Assessing the news about COVID-19 vaccines: A Q&A with Dr. Lynda Stuart

Pfizer and BioNTech recently announced their COVID-19 vaccine has shown 95% effectiveness in a readout of its late-state clinical trial. Moderna declared their own vaccine candidate was 94.5% effective in an early readout from similar trials. We spoke with Dr. Lynda Stuart, lead of the foundation’s COVID-19 Discovery and Translational Vaccine Response team, about these initial findings and what they mean for the development and delivery of COVID-19 vaccines going forward.

These results are really exciting and super important, for several reasons.

First, we didn’t know going in whether a COVID-19 vaccine was even possible. These results demonstrate that, in fact, it is absolutely possible to protect people from COVID-19 with a vaccine. That gives us a lot of hope not only for these two candidates but for other vaccines being developed.

Second, it wasn’t known if the right part of the virus was being targeted. All six of the leading vaccine candidates are targeting the spike protein—which in the COVID-19 diagrams is the red spike sticking out of the gray ball. So to know this is in fact the right target is very reassuring. Both Pfizer and Moderna are getting a strong immune response, and that means other vaccine candidates using this protein as the antigen will likely also be effective.

Of course, it’s way too early to declare victory. We still haven’t seen the safety or efficacy data from these two candidates. It will also be important to determine these vaccines’ durability, meaning how long they work, and also whether they interrupt transmission, meaning do they stop you from spreading COVID-19 if you’re infected. But the underlying science seems right, and that should give everyone a sigh of relief. We’re not talking about a five-year window on a vaccine anymore. There should be more than one approved next year.

These trials will continue for up to two years to assess both the vaccines’ safety and durability, and the study participants involved will be followed for a long time. In parallel, we expect that the companies will soon submit their trial data to gold-standard regulators like the FDA for approval and licensure. The regulators will determine in a rigorous and unbiased way whether the vaccines work and if they are safe. In time, it will become clear how long they are able to protect for.

This is incredibly good scientific news. But, to be clear, this alone isn’t going to solve the pandemic. Multiple vaccines are needed just to get the number of doses that will be needed to protect seven billion people. Our delivery team often reminds us that vaccines themselves don’t save lives, it’s the immunizations—the actual shots—and so it is important to also set up supply chains so vaccines can get to everyone who needs them.

No, we did not invest directly in either Pfizer or BioNTech for their COVID-19 vaccine. The companies took on the risk for the R&D themselves.

That said, we do have an ongoing partnership with BioNtech. In September 2019, we invested $55 million in their company because we thought that the mRNA technology they were developing had great potential and broad applicability to fighting global infectious diseases like TB and HIV. So we wanted to help build their capacity to work on HIV immunotherapies and TB vaccines. These types of program-related investments are a really important tool we can use to help companies to take on risk and to work in neglected areas where there is not a large market. Even during the pandemic, they have continued that work—they have remained amazingly committed to HIV and TB and have been fantastic partners throughout this year despite being very busy with COVID-19. It should be noted that all profit made from any foundation investment is spent on a charitable purpose.

We did not play a role in their COVID-19 research. We have been funding CEPI (the Coalition for Epidemic Preparedness Innovations), and Moderna was a CEPI grantee at the very earliest stages of their work. We have provided grants to Moderna over the years on other diseases, such as HIV.

These first two vaccine candidates are also the first-ever mRNA vaccines that have gone into large efficacy studies. mRNA vaccines have been a foundation priority for some time.

Normally, to vaccinate somebody, you create some part of the virus or bacteria that you want to mount an immune response to in a lab, purify it, and inject it into a patient. But with mRNA, you bypass that manufacturing step. Instead, you just inject messenger RNA into the body. It provides the genetic information so your body itself makes a negligible and non-infectious piece of the virus and then targets an immune response to it. Then if you’re exposed to the virus, your body is already familiar with it and that immunological memory protects you when you get infected.

We are long-term proponents of mRNA vaccines because they show such enormous promise. As we’ve seen in the past year, they are very flexible and make it possible to go from a standing start to a vaccine much more quickly.

The other exciting thing is they elicit not only the B cells’ antibody response, but also a cellular immune response. This flexibility means they can be used to protect from different types of pathogens, including ones that evolve or change over time. This is transformational. With further study, it could eventually mean new immunotherapies and even cures for diseases like the universal flu, TB, and HIV, on top of COVID-19.

For the end user, there is no difference. They'll appear exactly like any other vaccine in a plastic syringe. What is different or difficult with mRNA vaccines right now is their stability at different temperatures.

For example, the Pfizer vaccine requires ultracold chain storage—it needs to be stored at minus 80 degrees centigrade so there's no breakdown in its potency. Imagine having to store the vaccines in dry ice at every step of the distribution process. The Moderna vaccine doesn't have to kept be quite as cold, but it also requires a cold chain of its own, as do many other kinds of vaccines.

Given the delivery issues and supply chain complications this creates globally—even in the U.S.—access could be really expanded if companies developed thermally stable options for the vaccine. But it will probably take some development time—six months or a year—to get those improvements.

We are also working in lower- and middle-income countries to see if we can bolster the cold chain where it’s needed. This is clearly a big challenge, though. That’s why the next wave of vaccines is also critically important, as they are likely not to need such cold temperatures to stay stable.

As I said, the world will need many vaccines just to get everybody vaccinated. There is a big difference between a $1 a dose vaccine and a $10 a dose vaccine if you're trying to vaccinate seven billion people, especially if—like the Pfizer and Moderna candidates—they require two doses. While mRNA vaccines are amazing, they’re likely not yet affordable or practical for wide-spread use in low- and middle-income countries, in part because of the cold chain.

Assuming the science works out, some of the other major vaccine candidates that could be available early next year—like those by Novavax, Johnson & Johnson, and AstraZeneca/Oxford—will have less stringent cold chain requirements that can help them travel to more remote areas.

We are also funding CEPI to advance “wave 2” vaccine candidates and invested somewhere in the range of $20 million directly into smaller companies like SK Biosciences in South Korea and Bio-E and Serum Institute in India to develop vaccine candidates that are better optimized for the conditions needed for worldwide distribution. These are more thermostable, should offer protection to a wider range of people, can be manufactured at existing factories, and most importantly, should cost less.

How do we stop COVID-19 from continuing to be widespread in certain areas around the world? How do we stop outbreaks and protect everybody, not just the wealthy who can afford it? Ultimately, 50-70% of the world’s population will need to take the vaccine if we want to disrupt COVID-19 transmission chains. That’s the goal I think we need to target as a planet.

Absolutely. As I said, we don't yet know whether these vaccines block transmission—maybe they just stop you from getting sick. So before getting the vaccine, everybody should be wearing a mask. And after getting the vaccine, everybody should continue to wear a mask.

I actually think there may be a compounding effect of vaccinations and masks. When you add them together they may decrease the spread even faster, and the public health teams can start focusing more closely on efforts like contact tracing and really helping infected patients with better therapeutics and treatments.

I would like to just call out what I think has been an amazing and collaborative ecosystem in the scientific community. Pharmaceutical companies always have a level of competition, which is normal. But there has been a phenomenal spirit of collaboration and open data sharing. It's been really refreshing to see. If we can bring the same spirit of openness to other global health problems like HIV, TB, and so on after we deal with COVID-19, I think it will make a profound difference. How we continue to foster to this level of collaboration for other global health challenges is something we are actively addressing.