The group hopes to build a vaccine targeting infants, as well. “Infants can get infected and can have bad outcomes, but also they can spread the infection to others,” Levy said.
Their work is supported by National Institute of Allergy and Infectious Disease.
In the labs of Mahmoud Nasr and Gerhard Wagner, the Elkan Blout Professor of Biological Chemistry and Molecular Pharmacology at HMS, researchers have just started work on what’s called a subunit vaccine. In these vaccines, scientists only use the essential antigens from a virus, said Nasr, a principal investigator in the renal division and division of engineering in medicine at Brigham and Women’s Hospital.
Wagner and Nasr hope to create a vaccine where several copies of the coronavirus spike proteins are placed in large phospholipid nanodiscs that can elicit a strong antibody response by mimicking the large number of spikes of the virus and their position in a membrane. It has been shown that presenting numerous antigens on a membrane environment produces a stronger response than using non-membrane-bound proteins. This method will likely require adjuvants and multiple doses to elicit a strong enough immune response that provides long-term immunity.
At Harvard’s Wyss Institute for Biologically Inspired Engineering, researchers hope to create bioactive material that cues a stronger immune response against the coronavirus. They hope the vaccine both kills the virus in infected individuals and helps uninfected individuals develop longer-lasting immunity without the need for additional boosts. Led by David Mooney, a Wyss core faculty member and the Robert P. Pinkas Family Professor of Bioengineering at Harvard John E. Paulson School of Engineering and Applied Sciences, the team previously created cancer vaccines that prompted the immune system to attack and destroy cancer cells. Other efforts at the Wyss focus on diagnostics and therapeutics.
In a related effort, researchers at HMS’s Blavatnik Institute and at the Brigham hope to use an antibody-detection tool called VirScan — which they adapted to recognize antibodies for the novel coronavirus in people’s blood — to help scientists working on vaccines identify which viral antibodies the immune system best responds to and which don’t affect the virus.
“[VirScan] can help you follow a vaccine to see how well it’s making antibodies and what kinds of antibodies,” said Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine at HMS and Brigham and Women’s, who developed the tool in 2015 with two Ph.D. candidates in his lab. “A lot of the antibodies you make are just useless. They don’t do anything to the virus or hurt the virus and they don’t help it. They’re just neutral. They’re there. Sometimes they even make it easier for the virus to get into certain cell types … The idea would be that you would try to remove them from the vaccine, because they’re competing with the neutralizing antibodies in the vaccine just as much as they would be with the actual virus.”
While he hopes this effort takes off, Elledge’s primary focus is on using VirScan as a post-infection tool to study the outbreak’s true extent, lethality, and epidemiology, and learn how the virus affects the immune system.
For Barouch, having multiple coronavirus vaccine-related efforts are crucial, since no one group has all the expertise and each vaccine will have pros and cons.
“We don’t yet know which vaccine is ultimately going to be the safest, the most effective, and the most deployable,” Barouch said. “Ultimately, if we have two or more vaccines that become available for COVID-19, that would be a good thing because each vaccine is different. For example, some vaccines might be very effective in the elderly; some might not. Some might be easier to produce at mass scale; some might not. Some might be single-dose regimens, some might be multiple-dose regimens. Each vaccine is going to have its own particular characteristics.”