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

免疫 Spike(软件开发) 病毒学 免疫系统 生物 免疫学 中和 严重急性呼吸综合征冠状病毒2型(SARS-CoV-2) 医学 疾病 病毒 2019年冠状病毒病(COVID-19) 病理 传染病(医学专业) 管理 经济 内科学
作者
Jae‐Kwan Kim,A. V. Kachko,Prabhuanand Selvaraj,David S. Rotstein,Charles B. Stauft,Naveen K. Rajasagi,Yangqing Zhao,Tony T. Wang,Marian Major
出处
期刊:npj vaccines [Nature Portfolio]
卷期号:10 (1)
标识
DOI:10.1038/s41541-025-01085-1
摘要

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.
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