MANILA — The COVID-19 health crisis has captured much of the world’s attention and resources. At this week’s 23rd International AIDS Conference, the pandemic has also highlighted gaps in investments and engagement in HIV vaccine development efforts.
What can be done to mitigate the financial impact of COVID-19 on country resources and maintain sufficient funding for programs, such as those targeting HIV/AIDS?
In the span of just five months, the U.S. Biomedical Advanced Research and Development Authority has invested close to $4 billion in six companies working on COVID-19 vaccine research and development, according to its website. In contrast, total estimated funding for HIV vaccine R&D in 2018 from both public and private sources was just over $840 million.
In a presentation at this week’s conference, Dr. Jerome Kim, director general of the International Vaccine Institute in South Korea, highlighted the stark difference between some of the largest companies actively involved in COVID-19 vaccine R&D today versus those working on an HIV vaccine. Only one, Johnson & Johnson, is actively involved in HIV vaccine R&D at present, he said.
The reason for this is twofold, Kim continued. First, companies are able to leverage risks shared by governments in COVID-19 vaccine development. Second, companies know there is a huge demand for that vaccine in high-income markets as well.
“Where's the market for HIV vaccines? The largest need for HIV vaccines is in the developing world. And those vaccines are not going to be sold for the same price that a company would get in the United States or Europe,” Kim told Devex in an interview.
“The incentives for companies to participate in vaccines that have a high-income and low-income market are very different from those that only have a low-income market,” he added.
But science also poses challenges to the development of an HIV vaccine, he said.
Devex spoke to Kim to talk about the challenges in HIV vaccine development today and how current efforts to find a COVID-19 vaccine could also accelerate progress toward a vaccine for the 40-year-old epidemic.
This conversation has been edited for length and clarity.
In your presentation, you mention that a lot of things that have happened to COVID-19 vaccine development efforts have not happened to HIV. How does the HIV community of researchers and scientists feel about that?
The diseases are so different. It would be great if somehow the vaccines for HIV were to be incentivized in the same way that the vaccines for COVID-19 are. I mean, having these big companies with lots of experience developing vaccines, it makes it so much easier.
And you see it. I mean, you see a huge amount of innovation in COVID-19. We don't see that same focus with HIV, which is a real shame. On the other hand, we have hundreds of millions of dollars going to HIV vaccine research. So again, it is funding a significant amount of work, and it's taught us a huge amount about viruses, about the immune response, about how we can develop vaccines that target certain things. We've learned a lot, and we can use those tools.
“There's still a tremendous amount to be done in HIV vaccines, and I wish that the big companies would get engaged again.”— Dr. Jerome Kim, director general, International Vaccine Institute
HIV is a different kind of pandemic threat. But we have highly active antiretroviral therapy. We have PrEP [preexposure prophylaxis], and now we have long-acting PrEP that may be good for up to a year. So, gradually, the science is driving HIV.
And I think that's actually a big contrast. I mean, I tried to make that clear in the presentation. With HIV, science has been so central to all the advances that we've made. We don't have that same dependence on science in the response around COVID. I mean, scientists, yes, but in terms of the societal response, we don't have the same support for the benefits that science can bring to this question.
You made that really striking comparison between large companies’ involvement in HIV and SARS-CoV-2 vaccine development. How did that happen, and how much is COVID-19 helping or delaying HIV vaccine development?
When you look at the major companies involved in COVID-19 vaccine development — Pfizer, Merck, GlaxoSmithKline, Johnson & Johnson, Takeda, and AstraZeneca, which actually doesn’t really make vaccines [but is] really, really involved, putting all of its resources into accelerating vaccine development — these are big companies.
They know how to make vaccines and drugs. They know how to do things efficiently. And they've just been given funding, actually — now the numbers are about $4 billion by the U.S. government — to really accelerate vaccine research and development. What they're doing is they're using that funding to help leverage risk.
They also, I think, recognize that this fits into a model that we're very familiar with: Diseases that have a high-income country market, and COVID-19 certainly, has affected the United States, Canada, Australia, Europe. Those vaccines will be like the vaccines that the companies make for pneumonia or human papillomavirus or influenza.
On the other side, COVID-19 is also a problem of developing countries. Here, companies will have to adjust the price. And already, organizations like the Global Alliance for Vaccines and Immunisation [Gavi, the Vaccine Alliance], the Coalition for Epidemic Preparedness Innovations, and the World Health Organization are trying to put together a framework that will allow low- and middle-income countries to be able to access these vaccines at affordable prices. So again, we're really working on this dual market system.
Now contrast that with HIV: one major company — Johnson & Johnson. A number of companies have pulled out — Merck, GSK / Novartis, and Sanofi. Why? Where's the market for HIV vaccines? The largest need for HIV vaccines is in the developing world. And those vaccines are not going to be sold for the same price that a company would get in the United States or Europe.
So you can see that the incentives for companies to participate in vaccines that have a high-income and low-income market are very different from those that only have a low-income market or a developing country market.
The U.S. government has underwritten a significant amount of HIV vaccine research to help to advance what we know and what we can do about prevention of a virus that really is a problem in the United States, but the burden of disease and new infections in the United States is much smaller than the burden in the developing world — in sub-Saharan Africa, in particular.
There's still a tremendous amount to be done in HIV vaccines, and I wish that the big companies would get engaged again.
How can we get the same enthusiasm we're having with COVID today to the development of an HIV vaccine?
I think that one of the things is when the companies look at COVID-19, they see a kind of disease that they've been successful at before: A human gets infected with COVID-19 — by and large, that human being will mount a tremendous immune response, a protective response, and that same immune response, we hope, we think, protects that person against future infections for some period of time.
So if you look at measles or polio or hepatitis A, the body does exactly the same thing. It sees the virus, it attacks it, gets rid of it, and protects the body against future infection.
The immune system with HIV is always one step behind. It never really completely eliminates the virus. And that means that the target itself will be hard, because we can't just copy the human immune system when we design the vaccine, which is what we're doing with COVID-19.
I think with HIV we're still arguing: What's the most important thing? Is it cytotoxic T cells? Is it T helper cells? We think it's broadly neutralizing antibody, if we can generate it.
So we're still searching and we don't know how to induce those responses. Whereas for COVID, there've been a number of successful trials protecting monkeys against COVID-19. We don't have a monkey model that uses HIV as the challenge. So, some differences there.
Now, a company looks on that confusion and says: “Do we really want to put a billion dollars on a pathogen where the market will be primarily in sub-Saharan Africa and where we don't really understand if the vaccines that we have now, the kinds of vaccines that we make, will actually protect?”
That's a huge risk. Whereas for COVID, they see the light at the end of the tunnel, in a sense. It fits into a model where they've been successful before. And the U.S. government and other governments are significantly de-risking their development costs.
Would you say the biggest barrier toward an HIV vaccine is on science or on the investments?
The European Union, the United States, the [Bill & Melinda] Gates Foundation have all been very generous with regard to investing in the science around HIV immune responses and the ability of vaccines to induce the protective immune response. It's a lot about science. I mean, if the science were on firmer ground, I think the companies would be more willing potentially to undertake that challenge.
Again, with COVID-19, although there's a lot that we don't know because we’ve only known about this virus for six months, there's a lot that we assume is correct about COVID-19 that seems to be born out of what we understand about infection and what we understand about animal models.
What could potentially change in HIV vaccine development post-COVID?
So there are some potential silver linings, although right now it looks like the HIV vaccine world is carrying part of the COVID vaccine effort — which is important and reasonable, given the threat that COVID poses to countries around the world.
I think the first would be in proof of concept around platforms. Everyone talks about how quickly Moderna and INOVIO got their platforms out and got tested in humans. But everyone points out there is no RNA vaccine currently licensed; there is no DNA vaccine currently licensed; there's no chimpanzee adenovirus vaccine currently licensed.
Hopefully … several will be shown to be safe and effective and then approved by the U.S. Food and Drug Administration or the European Medicines Agency that gives credence to the platform. And maybe then it'll be easier to develop vaccines using similar platforms for HIV.
[Janssen’s Zabdeno, an adenovirus serotype 26-based vaccine against Ebola, received marketing authorization from the European Commission on July 1. The same platform is being tested in vaccines against other viruses, including HIV. ]
The other possibility is maybe someone will come up with a better adjuvant.
For instance, Oxford’s chimp adenovirus candidate. So, say it's shown to be safe and effective — how long will that protection last? If we look at natural infection with coronaviruses, often the level of neutralizing antibody isn't very high, and it tends to be transient. Now, are those people protected? We actually don't know. But we're worried that the duration of protection will be short.
As we develop the second generation of COVID-19 vaccines, maybe we'll begin to introduce new adjuvants that will strengthen and give you a higher level of antibody that's produced and will allow that immune response to last for a longer period of time. And that would be important. And maybe COVID vaccines can help accelerate that.
Update, July 14, 2020: This article has been updated to clarify that Janssen’s Zabdeno, an Ad26-based vaccine, has received marketing authorization from the European Commission.