Clinical trials are now underway to test vaccine candidates for COVID-19. Lindsey Baden, MD, an infectious diseases specialist at the Brigham and an expert in vaccine development for viral diseases, and his team and colleagues from across the Brigham and beyond, have been working diligently to pave a path for launching large-scale clinical trials rapidly and safely. In late July, recruitment for the phase 3 COVE study began at 89 clinical sites, including the Brigham. The COVE study will evaluate mRNA-1273, a vaccine candidate against COVID-19 manufactured by Moderna, Inc., of Cambridge, Mass.
Baden and a panel of experts in research, clinical care and health equity led a forum for clinicians at the end of July to address questions on the minds of both clinicians and their patients. The panel discussed various vaccine platforms in development, strategies for vaccine acceleration, equity and disparities in vaccine research, clinical trials and access, and the Brigham’s role in vaccine trials. Below are some of the highlights from the conversation, which have been edited for length and clarity.
Most vaccines take years, if not decades, to be developed. How can we be certain a vaccine against COVID-19 is safe?
LB: As clinicians, we have to make safety assessments all the time and it’s rarely black and white. For example, most of us think of penicillin as a safe, life-saving drug, but in rare cases, it can cause a patient to go into anaphylaxis or develop a life-threatening mucocutaneous condition known as Stevens-Johnson syndrome. We prescribe antibiotics because the benefit outweighs the risk of the side effect.
We don’t yet know the long-term consequences of COVID-19. We’ve only been caring for patients with COVID for about six months. This makes it challenging to weigh the safety concerns of the treatment against the safety risks posed by the disease, but I think the initial data we’ve seen on vaccine safety suggests that, theoretically, there should be limited safety concerns about a vaccine. Through phase 3 clinical trials, we should generate data on tens of thousands of individuals. But we won’t know safety issues that may occur in one in a million or one in a hundred thousand until we have studied that number of people.
I think that safety will have to be an ongoing consideration for vaccines against COVID-19. In my view, it’s always balanced against the potential benefit. We’ll need to vigorously monitor and assess for safety concerns, but if we had a vaccine that we knew worked at protecting against COVID-19, given what we are seeing across the country and the globe, then we can build the safety data set while we try to tackle the pandemic.
Is the NIH-Moderna trial directly exposing patients to the virus that causes COVID-19 or is the assumption that they will be exposed through community interactions? And how will participants be assessed for COVID-19?
LB: I want to be clear that participants will not be exposed to the virus through the vaccine. There is a very interesting debate scientifically about so-called challenge studies, but that’s an entirely different concept. For the NIH-Moderna trial of the vaccine candidate mRNA-1273, and other phase 3 trials under Operation Warp Speed (OWS), this is not the case. The NIH-Moderna vaccine candidate itself does not contain live virus — it’s an mRNA construct. You cannot get COVID-19 from it, full stop. The way that a participant may contract COVID-19 is through interactions in the community. The hope is that the vaccine will decrease risk of acquiring COVID-19 from normal community interactions or work interactions, or that the vaccine will decrease severity of symptoms.
If a participant has COVID symptoms or flu-like symptoms, we will test them for COVID-19. And presumably those who received the active vaccine will have less diagnosed COVID-19 than those who have placebo. We’ll test whenever symptoms or illness that could be a respiratory virus emerge.
Should we be concerned about whether the money already being poured in to vaccine production will affect the final decision on whether to push through and make the vaccines available to the public?
LB: On the scientific side, absolutely not. Obviously, there are political forces at play, but the data, the science should guide us. And if the data clearly demonstrate activity, I think we should all react to that. If the data don’t, we should all be circumspect. I do think it is worth some investment [to manufacture millions of doses of each of the vaccines being tested through OWS] to save six to 12 months so that if something works, we don’t have to wait another year. The financial risk is modest in the context of a trillion-dollar catastrophe, but the data should guide whether or not we move forward.
If someone participates in this trial, does that preclude them from getting a vaccine that is more effective or gets approved?
LB: Participation in these studies don’t preclude best care for a patient. As knowledge advances, and we determine what does work or what doesn’t, we will stop doing what doesn’t work and figure out how to deploy what does. These studies hopefully will enable us to know what works, and if something emerges, then we need to consider how we act equitably to distribute a vaccine across society, including individuals who are participating in these studies. All of us feel very strongly that best care and best therapeutic option should be given to people who participate in these studies.
Will people need to get a COVID-19 vaccine annually? How effective will it be at preventing infection from other strains of coronavirus?
LB: We’ve known about COVID for six months, so it’s very hard for us to predict too far into the future, and we don’t even have efficacy data yet. COVID is not the flu so I have a feeling it won’t behave like the flu. We need to do the science to really understand the viral evolution in relation to the immune response elicited by the vaccines.