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Can a Vaccine for Covid-19 Be Developed in Record Time? by Siddhartha Mukherjee

In the history of medicine, rarely has a vaccine been developed in less than five years. Among the fastest to be developed was the current mumps vaccine, which was isolated from the throat washings of a child named Jeryl Lynn in 1963. Over the next months, the virus was systematically “weakened” in the lab by her father, a biomedical scientist named Maurice Hilleman. Such a weakened or attenuated virus stimulates an immune response but does not cause the disease; the immune response protects against future infections with the actual virus. Human trials were carried out over the next two years, and the vaccine was licensed by Merck in December 1967.

Antiviral drugs, too, have generally taken decades to develop; effective combinations of them take even longer. The first cases of AIDS were described in the early 1980s; it took more than a decade to develop and validate the highly effective triple drug cocktails that are now the mainstay of therapy. We are still continuing to develop new classes of medicines against H.I.V., and notably, there is no vaccine for that disease. And yet the oft-cited target for creating a vaccine against SARS-CoV-2, the virus that causes Covid-19, is 12 months, 18 at the outside.

Pulling that off is arguably the most important scientific undertaking in generations. The Times assembled (virtually, of course) a round table to help us understand the maddening complexity of the challenge and the extraordinary collaboration it has already inspired. The group included a virologist; a vaccine scientist; an immunologist and oncologist; a biotech scientist and inventor; and a former head of the Food and Drug Administration.

The Panelists

Siddhartha Mukherjee is an associate professor of medicine at Columbia University and a cancer physician and researcher. He is the author of “The Emperor of All Maladies: A Biography of Cancer,” which was the winner of the 2011 Pulitzer Prize in general nonfiction, and “The Gene: An Intimate History.” He was recently appointed to Gov. Andrew Cuomo’s blue-ribbon commission to reimagine New York.

Dan Barouch is the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston and a professor of medicine at Harvard Medical School.

Margaret (Peggy) Hamburg is the foreign secretary of the National Academy of Medicine. She was commissioner of the Food and Drug Administration from 2009 to 2015.

Susan R. Weiss is a professor and vice-chairwoman of the Department of Microbiology at the University of Pennsylvania and a co-director of the Penn Center for Research on Coronaviruses and Other Emerging Pathogens.

George Yancopoulos is co-founder, president and chief scientific officer of Regeneron.



Photo illustration by Mike McQuade

What It Takes to Find a Vaccine

George Yancopoulos: Most people don’t realize that successfully inventing and developing any new drug or vaccine is quantifiably among the hardest things that human beings try to do. This is reflected in the numbers. Although there are thousands of major medical institutions and thousands of biotech and biopharma companies that collectively involve millions of researchers and hundreds of billions of dollars invested per year — and all are working on new vaccines and medicines — the vast majority of efforts fail, with the F.D.A. only approving 20 to 50 new medicines a year. And each of the rare success stories usually occurs over many years, often a decade or two.

Peggy Hamburg: So with Covid-19, we are moving at record speed, in terms of the history of vaccine development.

Siddhartha Mukherjee: Can you put a number down for how quickly we can get an effective vaccine developed? Is the 12-to-18-month time frame we’ve been hearing realistic?

Dan Barouch: The hope is that it will be within a year, but that is not in any way guaranteed. That projection will be refined as time goes on — and a year assumes that everything goes smoothly from this point forward. That’s never been done before. And safety cannot be compromised.

Hamburg: Realistically, the 12 to 18 months that most people have been saying would be a pretty good marker but still optimistic.

Susan R. Weiss: I’d agree.

Mukherjee: To think about whether there’s any way to make this process go faster, let’s start by talking about how the search for a vaccine usually happens. Dan, what is the general principle of what a vaccine is and how it works?

Barouch: The goal of a vaccine is to raise an immune response against a virus or a bacterium. Later, when a vaccinated person is exposed to the actual virus or bacterium, the immune system will then block or rapidly control the pathogen so that the person doesn’t get sick. The immune cells that make antibodies are called B cells. Once they’ve been triggered by a vaccine to raise an immune response, some of these B cells can last for years and are always standing ready to make antibodies against the pathogen when it is encountered, thereby protecting against the disease for a prolonged period of time.

Hamburg: Under normal conditions, drug-and-vaccine development begins with “preclinical” work — basic science — to identify the nature of the disease in question.

Weiss: In virology labs like mine, we try to identify the viral proteins that a vaccine might target, usually the protein that recognizes and attaches to the host-cell receptor. All coronaviruses have a so-called spike protein, which is what gives the virus its corona-like morphology, the “crownlike shape,” as can be visualized in an electron microscope. To invade a cell, the spike protein attaches to a receptor — another protein, usually — on the cell’s outer membrane. This eventually results in the genetic material of the virus, in this case, an RNA protein complex, being internalized in the cell. And once that happens, replication can begin and a person can get sick. If you can identify the viral protein that interacts with the cellular receptor, then you can try to create a vaccine. This spike protein represents a particularly attractive candidate for a vaccine, because it is a protein that most prominently sticks outside of the surface of the virus, and so it’s the part of the virus that is most visible to the immune system.

Mukherjee: So what are the different approaches that you can take to finding vaccines?

Barouch: A tried-and-true vaccine approach is a whole inactivated virus vaccine — that’s when you grow up the actual virus in the laboratory, for example in cells or in eggs, and then “inactivate” it with chemicals or another method to make it unable to infect cells but still able to elicit an immune response. A company in China, Sinovac Biotech, currently has an inactivated SARS-CoV-2 vaccine in clinical trials. The pros are that there’s a long clinical history of multiple vaccines that have been successful in that regard, such as the inactivated polio vaccine and the inactivated flu vaccine. The cons are that there are always some safety considerations around proving that the virus has been fully inactivated. If the virus is not fully inactivated, the danger is that it might actually cause the disease.