Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice

Bisht, Himani; Roberts, Anjeanette; Vogel, Leatrice; Bukreyev, Alexander; Collins, Peter L.; Murphy, Brian R.; Subbarao, Kanta; Moss, Bernard

doi:10.1073/pnas.0401939101

Cited by 403 publications

(469 citation statements)

References 32 publications

(36 reference statements)

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“…Immune protection against SARS-CoV infection has been conferred by vaccination directed toward the S glycoprotein (8,9), and this effect is mediated by humoral immunity. The evolving molecular heterogeneity of SARS-CoV (11,12,21,22) has raised concerns about the breadth and efficacy of protection with specific vaccine strains and the possible development of immune escape.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Yang

Werner

Kong

et al. 2005

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

251

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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Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

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.

251

284

View full text Add to dashboard Cite

show abstract

“…Although SARSCoV infection of humans has been contained through effective infection-control measures, resurgence is still a threat due to the presence of animal reservoirs (12). Consequently, several vaccines have been urgently developed (21)(22)(23). Studies of the immune response to coronaviruses suggest that both humoral and cellular immunity contribute to protection (61)(62)(63)(64).…”

Section: Discussionmentioning

confidence: 99%

“…However, due to the lack of identified SARS-CoV-specific CTL epitopes, the role of CTLs in immunopathogenesis and their function in viral clearance remain unclear. In addition, with the recent development of several vaccines against SARS-CoV, there is currently a need for a reliable markers to indicate effective SARS-CoV T cell responses (21)(22)(23). Hence, the identification of specific CTL epitopes should be of great use for both understanding viral control mechanisms and SARS vaccine evaluation.…”

mentioning

confidence: 99%

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

Zhou

De-sheng

et al. 2006

The Journal of Immunology

107

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Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-γ ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2+ SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411–420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-γ-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.

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“…A recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV S protein was protective in mice (14) but has not been tested in primates, and the safety of VSV in humans remains to be established. Recombinant modified vaccinia Ankara (MVA) virus expressing SARS-CoV S protein was immunogenic and protective in rodent and primate models (15)(16)(17); however, one group found that the MVA/SARSCoV S-immunized ferrets developed hepatitis upon challenge with SARS-CoV (17). Vaccine constructs based on replication defective human adenovirus type 5 expressing a partial or full-length SARSCoV S protein have been evaluated for immunogenicity in rats and monkeys (18,19), but immunization depends on a high vaccine dose, and safety and protective efficacy remain to be demonstrated.…”

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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158

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Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice

Cited by 403 publications

References 32 publications

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

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

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