Countdown to Zero: The path to an HIV vaccine

Scientists at Fred Hutchinson Cancer Research Center who are working on preventing, treating and potentially curing HIV/AIDS were among those interviewed for “Countdown to Zero,” a VICE special report on the progress being made to end the HIV pandemic. The program premiered on HBO Tuesday — World AIDS Day — and for the next few weeks is available for streaming. We talked with one of the experts featured, internationally renowned virologist and Fred Hutch president and director emeritus Dr. Larry Corey, who is founder and director of the HIV Vaccine Trials Network (HVTN), the world’s largest international collaboration working to develop preventive HIV vaccines.

You talked with VICE reporters about an endgame for HIV. What do you mean when you say endgame?

To me, the endgame is when we reduce the number of HIV incidence cases in the United States to less than 50, or less than 100. The only way that’s been done throughout the history of infectious diseases is with a vaccine. That has to be a 95 percent effective vaccine, like vaccines against polio or rubella or mumps.

Why do we still need a vaccine when we now have antiretroviral therapies that can stop HIV from progressing to AIDS?

Using antiretroviral drugs and putting everybody into therapy is important. But that is an approach that will never get to my endgame. With asymptomatic acquisition and asymptomatic transmission, you’re never going to get to less than 100 cases. For the last decade, the U.S. has recorded about 50,000 new cases of HIV yearly. With our current strategy to test and treat all people as soon as possible, we may reduce the transmission rate to 25,000. That would be a beautiful thing. But you’re not going to get to less than 100 cases yearly.

“Test and treat” is necessary, but it’s also costly. For many countries with a high burden of HIV, these approaches create a true Sophie’s choice. We would rob Peter to pay Paul, especially for some countries that also have issues with diabetes and obesity and child health and all this other stuff. How sustainable over time is that approach? When you look at the ultimate endgame from an economic point of view and a humanitarian point of view and a public health point of view and individual care point of view, it’s going to be incredibly important and cost-effective to make a vaccine.

Scientists have been working on an AIDS vaccine for more than 30 years now. Why is it so challenging?

We’ve been unable to develop approaches that overcome the virus’s plasticity for avoiding immune responses. It’s quite different from any other virus, even from influenza [which also mutates rapidly]. Sure, [influenza has] antigenic variation, but that antigenic variation is reasonably constant so that the body’s antibodies can partially block the virus. With HIV, the antibodies you make and a lot of the immune responses you make do not block the [mutated] virus that’s just down the street at the same time. A flu vaccine blocks the virus down the street.

So far the only vaccine to show any protection against HIV was the so-called Thai vaccine, which in 2009 showed 31 percent protection in vaccinated trial participants compared to placebo-treated participants. What progress has been made since then?

We’re starting to identify classes of antibodies that will block multiple strains of HIV, maybe lots of strains, maybe 40 or 50 percent of strains or up to 80 or 85 percent of strains.

We have two paths [toward a vaccine]: one of them is non-neutralizing antibodies [as in the Thai vaccine]. The other path is to develop these [broadly] neutralizing antibodies. In the end, I think we’ll combine those two paths, and that will get us to the promised land of a vaccine that is 80 or 90 percent effective.

The HVTN started an early-phase clinical trial in South Africa in February on a modified version of the Thai vaccine intended to boost effectiveness and duration. When will you know whether that is working well enough to expand into a larger trial?

We’re looking at the middle of February.

And if you expand to a larger trial, how long will it take to know if the vaccine will work well enough to be licensed?

Three and a half to four years.

It’s been said that achieving 50 percent protection would be good enough to license. What do you hope to achieve?

Once you get to the 50-60 percent range, then you learn so much with respect to what we call the correlates of protection, the levels of antibodies you need to have. Then also [working on the second path] we may also get a neutralizing antibody that looks like it’s 30, 40 or 50 percent. If you put the neutralizing with the non-neutralizing, you get 90. That’s what I mean by these two paths may merge.

Tell me more about the second path, the one toward broadly neutralizing antibodies, that you’ll be starting next year.

It’s not that often that you know that you’re starting a landmark study. It’s not very often you even use the word landmark. But you sort of know that this one is a landmark study. We will for the first time be infusing [using an IV] broadly neutralizing antibodies that technology has now allowed us to make. If it establishes that neutralizing antibodies are potent and will work to prevent acquisition, a whole set of scientific dominoes will fall from that. It would tell us what concentration of antibody will work that is the most effective and efficient. It would help us with setting up [preclinical] models so that they’ll be more predictive. We’re able to do this glorious test of concept study that we know will define a lot of things for the future.

Just so people understand, you’re not going into the broadly neutralizing antibodies trial with the expectation that a vaccine would come out at the end, correct? You’ll be using an IV to directly deliver the broadly neutralizing antibodies, to see what they do in the body, see if they give the responses you anticipate, and how much you need, and then you sort of work backwards to develop a vaccine that elicits them.

We would work backwards to make a vaccine. Or if turns out that our current technologies won’t allow us to elicit these responses, then we have to figure out how to give these antibodies directly, without a vaccine. It would be more complicated and more difficult than a simple vaccine. But if that’s the technology we have to move forward, then that’s the technology we have to move forward.

Where did the broadly neutralizing antibody you’re testing come from?

The antibody we’re testing is derived from B cells [a type of immune cell] from a patient in the United States. The B cells were isolated and tested at the National Institutes of Health Vaccine Research Center in Bethesda, Maryland, by Dr. John Mascola’s team. They then manufactured the antibodies in their biotechnology facility. Antibodies that are broadly neutralizing are seen in about 15 to 20 percent of people with HIV.

But the antibodies develop too late to prevent infection, which is the point of inducing them or infusing them before infection, right?

Yes.

Has the public gotten complacent about HIV?

Sure there’s AIDS fatigue. That’s why professionals and leaders need to solve problems and do it with persistence, until they’re solved.

Fifty thousand people per year continue to get HIV in this country. That is not trivial. A lot of them are black or brown or in rural areas of the United States. Occasionally you’ll see a blip of interest when there’s an HIV epidemic associated with IV methamphetamine use in the middle of Indiana. Or we have Charlie Sheen. Real people get HIV. And worldwide, there are 2 million new infections a year. That’s 2 million real people.

[Yet] look at what’s going on in Congress. They’re talking about cutting back on the HIV budget. And they’re framing it as relating to the economic costs that are going into healthcare throughout the world, into which we put considerable money. The dollars that go into this will come back to the United States in enormous dividends for our children – for my grandchildren – as well as for us globally and economically. Health as a form of foreign policy is actually quite important.

What do you hope people take away from the HBO documentary, “Countdown to Zero”?

To me, the hope is for the public to be aware that HIV has not gone away and that scientific advances are being made. We have the tools and the means and we have established the scientific persistence to prevent real people from getting infected and to really develop an AIDS-free generation for our kids. We should do that. We have the capability of doing that. That’s what our magnanimous society should be doing.

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