SARS vaccine development

Abstract

Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.

Figure 1

Strategy for designing vaccines for severe acute respiratory syndrome (SARS) using inactivated SARS-associated coronavirus. This virus expresses several structural proteins, including nucleocapsid (N), membrane (M), envelope (E), and spike (S).

Figure 2

Strategies for designing vaccines for severe acute respiratory syndrome (SARS) using A) spike (S) protein and B) fragments containing neutralizing epitopes. SP, signal peptide; RBD, receptor binding domain; FP, fusion peptide; HR, heptad repeat; TM, transmembrane domain; CP, cytoplasm domain. IDS, immunodominant sites I to V corresponding to the sequences of amino acid residues 9–71, 171–224, 271–318, 528–635, and 842–913, respectively. The residue numbers of each region correspond to their positions in the S protein of SARS–associated coronavirus (SARS-CoV) strain Tor2. RBD contains the major neutralizing epitopes in the S protein. The recombinant RBD may be used as an efficacious and safe vaccine for preventing infection by SARS-CoV strains with distinct genotypes.