Since the COVID-19 pandemic began, the Buck has been gathering evidence-based opinions and information from top researchers and thinkers about the science aimed at bringing it to an end. What are the biggest takeaways so far? How close are we to getting back to normal? Everyone, from molecular biologists and epidemiologists to clinicians and public health experts, has been remarkably consistent on a few key points. Don’t have time to listen to eleven hour-long conversations? No problem! We’ve assembled the highlights from these webinars in a 4-part series. This is the final blog in our series. You can access the first, about research into the virus itself, here, the second, about public health measures, here, and the third, about risk factors and therapeutics, here.
Part 4
Vaccines and Immunity
The whole world has been getting a crash course in the immune system and vaccine development over the past 5 months. Our experts provide some key insights and takeaways about how the immune system, immune protection, potential vaccines, and therapeutics are all interacting right now in the fight against COVID-19, and how they predict vaccine development will continue to unfold.
What is the immune system up to?
John Newman, Assistant Professor at the Buck and Practicing Geriatrician: Inflammation is a good thing when our body is using it to heal ourselves. … But when inflammation gets uncontrolled and can’t get turned off, that causes problems. So older people’s immune systems are in this strange state where they’re always a little bit too active and causing this inflammation, but then they have a hard time ramping up when they’re supposed to, to fight a virus.
Eric Verdin, President and CEO of the Buck Institute: Since no one is immune to this virus, we are all relying on this initial innate defense, which you might think is actually a good thing. If it’s hyperactive we should be more protected. It’s a good thing, initially, but it becomes a problem later in the infection, because we think this is what actually often causes the death, is this overactive immune response.
A duet between the virus and the immune system
Warner Greene, Director of the Gladstone Center for HIV Cure Research: The first phase is dominated by the virus and the second phase is dominated by the host. So when people initially get infected the virus is in control. It’s trying to multiply and replicate. At the point when people get so sick that they need to go to the hospital, they have now entered the phase of the disease that is driven by the host. And now the host is mounting an overly zealous response against the virus, rich in inflammation, and this leads to what’s called a cytokine storm, and, ultimately, to the acute respiratory distress syndrome.
We’re still trying to figure out what “immunity” means
EV: The way we can [identify who has already been infected] is by looking for these antibodies. The antibodies come from the adaptive immune system; it is an educated immune response that is specific for the virus. They have the ability to latch onto the virus and to neutralize it. We can detect them in the blood of people who have been infected. Typically, for most viruses these antibodies indicate immunity which means that you are actually protected from a super infection.
Larry Brilliant, Chairman of Ending Pandemics: So looking at the family of coronaviruses and looking at one, two, or three years of immunogenicity, I think it’s reasonable to start off with the beginning assumption that this virus will provide immunity, something like that. Maybe it will only produce several months of immunity, but I think the fear that it will produce no immunity, there’s no real evidence I think to support that…Just said a different way, if you want to get one year of immunity for the average person, then that virus is not going to come back and see you as a customer for another year.
Matt Willis, Marin County Public Health Officer: So this is my situation. I was infected, recovered, I had anybody testing twice now, and it’s been positive. But what science cannot tell me yet is does that confer true immunity?
Kevin Tracey, President and CEO, Feinstein Institutes for Medical Research: There’s a tremendous amount of questions on what does immunity to this disease mean? And does it develop in all patients who have had the disease, or some? Is it a B-cell antibody-based immunity, or a T-cell protection that may be important? We don’t understand that yet.
Melanie Ott, Director of the Gladstone Institute of Virology: I have to tell you that we don’t know what is happening and how protective the immunity will be, and whether we can tell people with positive serology or a positive history that they are not going to become infected again and they will not be spreading the virus to somebody else again.
WG: It’s not clear how long the durability of a vaccine will last. For example, the flu vaccine, we have to change it every year to match the virus. It’s circulating. Sometimes we get it right, sometimes we don’t get it quite right. Hopefully, the SARS-CoV-2 vaccine will last for a number of years, but it’s possible that we may have to get vaccinated more frequently. It probably will not be like a measles vaccine where, you know, one vaccination lasts you for a lifetime.
Everything, including the good news, is unprecedented:
LB: So we’re doing something that’s never been done in science, and I love it…the usual process for getting a vaccine ready to produce is in series, in sequence. We usually do safety trials, efficacy trials, and efficiency trials. And every one of those takes about six months, or whatever they take. That’s where the one year to 18 months to get a vaccine usually comes from. But we’re doing all those in parallel, too. Every suggested vaccine we’re doing safety and efficacy tests in parallel right now, which is just wonderful. So I’m aspirational that we will have a vaccine that produces better immunity than the disease, and we will have it in the time period that Tony Fauci said, 12 to 18 months from now.
MO: I think we are actually at an enormous pace, currently, with the vaccine development compared to other vaccines that we have developed in the past that have taken years to do. But here, basically we take the genomic information, inject it, and then let the body do all the work. This is a wonderful concept and it was extremely fast, and that’s why people talking about maybe having something [soon].
Sue Desmond Hellmann, Former Chief Executive Officer, Bill & Melinda Gates Foundation: One thing that gives me hope is the product development innovation. There are over 130 vaccines in trials, and the level of science… there’s RNA, DNA, adenovirus vectors. It’s incredible that a lot of the new things we’ve been excited about are actually leading the way in vaccines against coronavirus. And it’s not crazy to think that we will at least have some answers by the end of the year, if not a vaccine that can start to go into use. So I’m very positive about the vaccines, and the work that’s going on in vaccines.
Robert Redfield, Director, Centers for Disease Control and Prevention: The one thing I can say, as someone who’s been in vaccine development since, you know, probably 1981, a variety of vaccines over my life, I’ve never seen anything move faster. It’s refreshing.
It’s a good thing vaccine research is gong so fast, because we really need it
WG: I think the ultimate solution is a vaccine. And there, the news is so far so good. We have three companies moving into phase two/phase three efficacy trials: Moderna in July, Oxford and AstraZeneca in August, and Johnson and Johnson in September, and others… you know, many, many others that are closely following thereafter. We’re going to need four, five, six different vaccines, and all manufactured at scale, in order to vaccinate the billions of people who are going to need the vaccine.
RR: You know, it’s clear that this, you know, first experience is really going to still leave over 75% of the American public susceptible to this virus. So we do need the biological countermeasure. Otherwise, we’re going to have to go through two or three years of wrestling with this virus, and I just would like to get it behind us.
Even with the speed, safety remains imperative
SDH: I will say one of the good news items is that there’s been so much publicity about a vaccine for COVID that the people I talk to are really hyper about safety. They are really hyper about safety. They are making sure that they see every patient in the trial, that they answer every question, that they pick the right dose.
RR: The CDC is going to play a big role in monitoring all the side effects and toxicities of this vaccine, as is done, and we’re making sure we’re doing that for the whole vaccine program. But I don’t want people to misunderstand what we’re accelerating, you know, when you said Project Warp Speed. So what’s going fast? Are we skipping steps? We’re not skipping any scientific integrity steps, and we’re not going to be skipping safety.
Vaccines or therapeutics? Yes, please
Nevan Krogan, Director of the Quantitative Biosciences Institute at UCSF: At the end of the day, it’s probably going to be a mixture of approaches that will be brought to bear to help out here. And it could be, with respect to therapeutic approaches, maybe a drug and an antibody or something, or maybe there will be a vaccine for a certain subgroup and there’ll be a therapeutic for another subgroup of individuals that are older or don’t respond to the vaccine. So that’s why it’s so important to keep pushing on the research on all fronts, because you don’t know what’s going to break out and be the most useful.
This is the final blog of takeaways in our webinar series so far. As the pandemic rolls on, we will continue to share evidence-based information, updates, and insights with you.