Article Impact Level: HIGH Data Quality: STRONG Summary of Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.2518645123 Dr. Nigeer Te et al.
Points
- The novel cb1 vaccine utilizes a rational codon deoptimization strategy to weaken the SARS-CoV-2 virus without altering its amino acid sequence to provide broad spectrum immunity against diverse beta coronavirus strains.
- Animal studies demonstrated that a single intranasal administration of the vaccine provided complete protection against lethal challenges from ancestral SARS-CoV-2 as well as the more recent Omicron EG.5 variants.
- Preclinical trials in hamster models showed that the cb1 vaccine effectively blocked the transmission of the virus through aerosols and droplets and direct contact which current parenteral vaccines often fail to achieve.
- When utilized as a heterologous booster the cb1 candidate successfully updated existing immunity and broadened the antibody response to overcome the challenges of immune imprinting from previous mRNA or inactivated vaccinations.
- This live attenuated platform offers a promising strategy for future pandemic preparedness by inducing potent mucosal and systemic responses that could eliminate the need for frequent strain specific vaccine updates globally.
Summary
Researchers at HKUMed have developed cb1, a live-attenuated vaccine candidate designed to provide broad-spectrum protection against beta-coronaviruses through a rational codon-deoptimization strategy. While current parenteral vaccines saved approximately 20 million lives in their first year, their efficacy against transmission and emerging Omicron subvariants has significantly diminished due to narrow spike-protein targeting. By altering the codon usage bias of the SARS-CoV-2 genome, the cb1 platform reduces virulence without modifying the viral amino acid sequence, enabling a safe intranasal administration that exposes the host to a comprehensive array of antigens.
In preclinical animal models, a single intranasal dose of cb1 elicited robust neutralizing antibody (nAb) and T-cell responses in both systemic and mucosal tissues. The vaccine provided complete protection in mice against lethal challenges from ancestral SARS-CoV-2, Omicron subvariants EG.5 and JN.1, and divergent strains such as SARS-CoV-1 and hCoV-OC43. Notably, cb1 achieved a 100% blockade of viral transmission in hamster models, successfully neutralizing spread via aerosols, droplets, and direct contact—addressing a critical clinical gap in existing intramuscular vaccine regimes.
Furthermore, cb1 effectively served as a heterologous booster in animals previously immunized with mRNA or inactivated vaccines, broadening the antibody response to overcome established immune imprinting. This mucosal approach suggests that a single-dose platform could eliminate the necessity for frequent strain-specific updates while providing a robust defense against potential zoonotic spillovers from novel sarbecoviruses. These findings highlight the potential of codon-deoptimized vaccines as a game-changing tool for long-term pandemic preparedness and community-level transmission control.
Link to the article: https://www.pnas.org/doi/10.1073/pnas.2518645123
References
Te, N., Chin, A. W. H., Gu, H., Zhirong Jia, J., Huang, Y., Cheng, S. M. S., Wah Tan, C., Zhao, J., Pui Yan Hui, K., Chi Wai Chan, M., Feng, B., Abdul Quadeer, A., McKay, M. R., Wang, L., Valkenburg, S. A., Peiris, M., & Lit Man Poon, L. (2026). Broad beta-CoV immunity and transmission blockade by a single-dose live-attenuated vaccine with atypical codon usage. Proceedings of the National Academy of Sciences, 123(4), e2518645123. https://doi.org/10.1073/pnas.2518645123
