Decades later, when SARS hit, researchers including Hotez began working on a vaccine. But in early tests with lab animals, they saw something that raised a red flag. The animals’ immune cells were attacking their lungs, causing damage like that which had been described in the RSV trials. “That alerted everyone in the coronavirus research community, that there was potential for immune enhancement,” says Hotez. His group, which includes collaborators from the New York Blood Center, adapted its strategy. Instead of producing the entire spike protein, they built just a tiny piece of it—the piece that actually latches on to human cells, called the receptor binding domain. With this approach, Hotez says, when they tested in animals they saw immune protection but without the undesirable enhancement.
The prototype vaccine they developed wasn’t able to attract any investment after the SARS outbreak dissipated. But now, the group is currently submitting proposals to fund human testing of the vaccine, which has been sitting in a freezer in Texas since the mid-2000s. Because the virus that causes Covid-19 uses the same receptor as SARS to attack human lung cells, they believe it might offer some protection. But it will be important to come up with a clinical trial design that includes additional, longer-term monitoring of patients to watch out for potential immune enhancement. Hotez says any vaccines designed to fend off Covid-19 will likely have to do the same. “That’s going to really complicate things and slow them down,” he says. “I don’t think anyone’s going to have something ready in 12-18 months.”
Who’s Making a Covid-19 Vaccine?
Almost everyone! Here’s a breakdown of the 30+ candidates in development (so far), starting with those who are making nucleotide-based vaccines.
Boston-based biotech unicorn Moderna is perhaps best known for working on personalized cancer vaccines. But the company has a history of responding to public health threats, including the 2015 Zika outbreak. In collaboration with scientists at the National Institutes of Allergy and Infectious Disease, and with funding from CEPI, Moderna has already produced an RNA-based vaccine which codes for a stabilized form of the SARS-CoV-2 spike protein. On February 24, the company shipped doses of its candidate, mRNA-1273, to the NIAID Vaccine Research Center, where a Phase I safety trial is set to begin as early as April.
Like Moderna, crosstown rival CureVac uses lab-made mRNA to spur the production of coronavirus proteins, triggering immune cells to produce antibodies against it. And, like Moderna, it got a grant from CEPI to apply its technology to SARS-CoV-2. CureVac representatives have said the company expects to have a candidate ready for human testing within a few months.
This Pennsylvania-based biotech uses a slightly different technology, using DNA instead of RNA to make medicines. It has also received funding from CEPI to develop a DNA-based vaccine against Covid-19. In January, the company started preclinical testing of its candidate, called INO-4800. It has so far produced 3,000 doses for trials to be conducted in patients in the US, China, and South Korea. The first of these is scheduled to begin in the US at the end of April.
Applied DNA Sciences / Takis Biotech
Applied DNA, a New York-based company, announced in March it is partnering with Rome, Italy-based Takis Biotech to deliver its own DNA-based vaccine candidates against Covid-19. The companies plan to have four versions available to test in mice by later this month.
India-based pharmaceutical firm Zydus Cadila announced in February it had initiated two approaches for developing a Covid-19 vaccine. Like Inovio and Applied DNA, the first involves using a ring of DNA designed to produce coronavirus protein once inside the human body. The second deals with genetically manipulating an attenuated recombinant measles virus so that it will induce antibodies against Covid-19. Company officials have not announced timelines for human testing.