B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein.
Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunopathology.
Zhong
Xiaofen
X
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Yang
Huanghao
H
Guo
Zu-Feng
ZF
Sin
Wan-Yee Fion
WY
Chen
Wei
W
Xu
Junjie
J
Fu
Ling
L
Wu
Jie
J
Mak
Chun-Kit Gannon
CK
Cheng
Chak-Sum Samuel
CS
Yang
Yanzhen
Y
Cao
Shuyong
S
Wong
Tin-Yau
TY
Lai
Sik-To
ST
Xie
Yong
Y
Guo
Zhihong
Z
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000086462:Coronavirus Nucleocapsid Proteins; D018604:Epitope Mapping; D006723:Hong Kong; D006801:Humans; D016056:Immunodominant Epitopes; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins / Q000276:immunology; D019151:Peptide Library; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology*; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins / Q000276:immunology; D000086082:Viroporin Proteins
C487105:3a protein, SARS-CoV; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000086462:Coronavirus Nucleocapsid Proteins; D016056:Immunodominant Epitopes; D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D019151:Peptide Library; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D000086082:Viroporin Proteins; C087633:nonstructural protein, coronavirus; C578557:spike glycoprotein, SARS-CoV
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