In a Northwestern University study in mice, researchers took one of the current vaccines, which is based on the novel coronavirus' infamous spike protein, and added a different antigen, the nucleocapsid protein, to form a new, potentially improved version of the COVID vaccine.
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The scientists immunized mice with vaccines made from just the SARS-CoV-2 spike protein, just the nucleocapsid protein or both proteins combined. After several weeks, the researchers exposed the mice via their noses with SARS-CoV-2 and measured viral loads in the mice's respiratory systems or their nervous system 72 hours after exposure to capture a breakthrough infection.
They found that the nucleocapsid protein, which is an internal RNA-binding protein, may help kick the immune system into high gear much more quickly than the spike protein is capable of since it is among the most rapidly and highly expressed proteins in coronaviruses.
The well-known coronavirus spike protein is located outside the virus, whereas the nucleocapsid protein is present inside the virus. The nucleocapsid protein is one of the most rapidly and abundantly expressed proteins, making it the perfect target for early detection by the T cell response, said Pablo Penaloza-MacMaster, an assistant professor of microbiology-immunology at Northwestern University (NU) Feinberg School of Medicine.
He believes this is what made it so effective at preventing breakthrough infections in mice.
Another advantage of incorporating nucleocapsid in next-generation COVID vaccines is that this protein is more conserved or similar among SARS-CoV-2 variants and even among other coronaviruses, he said.
The researchers are still collecting data to determine whether vaccinated individuals who have a breakthrough COVID infection develop long-term neurological symptoms. In this study, they found evidence of viral infection in the brains of mice that were immunized with a current spike-based vaccine.
"I'm a little worried to see that the mice had viral loads in the brains because this suggests that perhaps with the current spike-based vaccines, these breakthrough infections could potentially get through to the brain," Penaloza-MacMaster said.
"We don't know if that's just in mice or whether it constitutes a general phenomenon. We're investigating that right now."
He hopes the new combination vaccine may better protect the brain from developing neurological symptoms if a breakthrough infection occurs.
The study was published Tuesday in the journal Cell Reports.
Northwestern Medicine is the collaboration between Northwestern Memorial HealthCare and Northwestern University Feinberg School of Medicine, which includes research, teaching and patient care. ■