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

doi:10.1016/j.celrep.2021.109664

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

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

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 language	English (US)
Article number	109664
Journal	Cell reports
Volume	36
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2021.109664
State	Published - Sep 7 2021

Funding

We thank Drs. Susan Weiss, Stanley Perlman, Thomas Gallagher, David Masopust, and Vaiva Vezys for discussions and reagents. This work was possible with startup funds to J.M.R. a grant from the Emerging and Re-Emerging Pathogens Program (EREPP) at Northwestern University to P.P.M. and a grant from the National Institute on Drug Abuse (NIDA, DP2DA051912) to P.P.M. T.D. and N.P. performed the immunogenicity experiments. J.C. performed the challenge experiments. P.P.M. and J.M.R. designed the experiments and secured the funding. P.P.M. and J.M.R. wrote the paper, with feedback from all of the authors. P.P.M. reports being Task Force Advisor to the Illinois Department of Public Health (IDPH) on SARS-CoV-2 vaccines. P.P.M. is also a member/advisor of the COVID-19 Vaccine Regulatory Science Consortium (CoVAXCEN) at Northwestern University's Institute for Global Health. We thank Drs. Susan Weiss, Stanley Perlman, Thomas Gallagher, David Masopust, and Vaiva Vezys for discussions and reagents. This work was possible with startup funds to J.M.R., a grant from the Emerging and Re-Emerging Pathogens Program (EREPP) at Northwestern University to P.P.M., and a grant from the National Institute on Drug Abuse (NIDA, DP2DA051912 ) to P.P.M.

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2021.109664

Cite this

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title = "Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2",

abstract = "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.",

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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