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An easy-to-read explanation of using antibodies for PrEP

, by Emily Newman

Antibodies are an important part of our body’s natural defense against illness and disease. They help our immune system fight off and clear viruses and bacteria that cause infections like the flu, the common cold, chickenpox and more. Now, HIV researchers are testing whether HIV antibodies can be directly given to people who are HIV-negative as a form of pre-exposure prophylaxis (PrEP) or HIV prevention.

Although the research on antibodies for HIV prevention, treatment and cure can be confusing, it’s an exciting area of inquiry. Here, you’ll find an easy-to-read primer about HIV prevention with antibodies, and what you can be on the look-out for if new HIV prevention options (hopefully) start moving from the laboratory into the real world.

Let’s start at the beginning. 

VRC01 antibodyThis is an antibody.

(It’s called VRC01, but we’ll get into that later.)

Antibodies are Y-shaped proteins made by our immune system that help us fight off infections. They do this by “recognizing” and attaching to different foreign things (like bacteria and viruses) and signaling to other cells in our immune system to come and destroy the virus or bacteria.

Vaccines prevent infections by helping your body produce the right antibodies.

Many people receive vaccines to prevent them from getting different diseases. In the U.S., people oftentimes receive vaccines for diseases like measles, mumps, polio and now chickenpox.

Vaccines “teach” people’s immune systems to clear and eliminate viruses with the correct antibodies. How do they do this? Many vaccines are made up of inactive or weakened forms of the virus the vaccine is used to help prevent. When people are exposed to the weakened virus, their immune system “learns” how to respond to the virus with antibodies that help kill the virus. Special immune cells (called “memory cells”) then “remember” how to respond to the virus.

In the future, if the person is exposed to that virus again, their immune system will know how to fight off the infection.

Unfortunately, researchers haven’t been able to make an effective vaccine for HIV.  

There are a few reasons why this is. Importantly, we’re missing what researchers call a “natural model of immunity” for HIV.

vaccine vialsMany people who get the flu recover on their own from the flu. Their immune systems are eventually able to create the right antibodies that fight off the infection and cure the person from the virus. Scientists who develop flu vaccines are able to work backwards to develop flu vaccines knowing what antibody response people will need to produce to fight off the infection.

But as you know, HIV is different. HIV mutates (changes) very quickly which makes it even more difficult to develop a vaccine. And, people’s bodies aren’t able to naturally produce antibodies that fight off and cure an HIV infection. This makes the job more difficult for HIV vaccine researchers, who don’t know exactly how an effective vaccine for HIV could work.

Interestingly, some people living with HIV do produce antibodies that work well against many different strains (types) of HIV. They aren’t perfect—they don’t cure people living with HIV—but they do stop many different strains of HIV from infecting other cells (i.e., they “neutralize” HIV). These are called broadly neutralizing antibodies.

Researchers are now trying to use broadly neutralizing antibodies to develop an HIV vaccine.  

Here are the names of a few broadly neutralizing antibodies that you might have heard of or read about: VRC01, VRC01-LS, 3BNC117 and 10-074.

VRC01 and 3BNC117, for example, stop more than 80% of HIV strains (or variations) from infecting human cells. 10-1074 neutralizes between 60% and 70% of HIV strains.

Broadly neutralizing antibodies were discovered by researchers in the blood of people living with HIV who are elite controllers. Elite controllers are people whose immune systems are able to keep HIV from making copies of itself without antiretroviral medications. (Elite controllers are not cured of HIV, and some opt to take HIV medications to help reduce HIV-associated inflammation and risk of viral rebound.)

The VRC01 antibody, for example, was discovered in the blood of an elite controller in 2010, and has since been reproduced in labs to use in HIV research studies.

Here’s the evidence that these antibodies block HIV infection.

We don’t have solid, definitive evidence that these antibodies prevent HIV in people yet. But, we do have some early data showing that these antibodies are able to block SHIV infection in monkeys. (SHIV is a virus that is similar to HIV that infects monkeys.)

In a study published in Nature in 2016, Gautam and colleagues found that a one-time antibody injection with either VRC01, VRC01-LS, 3BNC117 or 10-1074 prevented monkeys from being infected with SHIV. The monkeys in the study were given the antibody injection and then repeatedly exposed to SHIV once a week for many months (until they became SHIV-positive).

The protection didn’t last forever, but it was sustained.

Monkeys that did not receive an antibody injection became infected with SHIV after about three weeks.

Monkeys treated with VRC01 were protected for about eight weeks; with 10-1074 for 12.5 weeks; with 3BNC117 for 13 weeks; and with VRC01-LS for 14.5 weeks.

Can antibodies prevent HIV infection in people?

That’s the next question researchers want to answer. The only way to know for sure is to do a large, randomized controlled study to compare an antibody therapy to placebo in people who are HIV-negative.

This is precisely what the AMP Studies, which are now underway, aim to do.

The first AMP Study (HVTN 704/HPTN 085) is enrolling 2,700 men who have sex with men and trans people who have sex with men in the U.S. and other sites in South America. The second AMP Study (HVTN 703/HPTN 081) is enrolling 1,500 young women in sub-Saharan Africa.

People in the studies receive an intravenous infusions of VRC01 (one of two doses) or placebo once every eight weeks for about a year and a half. Everyone in the study will be HIV-negative, but at high risk for HIV infection. At the end of the study, the researchers will look to see if less people became infected with HIV who received the antibody therapy compared to placebo.

People in the study will receive HIV testing once per month during the study, and standard of care counseling on reducing HIV risk in addition to condoms and lube.

What’s potentially good about using antibodies for PrEP?

Right now, people in the U.S. have one option for PrEP: the brand-name HIV drug Truvada (which is made up of two generic drugs named tenofovir disoproxil fumarate and emtricitabine). In order for it to work best to prevent HIV infection, people need to take it every day. People who miss doses are less likely to be protected from HIV infection if they’re exposed to HIV.

Antibody-based PrEP may improve on this option by giving people an option for longer-lasting protection. The AMP Study is testing an antibody concentration that may last for up to two months. Instead of taking a pill every day, people receive an antibody treatment once every two months.

Another possible benefit to antibodies is that they are generally safe and well-tolerated.

What might a future antibody-based PrEP look like?

Researchers are continuing to search for, and develop, antibodies that are even more potent (stronger) and protect against even more strains of HIV. Researchers are also beginning to test combinations of antibodies, to see if that offers fuller protection against HIV.

Future research on antibody-based PrEP is likely to test how long people can be protected after one treatment. The AMP Study provides doses of antibodies every two months, but future therapies may only require treatments every three or six months if more potent antibodies are used.

Different dosing methods may also be tested. The AMP Study delivers antibodies through an infusion, but delivering antibodies through a shot under the skin would be faster and easier.

Interested in joining an HIV vaccine research study? Find out how. Read more on BETA about how HIV vaccines may be used to prevent and cure HIV with this conversation with Dr. Aliza Norwood.

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