Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2

Tanushree Dangi, Jacob Class, Nicole Palacio, Justin M. Richner*, Pablo Penaloza MacMaster*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


SARS-CoV-2 infection causes respiratory insufficiency and neurological manifestations, including loss of smell and psychiatric disorders, and can be fatal. Most vaccines are based on the spike antigen alone, and although they have shown efficacy at preventing severe disease and death, they do not always confer sterilizing immunity. Here, we interrogate whether SARS-CoV-2 vaccines could be improved by incorporating nucleocapsid as an antigen. We show that, after 72 h of challenge, a spike-based vaccine confers acute protection in the lung, but not in the brain. However, combining a spike-based vaccine with a nucleocapsid-based vaccine confers acute protection in both the lung and brain. These findings suggest that nucleocapsid-specific immunity can improve the distal control of SARS-CoV-2, warranting the inclusion of nucleocapsid in next-generation COVID-19 vaccines.

Original languageEnglish (US)
Article number109664
JournalCell reports
Issue number10
StatePublished - Sep 7 2021


  • COVID-19
  • SARS-CoV-2 vaccines
  • nucleocapsid antigen
  • spike antigen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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