Broad beta-CoV immunity and transmission blockade by a single-dose live-attenuated vaccine with atypical codon usage
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Nigeer Te
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Alex Wing Hong Chin
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Haogao Gu
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Janice Zhirong Jia
HKU-Pasteur Research Pole, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Yi Huang
Hubei Cancer Hospital Wuhan China
Samuel Mo Sheung Cheng
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Chee Wah Tan
Programme in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Jincun Zhao
Guangzhou National Laboratory
Kenrie Pui Yan Hui
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Michael Chi Wai Chan
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
Bo Feng
Ahmed Abdul Quadeer
Department of Electrical and Electronic Engineering, University of Melbourne
Matthew R. McKay
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Linfa Wang
Programme in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Sophie A. Valkenburg
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Malik Peiris
HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region
Leo Lit Man Poon
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region