow, by the time the immune memory is activated, the virus is already "gone". We needed a vaccine that would constantly maintain activated lymphocytes in the mucous membranes (where the virus enters the body).
To do this, Picker and company decided to use cytomegalovirus (CMV). This virus belongs to the herpesvirus family and after the initial infection, a latent phase occurs, in which the virus is not completely cleaned out of the body, but hides in cells (usually in neurons) and only sometimes reactivates. Immunity against this virus is interesting because virus-specific lymphocytes constantly circulate through peripheral tissues and are ready to suppress the virus at any time if it tries to get out of the latent stage.
Is it possible to use this method to create similar immunity to HIV?
In Picker's group, a weakened strain of simian CMV was taken and several key proteins of VIO (an analogue of HIV, the monkey immunodeficiency virus) were embedded in it. When they infected macaques with such a chimeric virus, what they expected happened – a latent immune response was produced not only to CMV proteins, but also to VIO proteins.
Infection of these monkeys with VIO through the mucous membranes gave a strange result: in half of the monkeys, the vaccine had no effect at all, in the other half, the virus appeared for a short time, but then the immunity completely suppressed it.
No fundamental difference (genetic or in the immune response) was found between these two groups, so the researchers assumed that this is a random phenomenon: at an early stage of infection (while the virus is still very small and it is concentrated in the mucous tissue), the virus and the immune system are fighting, and who will win this early fight determines the end result.
A recent article showed that this assumption was incorrect. If vaccinated macaques are injected with a large dose of the virus intravenously, the result is exactly the same – half of the macaques do not resist the virus at all, and half – after a short burst of the virus suppresses it completely, so that the virus in them cannot be found even by the most sophisticated methods. All this was quite mysterious and, to be honest, I was inclined to attribute these results to some unique and poorly controlled features of the model used.
Immunologists, by the way, will be interested to know that macaques vaccinated in this way have an extremely unusual immune response – they have CD8 cells that recognize not MHC-I, but MHC-II (Major Histocompatibility Complex, the main histocompatibility complex).
But, as I said, at the conference that just took place, similar data were presented from two other groups that used slightly different models. Firstly, the Ron Desrosiers group showed that if a similar vaccine is made on the basis of another herpesvirus, rhesus monkey rhadinovirus (RRV), then the results are similar – some macaques completely control VIO, and another (smaller) part controls it, but very poorly (at the same time, their immune response is different than the observed one Picker). Secondly, the Kelly MacDonald group showed that if a similar vaccine is made on the basis of the chickenpox virus (also belonging to the herpesvirus family), then some macaques (in this case, a fairly small part of them) they also completely suppress VIO.
The fact that similar results are obtained in different models is very encouraging. Although there is still a possibility that these are some features of either the immune system of macaques, or the strain of VIO used (which was the same in all three experiments).
Naturally, now all three groups are working feverishly to be the first to experience such an approach in people.
Although the results of Kelly McDonald's group were the least impressive, they are closest to the clinic, because a vaccine based on a weakened version of the virus has long been used against chickenpox, which means that a large amount of information has been accumulated about the safety of using such viruses in humans.
Picker's results are better, but the situation is more complicated – his vaccine is based on the cytomegalovirus of monkeys. There is no vaccine for human CMV, although it is generally considered safe – about half of the population in developed countries are infected with it and have no symptoms.
Derozier has the best results, but the path to the clinic is the most difficult – he uses the monkey herpesvirus RRV, and his closest relative in humans, KSHV (Kaposi sarcoma herpesvirus, aka human herpes virus type 8, HHV-8), although usually harmless, but causes cancer in people with reduced immunity.
In general, all this looks quite encouraging, although so far it's all in monkeys and there is no easy way to transfer these discoveries to humans. Now these vaccines are being tested in monkeys as therapeutic, to control the virus after infection. If they work, then it will probably be the most logical way for their development – to start using them in already infected people and, if they turn out to be effective and safe, then move on to vaccinations of healthy people.
All presentations can be viewed and listened to on the conference website.
Portal "Eternal youth" http://vechnayamolodost.ru18.10.2013