At the March 16 daily press briefing by the White House Coronavirus Task Force, Anthony Fauci, M.D., seemed excited in his buttoned-down way. This was before Fauci, director of the National Institute of Allergy and Infectious Diseases, became a household name; before millions of Americans grew familiar with his gravelly, Brooklyn-accented voice and carefully qualified statements; and well before Brad Pitt played him on “Saturday Night Live.”
Fauci told reporters and the TV audience that earlier that day, thefirst volunteer for a phase 1 trial of a candidate vaccine against COVID-19 had been injected. The volunteer was later identified as Jennifer Haller, an operations manager at a tech company in Seattle.“You might recall when we first got started that I said it would be two to three months, and if we did that, that would be the fastest we had ever gone from obtaining the sequence (of a virus) to being to a phase 1 trial,” Fauci said, with President Donald Trump standing to his left at a pre-social-distancing distance. “This has now been 65 days, which I believe is the record.”
Now it seems like that record was for the first 100 meters of what may turn into a full, 26.2-mile marathon. Fauci has since said repeatedly in interviews that it will probably be a year or more before a COVID-19 vaccine is not only tested but also deemed both safe and effective.
“It isn’t just the timetable. It has to be safe and it has to be effective,” Fauci said in an inter-view with a Canadian TV network.
As Fauci tapped the brakes, some vaccine developers raced ahead, raising hopes that more records would be set. At the end of April, CanSino Biologics, a Chinese company, said it was poised to start a phase 2 trial of its vaccine and would enroll 500 people in Wuhan, China, where the pandemic started.
Vaccine developers at Oxford University in England were going at an unheard-of speed. They collapsed the normally sequenced phase 1 safety and phase 2 efficacy trials into a single trial designed to enroll more than 500 volunteers. And as we went to press, they were gearing up for a phase 2/3 trial that would include 5,000 volunteers.
An inviting target
By some accounts, there are 86 COVID-19 vaccine candidates; by others, 115. In those two tallies, and in every other reasonable count, the vast majority of the COVID-19 vaccine candidates are in a preclinical stage and not ready to be tested in people. “There will be fierce attrition,” wrote Derek Lowe in his widely read blog for Science Translational Medicine. “and only a few (low single digits) will make it deep into the process.”
As COVID-19 vaccine kicked into gear, Regulatory Focus, the online publication of the Regulatory Affairs Professionals Society, started a helpful COVID-19 vaccination tracker to keep tabs on. At the end of April, the tracker listed one COVID-19 candidate, the bacillus Calmette-Guerin vaccine used primarily against tuberculosis, in as being in a phase 2/3 trials, six in phase 1, 10 in preclinical development, and 27 in a catchall “research in additional vaccine candidate” category.
In many ways, SARS-CoV-2, the virus that causes COVID-19, is an inviting target for a vaccine. Because of today’s powerful sequencing technology and prior experience with other coronaviruses, the RNA genome of the virus was sequenced quickly, giving researchers a handle on the virus’s reproduction and the encoding of its spherical outer shell, including those now-familiar spikes that give it the menacing look of the head of a medieval mace.
For vaccine developers, those spikes, called S proteins, are something of a dream come true because they are the means by which the virus binds to and infects cells, and antibodies that home in on and stick to S proteins can block that process. Many of the current crop of vaccines are designed to deliver this S protein (or a fragment of it) to trigger an immune response and unleash antibodies that will fend off future infection by SARS-CoV-2.
Vaccine developers also seem to have a relatively stable target in SARS-CoV-2. Decades of research into vaccines for HIV and hepatitis C have come up empty-handed partly because those viruses are elusive shape-shifters.