Since the early days of its epidemic, the virus itself has confounded researchers, who have long been searching for a vaccine to prevent its spread. And after years of slow progress, that search may soon be over.
The epidemic as we know it is thought to have started in the mid-to-late 1970s, but it wasn’t until 1983 that the HIV virus was first identified and isolated. By that point, HIV had begun rapidly spread around the world — and since the epidemic began, it’s claimed the lives of over 32 million people.
To understand why this virus causes so much harm, we first need to know how it invades the body.
First off, it’s a retrovirus, which is a type of virus that inserts a copy of its genome into the DNA of a host cell — in HIV’s case, T-helper cells which help our immune system fight off infection. After latching onto the cell, HIV fuses with it, integrating its genetic information with the new host’s DNA. The infected cell then produces more HIV proteins, which are eventually released into the bloodstream where they continue to replicate.
If left untreated, HIV severely weakens the immune system's ability to function properly — this final stage of the infection is AIDS. And it’s precisely the virus's unique characteristic which allows it to propagate inside the human body that also makes it so difficult to tackle.
HIV is a remarkably small virus. It has few genes comprised in it, regardless of how small and simple it may be, it has very complex dynamic interactions with the human immune systems.
There are currently a few ways to stop HIV from progressing in its life cycle. Specific drugs have been developed that can stop the virus from attaching to T-helper cells, which other types of drugs work to prevent the virus from taking control of the cell’s nucleus and enter the bloodstream. Called antiretroviral therapy, or ART, this drug combination works well, but is expensive and requires lifelong upkeep.
“In those resource-constrained areas or where the stigma of HIV is still a major problem, prevention methods that require daily pills may still limit the number of individuals who would have access to there. It’s only through the application of very highly effective vaccines that we have been able to control an infection that spread around the globe, and eventually eradicate that.”
But that doesn’t mean developing a vaccine is easy. There aren’t many good models to reference for research in humans, which means we don’t know what the body’s immune response looks like when trying to protect itself.
HIV’s extraordinary diversity and ability to rapidly mutate are also huge obstacles in getting a grip on the virus.
Just recently, researchers announced that they’d ID’ed a new strain, the first in 19 years. Despite this, there has been huge progress made in the last decade. In 2009, researchers declared that a vaccine trial done in Thailand had protected a significant minority of humans against the disease for the first time ever.
RV144 is a combination of two genetically engineered vaccines, neither of which had worked before in humans. “Researchers observed a modest level of efficacy over three and a half years — about 30%. So, researchers have initiated a clinical trial in South Africa that is marching along the path to try to confirm these findings from the Thai trial and extend those findings through a number of approaches. ”
As the world’s largest publicly-funded international collaboration focused on the development of vaccines to prevent HIV and AIDS, HVTN has conducted all phases of clinical trials that have involved thousands of people. In addition to two massive trials to test whether giving antibodies to patients can protect them from HIV infection, as of this year, the group has also fully enrolled two similarly ambitious vaccines trials. Called HVTN 702 and 705, these regimes were designed to test whether patients given a vaccine can create antibodies on their own.
Both vary slightly in their approach — 702 is based on the Thai trial, while 705 is focusing on overcoming the viruses’ genetic diversity. What’s very exciting is that the immune responses elicited by these three different vaccine strategies is different within each clinical trial, but there’s similarities across them. And researchers are looking for specific immune responses that we will correlate with vaccine efficacy, with just a few dozen people that will eventually lead us to a more globally effective vaccine that could be used across different populations and routes of exposure.
With hopes high, and even higher stakes, the mood of the vaccine research seems to be one of cautious optimism. But results of both the 705 and 702 vaccine regimes won’t be in until late 2021 and 2022 when the trails are expected to close.
They will certainly be a success and that will get a clear answer as to whether or not these vaccines worked, but I think we also have to be measured in our expectations. And that this is one of the most formidable biomedical challenges we have ever undertaken as a society, as a global research community.