Robert Gallo and Luc Montagnier reflect on the discovery of HIV and the future of vaccine research with IAVI Report staff
Robert Gallo, 74, is the director and co-founder of the Institute of Human Virology (IHV) at the University of Maryland and co-founder of Profectus BioSciences. Thirty years ago, he was working as a virologist at the US National Cancer Institute when the first cases of AIDS were reported. In 1984, a year after French researchers identified a new retrovirus that they called lymphadenopathy-associated virus (LAV), Gallo’s team also reported the isolation of a new retrovirus, but called it human T-lymphotropic virus (HTLV) type III. Both were later determined to be strains of HIV, the cause of AIDS. Recently, IHV was the recipient of a US$23.4 million grant from a consortium led by the Bill & Melinda Gates Foundation to fund preclinical development of an AIDS vaccine candidate that Gallo and his IHV colleagues developed.
Q: You’ve now lived through three decades of AIDS. What were those early days like?
Gallo: It was horrible, stressful, and I’ll add a third adjective, scary. That time was unimaginable. You saw patients who you became friendly with and watched them die. There was nothing we could do for them. Then there were the crackpots saying that AIDS doesn’t exist, or that we created it to kill people.
When we solved the cause of the disease, I couldn’t understand the attitude of the activists because without knowing the cause of AIDS, we couldn’t move forward. But they were worried about discrimination, prejudice, and stigma. They thought we tattooed them without giving them any help.
Q: How would you describe your role in the discovery of HIV?
Gallo: Between 1982 and 1985 there was a tremendous amount of papers published, done chiefly by my lab. We provided the idea in 1982 that a retrovirus might be the cause of AIDS, and our lab succeeded in growing T cells, obtained from a man with AIDS, that contained two viral forms. But there is no question that Luc Montagnier’s group at the Pasteur Institute made the first report of HIV being isolated from a patient. There was never a controversy over who discovered the virus. The dispute arose later when we developed a blood test for HIV and the Pasteur Institute wanted a share of the royalties. Importantly, our report on an extensive number of HIV isolates, plus the blood test, was the evidence that HIV was the cause of AIDS. For these reasons, Luc and I agree on co-discovery.
Q: Are you more hopeful now about HIV vaccine development than you were in 2008 when you compared the results of the STEP trial—which showed that Merck’s vaccine candidate was not effective—to the Challenger space shuttle disaster?
Gallo: I wasn’t pessimistic when I made that comment. I’m one of the most optimistic people in the field of AIDS vaccine science. I said that because I thought the STEP trial was a mistake from day one. It should not have gone forward. From my viewpoint, this was not the kind of vaccine to go forward with. The NIH [National Institutes of Health] and Merck made it sound good on paper, but to me it just didn’t make sense. I don’t think we should test a vaccine based solely on cell-mediated immunity. I’m not saying cellular immunity is unimportant and antibodies are the masters, but you better have some antibody-mediated protection.
Q: You’re now actively engaged in AIDS vaccine research (see Vaccine Briefs, this issue). What do you think it will take to make a preventive AIDS vaccine?
Gallo: I believe antibodies must be part of an effective preventive vaccine. I believe broadly neutralizing antibodies are important. However, I don’t think they are the only thing that is important. Neutralizing antibodies are just one way to skin a cat. I think non-neutralizing antibodies will likely have a role too. And I believe that a successful vaccine must come close to providing sterilizing immunity. This point seems to have been forgotten.
Q: What do you make of the results of the RV144 trial in Thailand, the first to show any efficacy?
Gallo: Since RV144 was the first trial to show efficacy I would analyze it up and down. I don’t believe the critics that said it didn’t work and attacked the US Army [a collaborator in the trial] unfairly.
Q: So do you think the field is on the right track?
Gallo: I think so, but we need to follow the science. I am aghast at arguments that claim that monkeys don’t predict how vaccine candidates will work in humans and that we should just go forward anyway with clinical trials. We need to be extremely cautious against using that philosophy. Monkeys aren’t perfect but they are a good model. The alternative is that he or she who has the power simply and arbitrarily decides what vaccine goes forward.
Luc Montagnier, 78, is co-founder and current president of the UNESCO World Foundation for AIDS Research and Prevention in Paris. Last year, Montagnier accepted a professorship at Shanghai Jiao Tong University. In 1983, he and his colleague Françoise Barré-Sinoussi were the first to report the isolation of a new retrovirus, later determined to be HIV, from a patient, a finding for which they received the 2008 Nobel Prize in Physiology or Medicine.
Q: What are your earliest memories of the discovery of HIV?
Montagnier: I remember reading in the newspapers that there was a new disease, the gay disease. When we learned of the transmission by blood in transfused patients and hemophiliacs, the idea started that it could be caused by an infectious agent—a virus or a bacterium—and since it was transmitted also in filtered products for hemophiliacs it was more likely to be a virus. There was also concern that the AIDS agent could be transmitted in the hepatitis B vaccine, which was made at the time at the Pasteur Institute. So we were asked to see if there could be some kind of infectious agent. Since we had the technology to detect retroviruses and grow human T cells, we started to look for a retrovirus.
I used a lymph node biopsy of a gay man who had swollen lymph nodes and I cultured his T cells. Three weeks later my associate, Françoise Barré-Sinoussi, was able to detect some retrovirus reverse transcriptase activity in the culture supernatant. So, I set up a group of about ten people, and this group within months in 1983 could show that the virus was new and was the best candidate to be the cause of AIDS.
Q: What did you think when you first saw this result?
Montagnier: We had the virus but we didn’t know whether it was just a passenger virus or the cause of AIDS. So at this time we were moderately excited. But we still had to look for a correlation with the disease. This was done during 1983 and 1984, when my colleagues showed that there were antibodies against this virus in many pre-AIDS patients, and in some AIDS patients as well. We could also isolate the same type of virus not only from gay men, but also from hemophiliacs and from African patients, indicating that this virus was probably the best candidate for being the cause of AIDS.
Q: What was the response to your first paper in 1983?
Montagnier: Well, it was mostly ignored. Some virologists, like Robert Gallo, thought it could be a variant of human T-leukemia virus (HTLV). We had some difficulty publishing further papers because we stated that it was quite a different virus from HTLV. We called the virus LAV (lymphadenopathy-associated virus) because it was isolated not from a full-blown AIDS patient, but from a pre-AIDS patient. Then, after the publication, we found the same type of virus in the blood of full-blown AIDS patients. I think the first time I could convince at least some of my colleagues in the US was at Cold Spring Harbor in September 1983, where I presented all the data indicating that this was the right virus to be the cause of AIDS.
Q: Do you think it will be possible to develop a preventive HIV vaccine?
Montagnier: That’s a sensitive question. I think it’s important to first continue some basic research in order to detect all forms of the virus that are transmitted. My approach is to first try therapeutic vaccines, which could be more easily tested in clinical trials in a very short period of time. Clinical trials of preventive vaccines are expensive and questionable in terms of the results because you need to deal with a large population in order to obtain significant results. If a therapeutic vaccine works, then we can extrapolate it to a preventive vaccine.
Q: Regarding the Nobel Prize, when you got that call were you surprised?
Montagnier: I cannot say I was very surprised because every year some journalists called me in advance of the announcement to see if maybe this is the year for me to win the Nobel. I was in Africa at that time, in a meeting in Ivory Coast, and of course it was symbolic as AIDS is mostly in Africa and a disease of developing countries.
Q: What would you tell people who are entering the field? What is there to still learn about HIV, 30 years later?
Montagnier: There are still many things to find. It’s not finished. Even though we know very well the molecular biology of this virus, we still know little about how it is transmitted, why antiretroviral treatment cannot get rid of it completely, and so on. There are still basic questions to answer, and at the same time we have to save the lives of patients and try to reduce the duration of treatment. I think this is key if we are to beat this disease in the 21st century. I hope I will see that during my life.