Evidence map›Paper›PMID 39948345›Full record

ArticleNPJ vaccines2025

Combined immunization with SARS-CoV-2 spike and SARS-CoV nucleocapsid protects K18-hACE2 mice but increases lung pathology.

Jaekwan Kim, Alla Kachko, Prabhuanand Selvaraj, David Rotstein, Charles Brandon Stauft, Naveen Rajasagi, Yangqing Zhao, Tony Wang, Marian Major

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jaekwan KimDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Alla KachkoDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0003-1366-1900
Prabhuanand SelvarajDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0001-7266-3928
David RotsteinDivision of Food Compliance, Center for Veterinary Medicine, Food and Drug Administration, Rockville, MD, USA.ORCID http://orcid.org/0000-0001-7438-2281
Charles Brandon StauftDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0001-5633-2950
Naveen RajasagiDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Yangqing ZhaoDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Tony WangDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0001-8983-1721
Marian MajorDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. marian.major@fda.hhs.gov.

Funding

U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration) Z01 BK 04010-11 LHV
6 · The paper itself

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.

Identifiers

PMID39948345
PMCPMC11825953

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.