New vaccine design uses flu immunity to provide faster protection against emerging pathogens

After COVID vaccination, it typically takes weeks for our bodies to develop protective antibody responses. But imagine a vaccine that accelerates the production of antibodies against SARS-CoV-2, the virus that spreads COVID-19.

A research team led by Rong Hai, associate professor of microbiology and plant pathology at the University of California, Riverside, developed such a vaccine using pre-existing immunity to a distinct virus (the influenza virus) to help restart the antibody manufacturing process. against SARS-CoV-2.

“Any delay in the immune response to SARS-CoV-2 means there is a period of time when people are poorly protected against the virus,” Hai said. “Our vaccine is designed to speed up the protective response of antibodies, so that they are not vulnerable to the coronavirus. This is better protection for everyone. It could be particularly useful for people who still lack immunity against SARS-CoV-2, as children.”

The results of the study appear in the Journal of Virology.

To develop the new design, Hai and colleagues targeted SARS-CoV-2 as a representative pandemic virus and generated a “fusion protein” vaccine that combines the influenza A virus nucleoprotein and binding domain to the receptor, or RBD, of SARS. -CoV-2 spike protein. The SARS-CoV-2 virus uses the Spike protein to attach to a receptor on the surface of cells, the first step in the virus infecting the cell. Antibodies against the RBD block the interaction of the Spike protein with the receptor, preventing the virus from infecting the cell.

The new vaccine design addresses a long-standing challenge in the field of virology: the delay in the development of protective adaptive immunity against emerging viral pathogens. Hai explained that in any infection, antibodies are made by a type of cell called a B cell. Each B cell produces an antibody against a specific target; However, only a small subset of B cells can produce antibodies against RBD.

“For more B cells to become activated and start producing antibodies against the RBD, two steps are necessary,” said Harrison Dulin, first author of the paper and a former graduate student in Hai’s lab. “First, the B cell must encounter the RBD protein, and second, the B cell must be activated by another cell called a helper T cell. At the start of an immune response against SARS-CoV-2, there is no only a few helper T cells that can help activate RBD-specific B cells. This causes a delay in the mounting of the antibody response against the pathogen.

According to Hai, the new vaccine design has the advantage of allowing RBD-specific B cells to draw help from a pool of readily available helper T cells generated in response to influenza infection.

“Influenza helper T cells are harnessed to activate RBD-specific B cells, thereby speeding up the process of antibody production,” he said.

It is encouraging that the new design can be used even in countries with limited financial resources.

“Given the simplicity of our new design, it would not require these countries to acquire additional complicated or expensive equipment,” Hai said. “We designed the vaccine so that it can be administered in the same way as currently available vaccines.”

The new design stems from another project led by Hai, which aimed to design a dual vaccine platform against influenza and the SARS-CoV-2 virus. Although the research team only tested the vaccine against SARS-CoV-2, the new design can in principle be used to speed up antibody responses against other emerging pathogens.

“This could be particularly useful if we ever had to deal with SARS-CoV-3 or another new pandemic virus,” said co-author Emma H. ​​Wilson, professor of biomedical sciences in the School of Medicine. UCR.

Hai warned that more work needs to be done in the laboratory before the newly designed vaccine is made available to people.

“So far, we have only tested the vaccine on mice,” Hai said. “We need to explore, through clinical trials, whether this vaccine is safe for humans. It’s a long process. Additionally, pre-existing 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 settings to see how broadly applicable our strategy is.

The research project utilized the newly established Biosafety Level 3 (BSL-3) laboratory at UCR.

“We needed to show that the antibody responses produced by our vaccine could effectively neutralize live SARS-CoV-2,” Hai said. “As SARS-CoV-2 is a dangerous and highly contagious virus, working with active versions of the virus can only be done in BSL-3 laboratories.”

Hai, Wilson and Dulin were joined in the research by Duo Xu, Arrmund Neal, Edward Vizcarra, Jerald Chavez, Arzu Ulu, Keidy Wuang, Nikhil Bhakta and Chanvoraboth Chea of ​​UCR; and Ramya S. Barre, Myeon-Sik Yang, Siddiqur Rahman Khan, and Luis Martinez-Sobrido of the Texas Biomedical Research Institute in San Antonio. Dulin is now a postdoctoral researcher at the Fred Hutchinson Cancer Research Center, which focuses on infectious diseases.