Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein.

Abstract

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a protective Ag for vaccine design. We previously demonstrated that the receptor-binding domain (RBD) of S protein contains multiple conformational epitopes (Conf I-VI) that confer the major target of neutralizing Abs. Here we show that the recombinant RBDs derived from the S protein sequences of Tor2, GD03, and SZ3, the representative strains of human 2002-2003 and 2003-2004 SARS-CoV and palm civet SARS-CoV, respectively, induce in the immunized mice and rabbits high titers of cross-neutralizing Abs against pseudoviruses expressing S proteins of Tor2, GD03, and SZ3. We also demonstrate that the Tor2-RBD induced-Conf I-VI mAbs can potently neutralize both human SARS-CoV strains, Tor2 and GD03. However, only the Conf IV-VI, but not Conf I-III mAbs, neutralize civet SARS-CoV strain SZ3. All these mAbs reacted significantly with each of the three RBD variants (Tor2-RBD, GD03-RBD, and SZ3-RBD) that differ at several amino acids. Regardless, the Conf I-IV and VI epitopes were completely disrupted by single-point mutation of the conserved residues in the RBD (e.g., D429A, R441A, or D454A) and the Conf III epitope was significantly affected by E452A or D463A substitution. Interestingly, the Conf V epitope, which may overlap the receptor-binding motif and induce most potent neutralizing Abs, was conserved in these mutants. These data suggest that the major neutralizing epitopes of SARS-CoV have been apparently maintained during cross-species transmission, and that RBD-based vaccines may induce broad protection against both human and animal SARS-CoV variants.

• Authors: Yuxian He, Jingjing Li, Wenhui Li, Sara Lustigman, Michael Farzan, Shibo Jiang
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 10 Pg. 6085-92 (May 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16670317 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Viral
• Membrane Glycoproteins
• Receptors, Virus
• Spike Glycoprotein, Coronavirus
• Viral Envelope Proteins
• spike glycoprotein, SARS-CoV
• spike protein, mouse hepatitis virus

Topics

• Animals
• Antibodies, Monoclonal (metabolism)
• Antibodies, Viral (metabolism)
• Binding Sites, Antibody
• Cross Reactions
• Female
• Humans
• Membrane Glycoproteins (genetics, immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Neutralization Tests
• Protein Structure, Tertiary (genetics)
• Rabbits
• Receptors, Virus (metabolism)
• Severe acute respiratory syndrome-related coronavirus (immunology, metabolism)
• Spike Glycoprotein, Coronavirus
• Viral Envelope Proteins (genetics, immunology, metabolism)
• Viverridae (virology)