Broad beta-Coy immunity and transmission blockade by a single-dose live-attenuated vaccine with atypical codon usage

• 成果类型: Article
• 署名作者: Te, Nigeer; Chin, Alex Wing Hong; Gu, Haogao; Jia, Janice Zhirong; Huang, Yi; Cheng, Samuel Mo Sheung; Tan, Chee Wah; Zhao, Jincun; Hui, Kenrie Pui Yan; Chan, Michael Chi Wai; Feng, Bo; Quadeer, Ahmed Abdul; Mckay, Matthew R.; Wang, Linfa; Valkenburg, Sophie A.; Peiris, Malik; Poon, Leo Lit Man
• 署名单位: University of Hong Kong; University of Hong Kong; HKU Pasteur Research Pole; National University of Singapore; National University of Singapore; State Key Laboratory of Respiratory Disease; Guangzhou Medical University; Guangzhou Laboratory; Chinese University of Hong Kong; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; CUHK Shenzhen Research Institute; The Chinese University of Hong Kong, Shenzhen; University of Melbourne; University of Melbourne; Peter Doherty Institute; University of Hong Kong
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2518645123
• 发表日期: 2026-01-27
• 页码: e2518645123
• 关键词: coronavirus; vaccine; codon; live-attenuated virus; SARS-COV-2 OMICRON; influenza-virus; pair; PROTECTION; cd4(+); BIAS; cell

摘要

Current COVID-19 vaccines have saved countless lives but primarily aim to induce immunity to the spike or its RBD protein and often fail to confer broad or durable protection against rapidly evolving variants and prevent transmission. Here, we invented a live-attenuated broad-spectrum coronavirus vaccine (cb1) by changing the codon usage bias of SARS-CoV-2 genome, which maintained amino acid conservation but reduced virulence. A single intranasal dose of cb1 vaccine elicits remarkably broad and potent immunity that overcomes existing parenteral vaccine's limitations. cb1 induced robust neutralizing antibody and T cell responses that translated into complete protection in animal models, including prevention of viral transmission to unvaccinated contacts. Notably, cb1 provided cross-protection not only against diverse SARS-CoV-2 variants of concern but also against more divergent SARS-CoV-1 and hCoV-OC43, a breadth of immunity unparalleled by current vaccines. These findings highlight the potential of cb1 to address urgent needs for next-generation COVID-19 vaccines that elicit mucosal immunity with broad, long-lasting efficacy, eliminating the necessity for frequent updates.