Development and Characterization of a Severe Acute Respiratory Syndrome–Associated Coronavirus–Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice

Greenough, Thomas C.; Babcock, Gregory J.; Roberts, Anjeanette; Hernández, Héctor J.; Thomas, William D.; Coccia, Jennifer A.; Graziano, Robert F.; Srinivasan, M. S.; Lowy, Israel; Finberg, Robert W.; Subbarao, Kanta; Vogel, Leatrice; Somasundaran, Mohan; Luzuriaga, Katherine; Sullivan, John L.; Ambrosino, Donna M.

doi:10.1086/427242

Cited by 149 publications

(184 citation statements)

References 23 publications

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“…However, there is no direct evidence that patients with SARS had previous exposure to a related virus. Also, macrophages are not productively infected by SARS-CoV, and there was no evidence of enhanced disease in animals that were infected with SARS-CoV following passive transfer of antibodies against SARSCoV induced by infection or immunization (68, [141][142][143][144].…”

Section: Humoral Immune Response To Sars-cov Infectionmentioning

confidence: 99%

The Immunobiology of SARS

Chen

Subbarao

2007

Annu. Rev. Immunol.

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258

276

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Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models.

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Section: Humoral Immune Response To Sars-cov Infectionmentioning

confidence: 99%

The Immunobiology of SARS

Chen

Subbarao

2007

Annu. Rev. Immunol.

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258

276

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“…The main receptor for SARS-CoV is angiotensin-converting enzyme 2 (ACE2) [7], and it has been shown that amino acids 318-510 of the SARS-CoV S protein are sufficient to bind to ACE2 [8,9]. The S protein is an attractive target for both therapeutics and vaccine development because monoclonal antibodies to the S protein can neutralize SARS-CoV infection [10,11]. Moreover, the S protein has been shown to induce serum neutralizing antibodies and confer protective immunity against SARS-CoV challenge [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: Implications for a subunit vaccine

Zakhartchouk

Sharon

Satkunarajah

et al. 2007

Vaccine

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We studied the immunogenicity of an anti-SARS subunit vaccine comprised of the fragment of the SARS coronavirus (SARS-CoV) spike protein amino acids 318-510 (S318-510) containing the receptor-binding domain. The S protein fragment was purified from the culture supernatant of stably transformed HEK293T cells secreting a tagged version of the protein. The vaccine was given subcutaneously to 129S6/SvEv mice in saline, with alum adjuvant or with alum plus CpG oligodeoxynucleotides (ODN). Mice immunized with the adjuvanted antigen elicited strong antibody and cellular immune responses; furthermore, adding the CpG ODN to the alum resulted in increased IgG2a antibody titers and a higher number of INF-gamma-secreting murine splenocytes. Mice vaccinated with S318-510 deglycosylated by PNGase F (dgS318-510) showed a lower neutralizing antibody response but had similar numbers of INF-gamma-producing cells in the spleen. This finding suggests that carbohydrate is important for the immunogenicity of the S318-510 protein fragment and provide useful information for designing an effective and safe SARS subunit vaccine.

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“…Several epitope sites, defined by polyclonal or monoclonal antibodies, have been identified on the S protein, depending on experimental conditions, all lying within wide or narrow regions between a.a. 12-1,192 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31.. Defining conserved immunodominant epitope regions of the S protein is of crucial importance for future anti-SARS vaccine development.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV Genome Polymorphism: A Bioinformatics Study

Pavlović-Lažetić¹,

Mitić²,

Tomović³

et al. 2005

Genomics, Proteomics &Amp; Bioinformatics

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A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a “profile”, were determined and discussed ("profile" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.

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Development and Characterization of a Severe Acute Respiratory Syndrome–Associated Coronavirus–Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice

Abstract: Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.

Cited by 149 publications

References 23 publications

The Immunobiology of SARS

The Immunobiology of SARS

Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: Implications for a subunit vaccine

SARS-CoV Genome Polymorphism: A Bioinformatics Study

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