Duke’s long leadership in vaccine research and the Duke Human Vaccine Institute’s (DHVI) dogged 25-year pursuit of answers to HIV put the university and health system in an excellent position to address the sudden, global challenge of the novel RNA coronavirus SARS-Cov-2 when it began to sweep around the world in 2020.
Four members of the DHVI faculty joined with Colin Duckett, the vice dean for basic science in the Medical School, to discuss immunology and vaccines as part of Research Week on Feb. 3. Not surprisingly, much of their discussion focused on COVID-19.
On Current Progress Against the Pandemic
David Montefiori, PhD, director of the Laboratory for AIDS Vaccine Research and Development
“Unfortunately, I believe that COVID is going to be with us for a long time. There's been so much seeding of this coronavirus throughout the world that it is going to be very difficult for it to just go away. The hope though, is that at some point in time — and hopefully we're getting there soon — enough people will have experience with this virus where they've either been infected and they have some immunity or they get vaccinated, that we will reach a point … that the virus will be less lethal for people who are at high risk of severe disease and death.”
Kevin Saunders PhD, DHVI director of research
“As long as you have up-to-date immunity against the virus, it's not going to become a serious infection to you, so that it would be something that causes hospitalization. It's going to be around, you're going to come in contact with it at some point, so you need to be protected.”
Georgia Tomaras PhD, director of the Duke Center for AIDS Research
“We have learned that this is going to be unpredictable. It may be like the weather. We need to change our response to the situation. We’ve really got to think of this as, ‘This is with us.’ We need a more overarching strategy and response plan as a community to better deal with this, in terms of community health and response, but also scientific responses.”
Wilton Williams PhD, director of the DHVI Viral Genetics Analysis Core
“We as a society have a role to play to shorten the length of this pandemic. Once a vaccine becomes available, if we as a society play a role and get vaccinated, we certainly can contribute to ending the pandemic sooner rather than later. It looks like what we certainly need is antibodies that are of sufficient titer that can prevent disease and possibly protection, and the boosters seem to be doing it so far. ”
On Vaccine Boosters
“What are we trying to protect against with boosting? Are we trying to protect against a positive PCR? Is that a good strategy for us? Are we trying to prevent against severe disease and death? Then yes, we're getting out boosters that are going to be fine-tuned for what's circulating. But we also need to think about what are we boosting for, and maybe we need to change our perspective on that, as the virus has changed over time and likely will continue to surprise us again with another change.”
“We'll be learning (more about boosters) in the coming months as people in various countries are getting a fourth dose of the vaccine. And that information then will be used to determine how frequently people will need to get boosted. It's possible that after a fourth dose of an mRNA vaccine, that immunity could last for years.”
On Misperceptions About Vaccination
“Vaccines typically do not prevent infection. What they do is they prevent disease. It's important for people to understand that all of these breakthrough infections that we're seeing with omicron right now does not mean that the vaccines aren't working. When you look at the proportion of people who are getting seriously ill and dying, it's dropping. Even though the levels of immunity (from a vaccine) aren't adequate to protect from infection, because the immune system has seen it before, that immune response builds up really strong, really fast. And it kicks the virus out of the body before it can cause disease.”
“Now that said, HIV is an exception to that. The goal for an HIV vaccine is indeed to prevent infection altogether. And that's because HIV is such a different virus. Once a person gets infected, that virus integrates its genetic material into the infected cell. And you can't really get rid of it for an infected person. …So the goal there is to prevent infection altogether, which is setting a very high bar.”
“I think a lot of (people) are thinking along the lines of an HIV vaccine that we've been talking about for such a long time, where the viruses are totally different. For HIV, you need to have antibodies ready on exposure to prevent infection, because that's an irreversible process, versus COVID or influenza.”
On Progress Toward a "Pan-Coronavirus" Vaccine
“The first strategy is basically taking the coronavirus spike protein — this is the protein that allows the virus to infect the cells — and you can take the coronavirus spike proteins from multiple coronaviruses and we'll stitch those together into a chimeric protein that has different parts of different viruses. And this gives you a broad response that's capable of reacting with multiple coronaviruses. We at the DHVI have taken a different approach, which is to really focus in on the receptor binding domain, as this is the Achilles’ heel for coronavirus. This is a part that they need to be infectious. And then you can also broaden a response even more representing multiple receptor binding domains for multiple viruses.”
On How Duke's AIDS Work Informs Broader Discussions of Immunity
“We have cohorts here at Duke for people who are elite controllers. We have people naturally controlling HIV infection where they were, in the absence of (anti-retroviral therapy) for a decade or more, they were able to control a virus replication. We can look and see how are they doing that? What is their immune system? Can we recapitulate that with a vaccine regimen? And I think that speaks to my optimism for vaccines going forward, because I think the field has moved towards really trying to understand the biology of what's happening — that interaction of host and pathogen — and how we can guide the immune system.”
“You can do a comprehensive profile and get readouts of T-cell phenotype and function very easily, and different antibody features as well. And I think the other thing that has really helped the field is signatures of immunity. So doing gene expression analyses at baseline or post immunization or early time point that might predict a protective response, and all of those technologies are improving.”
“For years the HIV vaccine network had developed laboratory capabilities. We had the infrastructure in place, and we had the expertise, we have the technologies, and we just had to pivot to COVID and be able to monitor all of these immune responses. It's taken a while for the COVID vaccines field to actually catch up to HIV. HIV has been comprehensively evaluating immune responses for quite a while now.”
Meet the Experts
Colin S. Duckett, PhD, (moderator) is vice dean for basic science, professor of pathology, and interim chair of the Department of Pharmacology and Cancer Biology.
David Montefiori, PhD, is professor and director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences.
Kevin Saunders, PhD, is director of research at the Duke Human Vaccine Institute, associate professor of surgery, and assistant professor in the Department of Immunology and the Department of Molecular Genetics and Microbiology.
Georgia Tomaras, PhD, is the director of the Duke Center for AIDS research, a founding director of the Duke Center for Human Systems Immunology, a professor of surgery, immunology, and molecular genetics and microbiology.
Karl Leif Bates is the executive director of research communications at Duke University