We should soon have a better idea. A handful of trials are now under way to test the power of vaccine combinations, with the first results due in later this month. If these mixed regimens prove safe and effective, countries will be able to keep the vaccine rollout moving even if supplies of one vaccine dwindle because of manufacturing delays, unforeseen shortages, or safety concerns.
But there’s another, more exciting prospect that could be a vital part of our strategy in the future: mixing vaccines might lead to broader immunity and hamper the virus’s attempts to evade our immune systems. Eventually, a mix-and-match approach might be the best way to protect ourselves.
Mixing on trial
The covid-19 vaccines currently in use protect against the virus in slightly different ways. Most target the coronavirus’s spike protein, which it uses to gain entry to our cells. But some deliver the instructions for making the protein in the form of messenger RNA (Pfizer, Moderna). Some deliver the spike protein itself (Novavax). Some use another harmless virus to ferry in the instructions for making it, like a Trojan horse (Johnson & Johnson, Oxford-AstraZeneca, Sputnik V). Some offer up whole inactivated virus (Sinopharm, Sinovac).
In a study published in March, researchers from the National Institutes for Food and Drug Control in China tested combinations of four different covid-19 vaccines in mice, and found that some did improve immune response. When they first gave the rodents a vaccine that relies on a harmless cold virus to smuggle in the instructions and then a second dose of a different type of vaccine, they saw higher antibody levels and a better T-cell response. But when they reversed the order, giving the viral vaccine second, they did not see an improvement.
Why combining shots might improve efficacy is a bit of a mystery, says Shan Lu, a physician and vaccine researcher at the University of Massachusetts Medical School who pioneered this mixing strategy. “The mechanism we can explain partially, but we don’t fully understand.” Different vaccines present the same information in slightly different ways. Those differences might awaken different parts of the immune system or sharpen the immune response. This strategy might also make immunity last longer.
Whether those results translate to humans remains to be seen. Researchers at Oxford University have launched a human trial to test just how mixing might work. The study, called Com-CoV, offers participants a first shot of Pfizer or Oxford-AstraZeneca. For their second dose, they will either get the same vaccine or a shot of Moderna or Novavax. The first results should be available in the coming weeks.
Other studies are under way as well. In Spain, where Oxford-AstraZeneca is now being given only to people over 60, researchers plan to recruit 600 people to test whether a first dose of the shot can be paired with a second dose from Pfizer. According to reporting in El País, about a million people received the first dose of the vaccine but aren’t old enough to receive the second dose. Health officials are waiting for the results of this study before issuing recommendations for this group, but it’s not clear whether any participants have yet been recruited.
Late last year Oxford-AstraZeneca announced that it would partner with Russia’s Gamaleya Institute, which developed Sputnik V vaccine, to test how the two shots work in combination. The trial was supposed to launch in March and provide interim results in May, but it’s not clear whether it has actually begun. And Chinese officials have hinted that they’ll explore mixing vaccines to boost the efficacy of their shots.
The biggest gains might come from mixing vaccines that have lower efficacies. The mRNA vaccines from Pfizer and Moderna provide excellent protection. “I don’t think there’s reason to mess with that,” says Donna Farber, an immunologist at Columbia University. But mixing might improve protection for some of the vaccines that have reported lower levels of protection, like Oxford-AstraZeneca and Johnson & Johnson, as well as some of the Chinese vaccines. Many of these vaccines work quite well, but mixing might help them work even better.
Donald ’67, SM ’69, and Glenda Mattes
Don Mattes started giving to the Picower Institute for Learning and Memory at MIT before he himself was diagnosed with Alzheimer’s disease. Since his death in 2020, his wife, Glenda, has carried forward Don’s passion for its work. “My wish is that no one ever has to go through the horrors of Alzheimer’s disease ever again,” Glenda says. The Matteses have also supported the Koch Institute for Integrative Cancer Research at MIT.
Legacy sparks hope. An early key employee of Andover Controls who later ran the company’s European operations, Don visited six continents with Glenda during their 30-year marriage—often to ski or bicycle. “Don’s was a life well lived, just too short,” Glenda says. The couple made provisions in their estate plan to support the Picower Institute. After Don died, Glenda made a gift to MIT of real estate that established both endowed and current-use funds there to support research on Alzheimer’s, dementia, and other neurodegenerative diseases. Glenda is a cancer survivor, and the gift also endowed a fund in the couple’s name at the Koch Institute.
Great discoveries being made at MIT: “Don always said the best thing he got from MIT was being taught how to think,” Glenda says. “MIT is an amazing place. Picower Institute director Li-Huei Tsai and her team are doing more than looking for a treatment for Alzheimer’s. They’re looking for the root cause of the disease. I am also fascinated with the Koch’s melding of engineering and biology. The chances they are going to solve the cancer issue someday are very high.”
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Investing in women pays off
“Starting a business is a privilege,” says Burton O’Toole, who worked at various startups before launching and later selling AdMass, her own marketing technology company. The company gave her access to the HearstLab program in 2016, but she soon discovered that she preferred the investment aspect and became a vice president at HearstLab a year later. “To empower some of the smartest women to do what they love is great,” she says. But in addition to rooting for women, Burton O’Toole loves the work because it’s a great market opportunity.
“Research shows female-led teams see two and a half times higher returns compared to male-led teams,” she says, adding that women and people of color tend to build more diverse teams and therefore benefit from varied viewpoints and perspectives. She also explains that companies with women on their founding teams are likely to get acquired or go public sooner. “Despite results like this, just 2.3% of venture capital funding goes to teams founded by women. It’s still amazing to me that more investors aren’t taking this data more seriously,” she says.
Burton O’Toole—who earned a BS from Duke in 2007 before getting an MS and PhD from MIT, all in mechanical engineering—has been a “data nerd” since she can remember. In high school she wanted to become an actuary. “Ten years ago, I never could have imagined this work; I like the idea of doing something in 10 more years I couldn’t imagine now,” she says.
When starting a business, Burton O’Toole says, “women tend to want all their ducks in a row before they act. They say, ‘I’ll do it when I get this promotion, have enough money, finish this project.’ But there’s only one good way. Make the jump.”
Preparing for disasters, before it’s too late
All too often, the work of developing global disaster and climate resiliency happens when disaster—such as a hurricane, earthquake, or tsunami—has already ravaged entire cities and torn communities apart. But Elizabeth Petheo, MBA ’14, says that recently her work has been focused on preparedness.
It’s hard to get attention for preparedness efforts, explains Petheo, a principal at Miyamoto International, an engineering and disaster risk reduction consulting firm. “You can always get a lot of attention when there’s a disaster event, but at that point it’s too late,” she adds.
Petheo leads the firm’s projects and partnerships in the Asia-Pacific region and advises globally on international development and humanitarian assistance. She also works on preparedness in the Asia-Pacific region with the United States Agency for International Development.
“We’re doing programming on the engagement of the private sector in disaster risk management in Indonesia, which is a very disaster-prone country,” she says. “Smaller and medium-sized businesses are important contributors to job creation and economic development. When they go down, the impact on lives, livelihoods, and the community’s ability to respond and recover effectively is extreme. We work to strengthen their own understanding of their risk and that of their surrounding community, lead them through an action-planning process to build resilience, and link that with larger policy initiatives at the national level.”
Petheo came to MIT with international leadership experience, having managed high-profile global development and risk mitigation initiatives at the World Bank in Washington, DC, as well as with US government agencies and international organizations leading major global humanitarian responses and teams in Sri Lanka and Haiti. But she says her time at Sloan helped her become prepared for this next phase in her career. “Sloan was the experience that put all the pieces together,” she says.
Petheo has maintained strong connections with MIT. In 2018, she received the Margaret L.A. MacVicar ’65, ScD ’67, Award in recognition of her role starting and leading the MIT Sloan Club in Washington, DC, and her work as an inaugural member of the Graduate Alumni Council (GAC). She is also a member of the Friends of the MIT Priscilla King Gray Public Service Center.
“I believe deeply in the power and impact of the Institute’s work and people,” she says. “The moment I graduated, my thought process was, ‘How can I give back, and how can I continue to strengthen the experience of those who will come after me?’”