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Just as the Pfizer Covid vaccine is granted full FDA approval, researchers are already working on the next generation of the protective formula.

A new and improved shot is already in the works, think of it as Covid vaccine 2.0. And local scientists like Northwestern Medicine Immunologist Dr Pablo Penaloza-Macmaster said it better protects against breakthrough infections.

“They are pretty effective in terms of preventing severe disease and death,” he said.

Covid vaccines work but Penaloza-Macmaster knows there’s room for improvement.

“Now with the incidence of breakthrough infections, we want to go the extra mile and think, ‘How can you make those vaccines even better?’” he said. “So not only protect you against severe disease and death but also protect you from getting the sniffles at all.”

Current formulas target the now ubiquitous spike protein. They’re easily recognizable to the immune system, which then mounts a response making antibodies against the invader.

“It’s kind of like the face of SARS-CoV-2, it’s kind of like the first thing the immune system sees,” he said.

But there is a potential target that sits inside the viral cell, the nucleocapsid is commonly found in coronaviruses. Hidden at first, it eventually emerges and sparks a rigorous immune response.

“In the initial phase, in the first hours of the infection the immune system cannot see the inside proteins,” Penaloza-Macmaster said. “But when the virus enters a cell and starts replicating and starts making all these proteins, then the infected cell starts getting decorated with all the different proteins — not only the surface proteins but the internal proteins. So, it’s a perfect target for T-Cell responses, which are cells in your immune system that go hunting for infected cells.”

The team tested their experimental vaccine – which includes the spike protein and the internal nucleocapsid — in mouse models. 

“We exposed the mice intranasally to SARS-CoV-2 and what we observed is that these mice were better protected against breakthrough infections,” Penaloza-Macmaster said. “And what this suggested is that the next generation of SARS-CoV-2 vaccines should also include internal proteins. So, the hope was, if you elicit responses not only to the external part of the virus but also the internal parts to this specific protein called nucleocapsid that you would improve protection.”

The next step is to try the new formula – which uses an adenovirus as a vector — in primates to confirm its effectiveness and to make sure it’s safe to begin human trials, which developers hope will happen in the next year. Doctors said this can be a booster for vaccinated people and an initial immunization for the unvaccinated.