Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity

Buchholz, Ursula J.; Bukreyev, Alexander; Yang, Lijuan; Lamirande, Elaine W.; Murphy, Brian R.; Subbarao, Kanta; Collins, Peter L.

doi:10.1073/pnas.0403492101

Cited by 396 publications

(414 citation statements)

References 32 publications

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“…A DNA vaccine encoding the S protein alone induces T-cell and neutralizing antibody responses and protected mice from SARSCoV infection (34), suggesting that the S protein is indeed the primary target for viral neutralization in SARS-CoV infection. This finding was also confirmed by at least four independent studies that use a carrier virus to express S in mice or primates (2,5,6,11). These reports highlight the potential for developing peptide-based vaccine candidates if neutralizing epitopes of S could be identified.…”

supporting

confidence: 62%

“…The S protein belongs to the class 1 viral fusion proteins and contains two heptad repeat domains (HR1 and HR2) in S2 or the C-terminal region. These two domains interact and play a crucial role in mediating virus-cell membrane fusion and entry of virus into cells.The S protein of CoV is known to be responsible for inducing host immune responses and virus neutralization by antibodies (5,7,14,25). For SARS-CoV, it has been demonstrated that prior infection provided protective immunity in a mouse model and that the passive transfer of neutralizing antibodies to naive mice also protected them from infection (26).…”

mentioning

confidence: 99%

“…The S protein of CoV is known to be responsible for inducing host immune responses and virus neutralization by antibodies (5,7,14,25). For SARS-CoV, it has been demonstrated that prior infection provided protective immunity in a mouse model and that the passive transfer of neutralizing antibodies to naive mice also protected them from infection (26).…”

mentioning

confidence: 99%

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Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

Keng

Zhang

Shen

et al. 2005

J Virol

103

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The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral entry into host cells; hence it is recognized as the primary target of neutralizing antibodies, and therefore knowledge of antigenic determinants that can elicit neutralizing antibodies could be beneficial for the development of a protective vaccine. Here, we expressed five different fragments of S, covering the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase fusion proteins in Escherichia coli and used the purified proteins to raise antibodies in rabbits. By Western blot analysis and immunoprecipitation experiments, we showed that all the antibodies are specific and highly sensitive to both the native and denatured forms of the full-length S protein expressed in virus-infected cells and transfected cells, respectively. Indirect immunofluorescence performed on fixed but unpermeabilized cells showed that these antibodies can recognize the mature form of S on the cell surface. All the antibodies were also able to detect the maturation of the 200-kDa form of S to the 210-kDa form by pulse-chase experiments. When the antibodies were tested for their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found that the anti-S⌬10 antibody, which was targeted to amino acid residues 1029 to 1192 of S, which include heptad repeat 2, has strong neutralizing activities, suggesting that this region of S carries neutralizing epitopes and is very important for virus entry into cells.A novel coronavirus (CoV) was identified as the etiological agent of severe acute respiratory syndrome (SARS) (8,9,15,20). CoVs are positive-strand RNA viruses, and the virion consists of a nucleocapsid (N) core surrounded by an envelope containing three membrane proteins, spike (S), membrane (M), and envelope (E), that are common to all members of the genus (for reviews, see references 16 and 24). The S protein, which forms morphologically characteristic projections on the virion surface, binds to host receptors and mediates membrane fusion. The M and E proteins are important for viral particle assembly, while N is important for viral RNA packaging.The S protein of CoV is a type 1 integral membrane glycoprotein. It is cotranslationally glycosylated and oligomerized at the endoplasmic reticulum. Its N-linked high-mannose side chains are trimmed and modified and become endoglycosidase H (EndoH) resistant during the transportation to the Golgi apparatus. For some but not all CoVs, the S protein is cleaved into the N-terminal S1 and C-terminal S2 subunits, which contain receptor binding and membrane fusion domains (10, 32), respectively. The mature forms of S are assembled into virions, which release from infected cells. A portion of S is transported to the plasma membrane, resulting in cell-cell fusion or formation of syncytia. The S protein belongs to the class 1 viral fusion proteins and contains two heptad repeat domains (HR1 and HR2) in S2 or the C-...

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supporting

confidence: 62%

mentioning

confidence: 99%

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Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

Keng

Zhang

Shen

et al. 2005

J Virol

103

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“…Several experimental vaccines have been developed and tested in a murine viral replication model (8)(9)(10). These studies showed that S-based vaccines protected against SARS-CoV challenge in this animal model.…”

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confidence: 99%

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Yang

Werner

Kong

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

249

284

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Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.angiotensin-converting enzyme 2 ͉ enhancement ͉ immunoglobulin G ͉ pseudovirus

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“…Furthermore, incomplete inactivation can leave residual infectivity in such vaccines, posing further risk to vaccinees (9,10). The SARS-CoV spike S glycoprotein is the viral neutralization and major protective antigen (11). Full-length or fragments of recombinant purified S have been shown to be immunogenic in small-animal models, but their safety and efficacy have not yet been evaluated in primates.…”

mentioning

confidence: 99%

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

DiNapoli

Kotelkin

Yang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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130

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Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity

Cited by 396 publications

References 32 publications

Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

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