Pub Date : 2026-02-01Epub Date: 2026-01-06DOI: 10.1111/imcb.70072
Deborah L Burnett, Ania Moxon, Anupriya Aggarwal, Katherine Jl Jackson, Catherine Cotter, Anouschka Akerman, Amanda Russell, Rachel Kalman, David Langley, Jake Y Henry, Daniel Christ, Rowena A Bull, Robert Brink, Anthony D Kelleher, Hans-Martin Jäck, Stuart Turville, Bernard Moss, Christopher C Goodnow
Long-lasting protective immunity against sarbecoviruses is hampered by the dominance of elicited antibodies to variable parts of the Spike protein, allowing ongoing viral escape and evolution. We investigated Modified Vaccinia Ankara (MVA) vaccine candidates expressing the SARS-CoV-1 or SARS-CoV-2 Spike for their ability to induce antibodies targeting different epitopes on the SARS-CoV-2 Receptor Binding Domain (RBD), including those with wide variant conservation. We also explored the capacity of these different Spike proteins to induce broad cross-reactive or cross-neutralizing B cells against multiple variants. This revealed that the SARS-CoV-1 Spike induced distinct patterns of epitope dominance compared to the traditional SARS-CoV-2 Spike antigens. Following immune imprinting by previous exposure to ancestral SARS-CoV-2 Spike, the epitope dominance patterns induced by SARS-CoV-1 and SARS-CoV-2 vaccines still differed, with most of the germinal center response consisting of de novo recruited B cells. In addition to the de novo response, B cells with germline cross-reactivity to both antigens further increased their binding toward the most recently immunized antigen. Interestingly, we found that, while SARS-CoV-2 vaccinated animals were extremely capable of mounting an antigen-specific germinal center and plasmablast response to a booster immunization with SARS-CoV-1, SARS-CoV-2 boosters were less capable of inducing SARS-CoV-2 specific B cells following prior SARS-CoV-1 vaccination. These findings have broad implications for the implementation of vaccine strategies against emerging coronavirus variants and potential future coronavirus spillover events. The implications stemming from a fundamental directionality of immune imprinting and epitope dominance may have wider implications for noncoronavirus antigens.
{"title":"Humoral epitope dominance and immune imprinting by SARS-CoV-1 and SARS-CoV-2 vaccines.","authors":"Deborah L Burnett, Ania Moxon, Anupriya Aggarwal, Katherine Jl Jackson, Catherine Cotter, Anouschka Akerman, Amanda Russell, Rachel Kalman, David Langley, Jake Y Henry, Daniel Christ, Rowena A Bull, Robert Brink, Anthony D Kelleher, Hans-Martin Jäck, Stuart Turville, Bernard Moss, Christopher C Goodnow","doi":"10.1111/imcb.70072","DOIUrl":"10.1111/imcb.70072","url":null,"abstract":"<p><p>Long-lasting protective immunity against sarbecoviruses is hampered by the dominance of elicited antibodies to variable parts of the Spike protein, allowing ongoing viral escape and evolution. We investigated Modified Vaccinia Ankara (MVA) vaccine candidates expressing the SARS-CoV-1 or SARS-CoV-2 Spike for their ability to induce antibodies targeting different epitopes on the SARS-CoV-2 Receptor Binding Domain (RBD), including those with wide variant conservation. We also explored the capacity of these different Spike proteins to induce broad cross-reactive or cross-neutralizing B cells against multiple variants. This revealed that the SARS-CoV-1 Spike induced distinct patterns of epitope dominance compared to the traditional SARS-CoV-2 Spike antigens. Following immune imprinting by previous exposure to ancestral SARS-CoV-2 Spike, the epitope dominance patterns induced by SARS-CoV-1 and SARS-CoV-2 vaccines still differed, with most of the germinal center response consisting of de novo recruited B cells. In addition to the de novo response, B cells with germline cross-reactivity to both antigens further increased their binding toward the most recently immunized antigen. Interestingly, we found that, while SARS-CoV-2 vaccinated animals were extremely capable of mounting an antigen-specific germinal center and plasmablast response to a booster immunization with SARS-CoV-1, SARS-CoV-2 boosters were less capable of inducing SARS-CoV-2 specific B cells following prior SARS-CoV-1 vaccination. These findings have broad implications for the implementation of vaccine strategies against emerging coronavirus variants and potential future coronavirus spillover events. The implications stemming from a fundamental directionality of immune imprinting and epitope dominance may have wider implications for noncoronavirus antigens.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"150-167"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Small nucleolar RNAs (snoRNAs) contribute to ribosome biogenesis and modulate various aspects of plant growth and development. Given that osmotic stress downregulates numerous genes associated with ribosome biogenesis in roots, we hypothesize that snoRNAs might function in modulating plant responses to osmotic and drought stresses. To prove this hypothesis, we assessed the role of a C/D-box snoRNA, namely the HIDDEN TREASURE 2 (HID2), in Arabidopsis thaliana responses to drought using both loss-of-function and overexpression approaches. Under drought conditions, the Arabidopsis hid2 mutant displayed a significantly higher survival rate than both wild-type (WT) and HID2-complemented plants, while HID2-overexpressing plants showed a lower survival rate than WT. A series of physiological assays indicated that the hid2 mutant maintained a slower rate of water loss and more intact cell membranes than WT plants under drought, which supported their drought-tolerant phenotype. Comparative leaf transcriptome and proteome analyses revealed that processes related to wax biosynthesis, senescence, and anthocyanin accumulation were differentially regulated between hid2 and WT plants under water-deficit conditions. Consistently, the hid2 mutant accumulated higher amounts of wax and anthocyanins and exhibited delayed leaf senescence relative to WT plants under drought. Additionally, the hid2 mutant showed improved ability to increase sensitivity to abscisic acid (ABA), scavenge reactive oxygen species (ROS), and extended root hairs. Overall, these findings demonstrate HID2's role as a negative modulator in Arabidopsis drought tolerance by negatively affecting cell membrane stability, wax and anthocyanin biosynthesis, senescence, ROS-scavenging capacity, ABA responsiveness, and root hair formation.
{"title":"Small nucleolar RNA HIDDEN TREASURE 2 reduces drought tolerance via multiple pathways in Arabidopsis.","authors":"Liangliang Li, Xianpeng Yang, Haodong Huang, Chenbo Zhu, Minghui Xing, Kaixin Yang, Xiaofan Nie, Jiahe Fu, Mingming Wang, Zhengwei Liang, Xianzhong Feng, Jiuhai Zhao, Xiangnan Li, Shiyou Lü, Yong Shi, Lam-Son Phan Tran, Xiaojian Yin, Weiqiang Li","doi":"10.1111/tpj.70718","DOIUrl":"https://doi.org/10.1111/tpj.70718","url":null,"abstract":"<p><p>Small nucleolar RNAs (snoRNAs) contribute to ribosome biogenesis and modulate various aspects of plant growth and development. Given that osmotic stress downregulates numerous genes associated with ribosome biogenesis in roots, we hypothesize that snoRNAs might function in modulating plant responses to osmotic and drought stresses. To prove this hypothesis, we assessed the role of a C/D-box snoRNA, namely the HIDDEN TREASURE 2 (HID2), in Arabidopsis thaliana responses to drought using both loss-of-function and overexpression approaches. Under drought conditions, the Arabidopsis hid2 mutant displayed a significantly higher survival rate than both wild-type (WT) and HID2-complemented plants, while HID2-overexpressing plants showed a lower survival rate than WT. A series of physiological assays indicated that the hid2 mutant maintained a slower rate of water loss and more intact cell membranes than WT plants under drought, which supported their drought-tolerant phenotype. Comparative leaf transcriptome and proteome analyses revealed that processes related to wax biosynthesis, senescence, and anthocyanin accumulation were differentially regulated between hid2 and WT plants under water-deficit conditions. Consistently, the hid2 mutant accumulated higher amounts of wax and anthocyanins and exhibited delayed leaf senescence relative to WT plants under drought. Additionally, the hid2 mutant showed improved ability to increase sensitivity to abscisic acid (ABA), scavenge reactive oxygen species (ROS), and extended root hairs. Overall, these findings demonstrate HID2's role as a negative modulator in Arabidopsis drought tolerance by negatively affecting cell membrane stability, wax and anthocyanin biosynthesis, senescence, ROS-scavenging capacity, ABA responsiveness, and root hair formation.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"125 3","pages":"e70718"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-25DOI: 10.1111/imcb.70075
Jiawen Lyu, Guangming Gong, Long Feng
This study, from the perspective of a Medical Immunology student, sought to explore and investigate the implementation of the Academic Tutor System in the teaching of Medical Immunology. The characteristics and challenges of studying Medical Immunology, as well as the limitations of conventional teaching models in this discipline, are analyzed. Additionally, the concept and theory of the Academic Tutor System and its application in the learning process of medical students are introduced in this study. Moreover, the specific implementation methods of the Academic Tutor System in Medical Immunology teaching are described, including implementation plan for the Academic Tutor System, implementation process for the Academic Tutor System and practical case analysis. Based on the findings of this study, it is concluded that the application of the Academic Tutor System benefits students' academic performance, enhances their research capabilities, and improves their overall comprehensive qualities. The vast majority of students support the implementation of the Academic Tutor System.
{"title":"Practice and exploration of implementing the \"academic tutor system\" in medical immunology.","authors":"Jiawen Lyu, Guangming Gong, Long Feng","doi":"10.1111/imcb.70075","DOIUrl":"10.1111/imcb.70075","url":null,"abstract":"<p><p>This study, from the perspective of a Medical Immunology student, sought to explore and investigate the implementation of the Academic Tutor System in the teaching of Medical Immunology. The characteristics and challenges of studying Medical Immunology, as well as the limitations of conventional teaching models in this discipline, are analyzed. Additionally, the concept and theory of the Academic Tutor System and its application in the learning process of medical students are introduced in this study. Moreover, the specific implementation methods of the Academic Tutor System in Medical Immunology teaching are described, including implementation plan for the Academic Tutor System, implementation process for the Academic Tutor System and practical case analysis. Based on the findings of this study, it is concluded that the application of the Academic Tutor System benefits students' academic performance, enhances their research capabilities, and improves their overall comprehensive qualities. The vast majority of students support the implementation of the Academic Tutor System.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"125-138"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}