The start of this year’s HIV Research for Prevention Conference brings with it new findings that show the potential of special antibodies to prevent HIV infection. We unpack the study and break down the key concepts.
There’s a new player in the HIV prevention field. Newly released results from the 4th HIV Research for Prevention Conference offers fresh insight into how the immune system can prevent HIV infection — and serve as a guide for a potential, long-awaited HIV vaccine.
The pivotal research, which is the first of its kind to announce results, builds on ideas from vaccination and tests a new idea: whether special antibodies — the type that can help someone fight off multiple forms of the virus — can be used to prevent HIV infection.
“These were complex and well-designed trials of a novel HIV prevention concept, and the results move the field forward in important ways,” says Mitchell Warren, the executive director of the US-based advocacy organisation, Avac.
“The AMP trials show that a broadly neutralising antibody can reduce the risk of acquiring viruses that are very sensitive to that antibody. This is welcome news; it is the first evidence in humans that intravenous infusions of a broadly neutralising HIV antibody can reduce a person’s risk of acquiring HIV via sex.”
A vaccine works by training your body to protect itself from a particular virus. This is done by safely exposing your body to parts of the virus or a tame or dead version of the virus in the hope of getting it to produce antibodies and killer cells, which will then be able to fight off the infection.
Antibody-mediated prevention, or AMP, works in almost the opposite way. Rather than trying to get your body to produce its own antibodies, people are instead directly given antibodies that can protect them from infection.
The AMP findings announced at a Tuesday press briefing for the conference show that this method of using antibodies can protect people from contracting some strains of HIV.
“Like most innovative research studies, AMP produced complex results that also raise important new questions for researchers,” said Roger Tatoud, deputy director of HIV programmes and advocacy at the International Aids Society.
To help you better understand the study, we break down some of the key concepts and what the results mean.
What is a broadly neutralising antibody?
When a person gets sick, their body will automatically try to fight off the infection.
It does this using the immune system, which serves as a natural defence against foreign invaders, such as viruses.
The first line of defence against an attack is proteins called antibodies. The antibodies lock onto the invader which stops the virus from infecting your cells and makes it easier for your body to identify the virus, or other harmful pathogens, that need to be destroyed.
These antibodies are a specific response and are tailored towards a particular invader — in other words, the antibodies for each infectious agent, or pathogen, are different.
But occasionally, your immune system generates a very special type of fighter called a broadly neutralising antibody. This means that rather than being specific to just one particular version of the virus, it can fight off multiple forms of the virus.
Why are broadly neutralising antibodies important for HIV?
HIV is an incredibly tricky virus because it changes rapidly.
When HIV makes copies of itself — as it replicates — some of the new viruses contain genetic changes called mutations. The mutations are errors in the genetic code of the virus that pop up as the virus spreads in your body and the number of changes that happen during this copying process creates a new version of the virus that is different from its original form.
That is why we have two different strains of HIV — HIV-1 and HIV-2 — and it’s complicated to create a vaccine that works for both strains or even for variations, in the form of subtypes or clades, within each strain of the virus.
This wide array of viruses makes it challenging for your immune system to mount a good defence. As the antibody finds its target, the virus begins to change, which makes it very difficult for your body to keep up with producing the right kind of antibodies to fight the virus.
In trying to fight off HIV after you’ve already been exposed, the immune system will never be able to catch up. Broadly neutralising antibodies help to solve this problem.
How? Instead of just fighting off one version of HIV, they are able to help neutralise (i.e. stop it from infecting your cells) multiple forms of the virus.
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What is the AMP study?
To get around the problem of your body not being able to effectively fight off HIV, researchers are trying out a different method of protection.
This is called antibody-mediated prevention, or AMP, where people are given antibodies — designed in labs — that can potentially protect them from getting infected with HIV.
The AMP trials, which are comprised of two efficacy studies being run in parallel, test whether a manufactured antibody, called VRC01, can safeguard people against contracting HIV.
This antibody was developed by the Vaccine Research Centre at the US government’s National Institutes for Health and some lab studies have shown it can block about 80% of the different types of HIV currently circulating. The AMP trials have sought to see how this translated outside of the lab.
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The first trial, named HVTN 703/HPTN 081, enrolled 1 900 women in sub-Saharan Africa — in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. The second study — called HVTN 704/HPTN 085 — included 2 700 men who have sex with men and transgender men and women in Brazil, Peru and the United States.
Overall, a total of 4 600 people were involved in the trials.
Participants in the trials were split into three groups — a third received a high dose of the antibody, a third a lower dose and the remaining third a placebo, where they were given a salt water solution not containing any antibodies.
The antibody was given to people via infusion, or using a drip. This was done at eight-week intervals over 80 weeks, translating to 10 infusions over 20 months.
The idea behind the study was not just to find out if the VRC01 antibody could prevent HIV infection, but also to find out how safe it was to do and how much of it someone needed to receive for it to be effective. Researchers also wanted to gain a better understanding of the immune response needed to protect someone from the virus.
What were the findings?
In a promising finding, the study’s principal investigator, Lawrence Corey, announced that the AMP studies had shown that participants who received the antibody were 75% less likely to become infected with strains of HIV that are sensitive to VRC01.
The downside is that the results also show that the VRC01 antibody was not able to offer protection to a wide variety of HIV strains. Ultimately, the antibody has little impact and did not offer protection against about two-thirds of the HIV currently circulating in the world.
“The point of the study was actually to demonstrate this concept of could we a) develop an antibody and show that it was effective and b) get a laboratory assay that would predict what would be susceptible and not,” explained Corey, who is also the director of the Fred Hutchinson Cancer Research Centre.
Because the study showed that using only one antibody, in this case VRC01, could only offer protection to limited forms of the virus, it indicates the need for future studies to look at a combination of antibodies.
There are several broadly neutralising antibodies that have been found for HIV — and are already being tested — and more research is needed to look at which antibodies are best paired together in order to offer maximum protection to the various strains of HIV.
Part of the study’s findings also helped show that a specific test can be used to help predict the protection that can be offered by a particular antibody. The test can now be used in future work to indicate which antibodies can offer protection and in what combination.
Corey concluded: “The trial, as a test of concept, was wonderfully successful and sets the landmark that we can use broadly neutralising antibodies for the prevention of HIV. That will be a new modality and a new toolbox and it opens up the field.”