Since the end of the last century, there have been a number of HIV vaccines developed and tested.
Over 30 clinical trials of these vaccines have been done to see if they conferred immunity to HIV to those volunteers who agreed to participate in the trials.
To date, none of the trials have shown that any of the vaccines can produce significant immunity in a number of people against infection with HIV.
A study published in The Lancet, a distinguished British medical journal, shows that one of the failed vaccines may have had an unintended consequence.
This paper is a follow-up study to some trials done on a vaccine (Merck Ad5 gag/pol/nef subtype B HIV-1 preventive) performed a few years ago. The trials of this vaccine were stopped when the data showed that it was ineffective. At about the same time, a different trial using the same vaccine, showed that those vaccinated seemed to be contracting HIV at a higher rate than those in the study who were given a placebo.
One trial was done in South Africa, the Phambili (or HTVN 503) study. The other study enrolled volunteers from the Caribbean, the Americas and Australia (the HTVN 502 Step study.)
The vaccine made use of a recombinant (genetically-engineered) adenovirus. Adenoviruses can cause infections of the respiratory system, eyes and gastrointestinal tract in humans. Many cause symptoms of the common cold. The adenovirus was added to the vaccine to make the vaccine more effective in producing immunity in those subjects who were vaccinated. Other adenoviruses have been used in the past and haven’t caused similar problems with increased infections. In this vaccine, rAd5 (recombinant adenovirus type 5) was used.
The Phambili study primarily enrolled heterosexual males and females. In the HTVN 502 Step study, there was a preponderance of men who have sex with men (MSMs) and women at high risk for contracting HIV. Each participant was to receive three injections of the vaccine (or injections of placebo for the controls) spaced several weeks apart. Because the trials were stopped early, very few participants actually got all three injections.
The data from the Step study showed that there was an increased chance for vaccinated participants to contract HIV.
This occurred primarily in the MSM group. The vaccinated MSMs who got infected acquired their infections fairly rapidly after the study began. In the Phambili study, heterosexual men also had a greater risk of getting HIV, but those vaccinated males who got HIV tended to get it later than the Step group, sometimes years later. The men who became infected with HIV, in both groups, had similar risk behaviors (multiple partners, failure to use condoms regularly, etc.) Circumcision status didn’t make a difference. Number of vaccine injections made no difference. In short, there seems to be no good reason that one group of men got HIV later than men in the other group.
And why did the vaccine seem to make those vaccinated more prone to infection with HIV?
The researchers think that somehow the adenovirus that was used as a part of the vaccine somehow made those vaccinated less able to resist infection with HIV. The investigators propose some theories about why this is so, but they are only theories at this point. They feel strongly enough about it that they strongly recommend that this adenovirus not be used again in making any other HIV vaccines.
The outcomes here were definitely unforeseen and unintended. Even with decades of vaccine research, testing in non-human species, carefully designed protocols and safeguards, sometimes things like this happen. It is a major reason why prospective participants in research studies have possible risks explained to them. Institutional review boards (IRBs), akin to ethics committees, need to approve the research before it can be carried out on humans. The IRB looks at how much risk to the subjects might be experience and weighs that against the possible benefits of the research. The IRB acts to minimize harm to and to protect the volunteers who may be enrolled in the trial. The IRB requires that those participating in the study be fully informed about the research. At least as fully informed as they can be.
As seen in this instance, even with good preparation and planning, something terrible and unpredictable happened. Unfortunately, things like this happen, rarely, but they do happen. It’s a reminder that research doesn’t always have a good outcome.
Even from this negative result, we may get some benefit. For example, did the rAd5 virus allow the infections to occur? If so, what is the mechanism? If the method that the virus uses to facilitate infection can be identified, that could be an important point. Perhaps we could use that information in reverse and thereby strengthen the cell to make it much more resistant to infection by HIV.
Of course, that would require more research – and risks.