Dr. Robert Gallo, MD, talks with Eureka about why we should consider the polio vaccine as a stopgap in the pandemic
Virologist Robert Gallo, MD, has had a long and storied career in academic and government research. He is the Homer & Martha Gudelsky Distinguished Professor in Medicine, co-founder and director of the Institute Human Virology (IHV) at the University of Maryland School of Medicine and co-founder and international scientific adviser of the Global Virus Network.
He spent three decades at the US National Institutes of Health. Most of the world knows him as the co-discoverer of HIV—a distinction he shares with a team from the Pasteur Institute that had also isolated the retrovirus. He also identified how chemokines, natural weapons in the immune system’s defenses, can be potent foes of HIV. These findings led a new class of antiviral drugs to treat AIDS.
Since 1996 he has been part of IHV, which Gallo co-founded with Robert Redfield, now director of the US Centers for Disease Control and Prevention.
Despite his deep roots in HIV, Dr. Gallo’s current focus is, not surprisingly, COVID-19, which emerged in China last year and within four months morphed into a full-blown pandemic. As usual, Dr. Gallo’s research strategy has raised eyebrows. Unlike the antibody and RNA vaccines that are all the rage in COVID-19 science, Gallo is putting his energies behind repurposing the oral polio virus vaccine developed in the 1950s by Albert Sabin. He believes this approach could be a stopgap before we obtain, if ever, an effective, proven safe, durable vaccine that is ready for distribution and that stimulates the adaptive immune system. He thinks this could have and should have been Plan A while other vaccines are under development..
The polio vaccine was instrumental in bringing an end to polio in most countries—but is it a reasonable choice against a completely different virus that primarily affects the respiratory system? Dr. Gallo thinks so and he is hoping to convince the US National Institutes of Health to fund a large-scale clinical trial to test the polio vaccine’s efficacy against SARS-CoV-2. He and his colleagues co-authored a perspective piece in Science this year, suggesting that live attenuated vaccines, like the oral polio vaccine, can also produce broader protection against unrelated pathogens, possibly by inducing interferon and other innate immunity mechanisms not yet identified. Innate immune responses are the first to respond to an infection, but until recently were not thought to have any immunological memory of the pathogens they come in contact with.
Eureka recently spoke with Dr. Gallo about his work on a COVID-19 vaccine, how the SARS-CoV-2 virus is mutating, and how well the public health community has been doing fighting this pandemic. Here are his edited responses.
Eureka: Why do you think the oral polio vaccine is a good strategy against SARS-CoV-2?
Dr. Gallo: Let us start with Maurice Hilleman, who is arguably the most successful vaccinologist in history. Hilleman used to say that when you are making a vaccine, start with feasibility, ease of distribution and availability and safety. We have 70 years of experience with oral polio vaccine, and it has a tremendously safe record. Complications from oral polio have been zero in a vaccinated population, as the bulk of the world today is. We can easily produce it and there is plenty of evidence of surviving the cold chain. And large-scale clinical studies of oral polio vaccine against nonspecific prevention of disease, including in Russia, found that it was effective against influenza virus and genital herpes simplex virus.
Eureka: What evidence is there that innate immunity could control SARS-CoV-2?
Dr. Gallo: Innate immunity is a hot area of immunology, but no one understands it very well. Interferons—so-called because they interfere with viral replication—and cytokine molecules are big parts of the innate immune response, but there are other things involved as well, such as those derived from myeloid lineage. It is thought, secondhand, that the bats that harbor coronaviruses are able to keep these viruses in check using nothing more than innate immunity. We also know that other vaccines can induce innate immunity against unrelated viruses. The BCG vaccine [a live attenuated vaccine against tuberculosis], has been shown to stimulate innate immune responses for a prolonged period of time, what we refer to as trained immunity. Both the poliovirus and coronavirus are positive-strand RNA viruses, which means it is likely that they will induce and be affected by common innate immunity mechanisms. More than one serotype can be used sequentially to prolong protection, and the vaccine is cheap and easy to administer. Over 1 billion doses of oral polio virus vaccine are produced and used annually in more than 140 countries. So if you ask am I certain this will have efficacy, I’d say, I am certain of nothing. But if I’m betting I would give you at least a 5:1 odds it would work.
Eureka: How receptive have regulators and funders been to this idea?
Dr. Gallo: Dr. Redfield is very excited about this. I talked to Tony Fauci [Director of the US National Institute of Allergy and Infectious Diseases] and was enthusiastic or so it seemed. We are really waiting for NIH support on this. We have discussed it with FDA and they were positive too. An IND will put forward to the FDA when funding becomes available. One issue that comes up is durability. Innate immunity is measured in a weeks or hours, not months or years. However we can boost again and again for roughly a half year or a full year. That can at least get us through this pandemic.
Eureka: What about vaccines that induce neutralizing antibodies?
Dr. Gallo: We always look for vaccines that induce neutralizing antibodies. The first paper ever to come about HIV and neutralizing antibodies was co-authored by me and Marjorie Robert-Guroff. But we never found a vaccine that correlated with the presence of neutralizing antibodies. And this isn’t just the case for HIV. Yet today, 90% of 160 vaccines against SARS-CoV-2 are made off the spike protein. Neutralizing antibodies are still thought to be the clearest way to a vaccine. I’m saying we need a Plan B if they don’t work.
Eureka: There has been recent research showing that coronaviruses carrying a certain mutation infect more cells and are more resilient than those without it. Do you think it is plausible that these biological changes in the virus might be one reason it spread so rapidly in some countries.
Dr. Gallo: Of course it is possible but we don’t have proof yet. My colleague and I published a paper a few months ago that described unique mutations in the RNA polymerase gene—which the virus uses copy RNA—in patients in Europe and North America. The mutation is now surviving and it is virtually like a new strain of the virus. Unfortunately, we can’t get samples from the asymptomatic or pre-symptomatic individuals, of which we know virtually nothing.
Eureka: Lastly, how well do you think the public health community is doing in fighting this virus?
Dr. Gallo: If I were in the shoes of the public health leaders I am sure I would be making mistakes, too. It is hard to say we have distinguished ourselves as a nation or as a world. This is why we created the Global Virus Network in 2011. We wanted to make sure there were adequate numbers of young people coming into the field of virology and to make sure there was expertise spread throughout the world. We have been able to achieve that. We feel something like the GVN should have been in a much more public position. The World Health Organization doesn’t have much money, when something emerges that is new or different who do they call? They have to call people like us.