Iterative structure-based improvement of a respiratory syncytial virus fusion glycoprotein vaccine
By M. Joyce, Baoshan Zhang, Li Ou, Man Chen, Gwo-Yu Chuang, A. Druz, W. Kong, Y. Lai, E. J. Rundlet, Y. Tsybovsky and 15 more. 2016
142 citations recorded by the source corpus.
Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.
Subfields: Epidemiology, Infectious Diseases
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Citations in the corpus
- Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, methodology): “It is possible that second-generation prefusion RSV F antigens with improved stability and immunogenicity (Joyce et al., 2016) would yield even more potent responses when presented in multivalent form on I53-50 or other nanoparticles.”