Researchers at the University of California (UC), Riverside have developed a novel vaccine that leverages existing immunity to the influenza virus to speed the development of antibodies against SARS-CoV-2, the virus that causes COVID-19. In the study, published this week in the Journal of Virology, they note that the same approach could also be used against other emerging pathogens.
The approach, uses what investigators call a “fusion protein” that combines the nucleoprotein from influenza A virus and the receptor-binding domain (RBD) of the spike protein on SARS-CoV-2. The first step in infection by SARS-CoV-2 is the virus using the spike protein to attach to a receptor on the cell surface. Antibodies against RBD block the binding of the spike protein with the receptor, preventing it from infecting the cell.
According to Rong Hai, PhD, associate professor of microbiology and plant pathology at UC Riverside, the novel vaccine design addresses what is a known long-standing challenge in developing more effective vaccines: the delay in developing protective adaptive immunity for emerging viral pathogens.
“Any delay in the immune response to SARS-CoV-2 means there is some time when people are left poorly protected against the virus,” said Hai. “Our vaccine is designed to get people those protective antibody responses faster, so they are not vulnerable to the coronavirus. This is better protection for everyone. It could be especially valuable for people who still lack immunity to SARS-CoV-2, such as children.”
Hai noted that in any infection antibodies are produced by B cells and that each B cell produces one antibody against a specific target. However, only a fraction of B cells produce antibodies against RBD.
First author and former student in the Hai Lab Harrison Dulin said that two steps are required for B cells to actively produce antibodies against RBD: “First, the B cell needs to encounter the RBD protein, and second, the B cell needs to be activated by another cell called a helper T cell. At the start of an immune response against SARS-CoV-2, there are only a few helper T cells around that can help activate the RBD-specific B cells. This causes a delay in mounting the antibody response against the pathogen.”
But the new vaccine is designed to allow the RBD-specific B cells to get help from a pool of helper cells boosted by the response to the influenza A infection. “The flu helper T cells are harnessed to activate the RBD-specific B cells, speeding up the process of antibody production,” Hai said.
Of further benefit, he noted that the simplicity of the novel design could also easily be deployed in low resources countries, as production does not require a complex production process or expensive equipment. The method of administration is also the same as existing vaccines.
The development of the novel vaccine built on work in Hai’s lab, aimed at creating a vaccine platform that could immunize for both influenza and SARS-CoV-2. While it has only been tested in mouse models to date, the team believes its discovery can provide a platform for speedy response against other emerging pathogens in the future.
“So far, we have only tested the vaccine in mice,” Hai concluded. “We need to explore through clinical trials if this vaccine is safe for humans. It’s a long process. Further, preexisting immunity to influenza can vary from person to person, and we know that immune responses can wane over time. We need to test this vaccine in a range of immune backgrounds to see how widely applicable our strategy is.”