Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology
Abstract Vaccines against SARS-CoV-2 have targeted the spike protein and have been successful at preventing disease. However, with the emergence of variants, spike-specific vaccines become less effective. The nucleocapsid protein is relatively conserved among variants of SARS-CoV-2 and is a candidat...
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Nature Portfolio
2025-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01085-1 |
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| author | Jaekwan Kim Alla Kachko Prabhuanand Selvaraj David Rotstein Charles Brandon Stauft Naveen Rajasagi Yangqing Zhao Tony Wang Marian Major |
| author_facet | Jaekwan Kim Alla Kachko Prabhuanand Selvaraj David Rotstein Charles Brandon Stauft Naveen Rajasagi Yangqing Zhao Tony Wang Marian Major |
| author_sort | Jaekwan Kim |
| collection | DOAJ |
| description | Abstract Vaccines against SARS-CoV-2 have targeted the spike protein and have been successful at preventing disease. However, with the emergence of variants, spike-specific vaccines become less effective. The nucleocapsid protein is relatively conserved among variants of SARS-CoV-2 and is a candidate for addition to spike in next generation vaccines for the induction of T cell protection. Previous studies on SARS-CoV have suggested that the induction of an immune response to nucleocapsid could result in enhanced disease. Using the K18-hACE2 mouse model we investigated immunization with a variant nucleocapsid, from SARS CoV (N1) alone or in combination with spike from SARS-CoV-2 and compared this to nucleocapsid from SARS-CoV-2 (N2). The spike-nucleocapsid-based vaccines conferred protection against SARS-CoV-2 in lungs and brain and decreased lung pathology compared to control mice. However, higher T and B cell immune responses were observed in N1-immunized mice prior to challenge, whether delivered alone or with spike, and immunization with N1 resulted in increased lung pathology compared to immunization with spike or N2. These findings suggest that spike-nucleocapsid-based vaccines are safe and effective, even with variant nucleocapsid sequences, but that viral control in this mouse model may be associated with higher lung pathology, compared to spike immunization alone, due to the immunogenic qualities of the nucleocapsid antigen. |
| format | Article |
| id | doaj-art-50418b1eaf4646948713d1bbd8aafc1a |
| institution | DOAJ |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-50418b1eaf4646948713d1bbd8aafc1a2025-08-20T02:43:10ZengNature Portfolionpj Vaccines2059-01052025-02-0110111210.1038/s41541-025-01085-1Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathologyJaekwan Kim0Alla Kachko1Prabhuanand Selvaraj2David Rotstein3Charles Brandon Stauft4Naveen Rajasagi5Yangqing Zhao6Tony Wang7Marian Major8Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Food Compliance, Center for Veterinary Medicine, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationAbstract Vaccines against SARS-CoV-2 have targeted the spike protein and have been successful at preventing disease. However, with the emergence of variants, spike-specific vaccines become less effective. The nucleocapsid protein is relatively conserved among variants of SARS-CoV-2 and is a candidate for addition to spike in next generation vaccines for the induction of T cell protection. Previous studies on SARS-CoV have suggested that the induction of an immune response to nucleocapsid could result in enhanced disease. Using the K18-hACE2 mouse model we investigated immunization with a variant nucleocapsid, from SARS CoV (N1) alone or in combination with spike from SARS-CoV-2 and compared this to nucleocapsid from SARS-CoV-2 (N2). The spike-nucleocapsid-based vaccines conferred protection against SARS-CoV-2 in lungs and brain and decreased lung pathology compared to control mice. However, higher T and B cell immune responses were observed in N1-immunized mice prior to challenge, whether delivered alone or with spike, and immunization with N1 resulted in increased lung pathology compared to immunization with spike or N2. These findings suggest that spike-nucleocapsid-based vaccines are safe and effective, even with variant nucleocapsid sequences, but that viral control in this mouse model may be associated with higher lung pathology, compared to spike immunization alone, due to the immunogenic qualities of the nucleocapsid antigen.https://doi.org/10.1038/s41541-025-01085-1 |
| spellingShingle | Jaekwan Kim Alla Kachko Prabhuanand Selvaraj David Rotstein Charles Brandon Stauft Naveen Rajasagi Yangqing Zhao Tony Wang Marian Major Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology npj Vaccines |
| title | Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology |
| title_full | Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology |
| title_fullStr | Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology |
| title_full_unstemmed | Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology |
| title_short | Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology |
| title_sort | combined immunization with sars cov 2 spike and sars cov nucleocapsid protects k18 hace2 mice but increases lung pathology |
| url | https://doi.org/10.1038/s41541-025-01085-1 |
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