title: Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies.
abstract: Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.
authors.affiliation: Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Nie
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.forename: Gewei
authors.initials: G
authors.lastname: Lian
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Yin
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Qu
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Ding
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000939:Epitopes; D005260:Female; D006801:Humans; D007114:Immunization; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011817:Rabbits; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus