One Year In: Vaccines

COVID-19 vaccine experts talk lessons learned, challenges ahead

Two women in white coats and surgical masks hold syringes labeled "COVID-19 vaccine"
Staff at Brigham and Women’s Hospital prepare to administer COVID-19 vaccine doses. Image: James Rathmell

This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education, and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

In the last 12 months, COVID-19 has overturned both individual lives and national economies.

Yet the pandemic has also sparked advances in scientific knowledge, treatments, and vaccines at a pace never before seen. Instead of the usual five to 10 years, the first clinical trial of a vaccine against SARS-CoV-2 began a mere six months after scientists sequenced the virus's genome.

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Two vaccines so far have been authorized for emergency use by the U.S. Food and Drug Administration. More than 31 million doses have been distributed and more than 12 million have been administered to people as of Jan. 15, according to the CDC. Doctors and researchers are studying 68 additional vaccine candidates in human clinical trials around the world.

Among those who have pushed the boundaries of vaccine science to address the global health crisis are the researchers at Harvard Medical School, in the greater Boston area, and at Guangzhou University in China who came together last March to form the Massachusetts Consortium on Pathogen Readiness, or MassCPR.

As the first anniversary of MassCPR approaches, Harvard Medicine News spoke with the co-leads of its vaccine working group about the striking accomplishments in COVID-19 vaccine development, what we’ve learned so far, and what lies ahead.

Head shot of a man in a white coatCo-lead Dan Barouch, the William Bosworth Castle Professor of Medicine at HMS and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, designed a vaccine platform that delivers the SARS-CoV-2 spike protein in deactivated adenovirus (common cold) shells and trains the immune system to recognize the invader. He conducted the lab dish and animal model studies that established the promise of the vaccine, called Ad26, and is now co-running an international clinical trial in conjunction with Johnson & Johnson.

Head shot of a manCo-lead Andrea Carfi is vice president and head of research for infectious disease at Moderna, a Cambridge-based biotechnology company that developed one of the FDA-approved COVID-19 vaccines. That vaccine stimulates immunity using messenger RNA (mRNA), which teaches cells to make and attack harmless pieces of the SARS-CoV-2 spike protein so the body is primed to fight future infection.

HM News: In a nutshell, what has the working group been doing over the past year?

Barouch: The working group is a discussion forum for outstanding scientists in academia, industry, and other areas with expertise in all aspects of COVID-19 vaccines. We meet online every two weeks to discuss the latest advances in immunology, virology, and vaccine science as well as vaccine development, regulatory approvals and distribution, ethics, and social-political-societal dimensions.

Andrea and I keep the group up to date with the Moderna and J&J vaccines; Luk Vandenberghe shares news about his AAV [adeno-associated virus] vaccine; and there are some protein-based vaccines people have been working on. There’s been a lot of vaccine science and immunology: Bruce Walker has his sample acquisition cohort, Steve Elledge has VirScan to look at viral epitopes, Galit Alter has systems serology. Many people are involved in vaccine immunology, which dovetails with vaccine development.

And there are many other topics. We have a philosopher and ethicist who’s been active in framing questions about human challenge models [clinical trials in which willing participants are deliberately exposed to COVID-19], equitable vaccine distribution, racial and ethnic issues, how to recruit participants into trials, and vaccine skepticism. We talk about some of the political issues and the international side of vaccination. Equity has been a major topic within our group and in the field as a whole in the past year and doubtless will be in the coming year as well.

HM News: How is this different from how science normally works?

Carfi: People are more willing to share research and resources without thinking about the priority of publication or being scooped. I’ve been impressed by people’s openness in sharing data and collaborating. This is reflected in publications with many different labs involved. Dan and I had never worked together before, and now we have a review paper coming out in March. People know more about what other groups are doing. We have greater insight into the field’s progress and challenges. It’s been very productive.

If we can keep people this engaged, we will have an advantage in the future for other viruses, vaccines, and pandemics.

Barouch: Part of the community spirit has been based on the tremendous need for understanding a brand-new virus and the sheer global urgency to develop treatments and vaccines. That commonality of purpose brought people together in a way I’ve never seen. It’s the same on an international scale and in other COVID-related communities focused on therapeutics, pathogenesis, politics, implementation, and so forth. The enormity of the challenge and the sense of shared purpose has certainly facilitated sharing of unpublished data and plans.

HM News: Alongside this spirit of collaboration and sense of urgency, what do you think has contributed to vaccines against COVID-19 being developed in record time?

Carfi: There was large investment and commitment by government, regulatory agencies, and the academic community, including Harvard. We are talking both financial and intellectual resources. Being able to share infrastructure, labs, and animal models helped us move quickly.

All these vaccines couldn’t have moved to the clinic without having the basic science understanding behind them. Safety comes first, and a lot of experiments and preclinical data needed to be generated about how these new platforms—mRNA and adenovirus delivery—act at the molecular level. You need to know what you’re doing. Science provides the base to advance, and to advance quickly.

HM News: Does success in the COVID-19 realm mean we’ll see other vaccines reach fruition faster in the future?

Barouch: Going from gene sequencing to completion or near completion of phase 3 in a year is really unprecedented. It is possible to do again, but there has to be an enormous, urgent global need and a huge number of resources available. Under normal circumstances, there wouldn’t be those two factors. I also don’t think it’s humanly possible to sustain this level of intensity on a continuous basis.

That said, the mechanisms of collaboration where people see that talking to one another and sharing information leads to better outcomes for everyone will have long-lasting implications.

I think vaccine development won’t go as slowly as before. People won’t present to a company’s boardroom with a 10-year timeline. The COVID-19 vaccines will change how the vaccine world operates.

Carfi: I agree that it’s a special feature of the pandemic. The crisis brought everyone together to tackle the same question. The hope is that that collaboration will continue, both because I don’t think COVID is going away in a few months, and because we hope to expand [our new communal philosophy] to other research areas. We’ve created a team that hopefully can be applied in future.

Barouch: Our hope is certainly that elements of the MassCPR collaboration and infrastructure can be there for the next pathogen that comes through.

The COVID-19 vaccines will change how the vaccine world operates. 

Dan Barouch

William Bosworth Castle Professor of Medicine, HMS

All these vaccines couldn’t have moved to the clinic without having the basic science understanding behind them.

Andrea Carfi

Vice president and head of research for infectious disease, Moderna

We’re definitely not in a position to claim victory yet. We’re in the beginning of the next chapter. 

Dan Barouch