Scientists were surprised when they unexpectedly stumbled upon a relatively simple vaccine which blocks infection with SIV – the monkey equivalent of HIV – and stops the spread of the virus in already infected monkeys.

How it works

T-lymphocyte. Image via David Darling.

All efficient vaccines against a viral infection elicit virus-specific neutralizing antibodies and sometimes also cytotoxic T-lymphocytes (CTL) that prevent virus infection or eradicate the virus rapidly after it enters the body. So far, this has proven impossible in the case of HIV, despite huge advancements in the last couple of decades. So far, only one trial out of more than a hundred proved limited efficiency, with modest and short lasting protection.

This vaccine, which was described by researchers as ‘surprising’ and ‘unexpected’ works by stimulating the production of a previously unknown group of CD8 T-cells. T-cells are a type of white blood cells that play a crucial role in the body’s immunity. What HIV (and SIV) does is that it supressess the generation of T-cells, and stops the body from recognizing as a dangerous pathogen. This vaccine stimulates the production of a type of T-cells, while suppressing the production of others; the virus is recognized by the body as a pathogen and the body organizes a much better defense.

“Instead of activating dendritic cells by loading them ex vivo with inactivated HIV, we then investigated possibility of developing a prophylactic anti-SIV vaccine by directly stimulating mucosal dendritic cells in vivo.”, authors write in their study.

The vaccine was  based on a long standing but yet unproven theory that conventional vaccines that rely on stimulating an immune response to a microbe in advance of exposure to it could not work in HIV. The problem that HIV poses compared to other viruses is that it uses the very cells that are supposed to fight against it to reproduce. This means that if the body mounts a blind defense, which is the traditional approach for vaccines, HIV would just use the body’s defenses to reproduce. The trick they used was to make the body recognize HIV, but prevent it from launching a proliferative defense which would be used against it.

The Results

Initially, they started out with 21 monkeys which received the vaccine and 8 monkeys which received the vaccine with Lactobacillus plantarum – a common type of gut bacteria.

15 out of the 29 monkeys were completely protected even 4 years after the vaccine was given! The control group of 26 monkeys who were exposed to SIV were all still infected 4 years after. What’s even more notable is that the researchers administered the vaccine through different ways (rectal, vaginal gel and drink). While some of the monkeys who received the vaccine rectally or vaginally were not resistant to infections, all the monkeys who drank the vaccine with the gut bacteria were protected against future SIV exposure.

To be perfectly honest, scientists weren’t expecting to get such remarkable results. They were mystified to see that doing something as simple as giving inactivated SIV along with a simple probiotic preparation produced such a strong immune-suppressant response, especially as iSIV given by itself produced a more typical immune-stimulant response.

Moving on to humans

The results are so promising that they are immediately planning to move on to humans. So far, two trials are planned – in one, HIV-negative volunteers at low risk of HIV will be given the vaccine to see if it stimulates the same immune- and virus-suppressant responses. In the other one, HIV-positive volunteers on fully-suppressive antiviral therapy will be given the vaccine and then taken off ART six months later if the vaccine prompts the same response.

However, it has to be said that just because a vaccine works in monkeys it doesn’t necessarily mean it will have the same success in humans. We will have to wait for human clinical trials, and that will take quite a while (at least a couple of years); so even if everything works out just fine, we’re still a few years away from an effective HIV vaccine. However, this is exciting news, which may very well turn out to be the AIDS breakthrough we’ve been waiting for. Time and future research will tell.

Journal Reference: Jean-Marie Andrieu, Song Chen2, Chunhui Lai, Weizhong Guo and imageWei Lu. Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+ T-regulatory cells that suppress SIV-positive CD4+ T-cell activation and prevent SIV infection in the macaque model.  Front. Immunol., 30 June 2014 | doi: 10.3389/fimmu.2014.00297

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