Pfizer and BioNTech, the duo behind the world’s most widely used COVID-19 vaccine, and one of the most successful pharmaceutical products of all time, are developing a trio of vaccines that could spur stronger, broader, and longer-lasting immunity to the coronavirus.
BioNTech chief executive Dr. Ugur Sahin and chief medical officer Dr. Özlem Tureci — the husband and wife leaders of the German biotech company that partnered with Pfizer to develop the COVID-19 vaccine Comirnaty — said in an interview that clinical trials of all three new shots are expected to begin over the next six months.
During a visit to the company’s US offices in Cambridge on Friday, the couple emphasized the pandemic isn’t over because new variants are still emerging. “This virus will stay with us for many years, and we are still in the pandemic phase of this outbreak,” Sahin said. “So all of the predictions that the pandemic will [soon] be over are just not true.”
The company’s plans for multiple next-generation vaccines come as millions are rolling up their sleeves for updated booster shots tailored to the Omicron variants of the virus. US and European regulators authorized BioNTech, Pfizer, and their competitor, Moderna, to begin distributing those new boosters about a month ago.
So far, about 11.5 million people have received one of the new boosters in the United States, according to the Centers for Disease Control and Prevention, suggesting that demand for each subsequent booster shot is waning. About two-thirds of Americans have gotten at least two shots, and only about one-third have gotten at least one booster shot.
BioNTech made $21 billion from sales of that shot in 2021 and expects to earn $15 billion to $20 billion from them this year. And although biotech analysts anticipate sales of COVID shots will drop significantly in 2023, BioNTech is doubling down on new-and-improved versions of its vaccine.
The company hasn’t disclosed technical details about these three new shots, but Sahin told the Globe about the rationale behind each one.
The first new vaccine, which BioNTech and Pfizer recently began testing in people, contains a version of the coronavirus spike protein with a tweaked structure — dubbed “Superspike” — that Sahin hopes will help people’s immune systems make higher levels of neutralizing antibodies. “It exposes the region of the spike protein which is recognized by antibodies in a more prominent fashion,” he said.
A second new vaccine is intended to strengthen the T cell response, a branch of the immune system that the current mRNA vaccines are just so-so at stimulating. While antibodies are best known for blocking viral infections, T cells are good at stopping infections already in progress. “T cells can limit the infection and help to clear the infection much faster,” Sahin said.
Many immunologists have argued that T cells could help lower the risk of developing severe disease, or potentially even reduce mild illnesses by nipping infections in the bud. Crucially, T cells are good at recognizing parts of the coronavirus that mutate much less frequently than the spike protein, meaning that T cell immunity might hold its ground even as new variants emerge. A clinical trial of a vaccine focused on boosting T cell immunity will start within two months, Sahin said.
BioNTech’s third, and potentially most ambitious, new vaccine uses an engineered spike protein that the company hopes will spur broadly neutralizing antibodies that can tackle multiple variants of the coronavirus, including ones we’ve never seen before.
Some researchers have called this approach a pan-coronavirus vaccine, but Sahin said he doesn’t like that name, since he thinks it is unrealistic to make a vaccine that protects against all coronaviruses.
“The idea here is to focus the immune response into regions that are more conserved in the spike protein,” Sahin said. These are the vulnerable regions of the spike that don’t mutate as much, but that our immune systems are not great at spotting on their own. BioNTech hopes to start a clinical trial of the vaccine in about six months.
Sahin and Tureci said that BioNTech is also prepared to update the booster shots to match a specific variant again, if necessary. “We will continue to monitor any upcoming new variants,” Tureci said. “We have an [artificial intelligence]-based early warning system with which we screen upcoming variants,” she added. The firm also tests antibodies obtained from the blood of vaccinated people against variants of concern to see if the virus is escaping the immune system.
At the beginning of 2020, BioNTech had about 1,300 employees. That number swelled to more than 3,000 by the end of 2021, although the company’s US presence is small. BioNTech has 205 people in its Cambridge offices and labs, a short walk from the Central Square MBTA Red Line stop.
The site includes staff from the former immunotherapy company Neon Therapeutics, which BioNTech acquired for $67 million in early 2020. The site focuses largely on cancer, infectious disease, and clinical trial development in the United States. BioNTech has a slightly smaller location employing about 145 people in Gaithersburg, Md.
“Boston is one of the key areas, maybe the key area, for biotechnology talent,” Sahin said. BioNTech plans to grow its presence in the Boston area, Sahin said, but he wouldn’t share specifics. “We want to build a strong US leadership team to ensure that we can continue to develop our technologies, continue to do clinical trials in the region, and acquire talent.”