Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies.
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Fenwick C
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Croxatto A
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Coste AT
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Pojer F
Protein Production and Structure Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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André C
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Pellaton C
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Farina A
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Campos J
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Hacker D
Protein Production and Structure Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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Lau K
Protein Production and Structure Core Facility, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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Bosch BJ
Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
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Gonseth Nussle S
Centre for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
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Bochud M
Centre for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
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D'Acremont V
Centre for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
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Trono D
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
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Greub G
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland giuseppe.pantaleo@chuv.ch gilbert.greub@chuv.ch.
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Pantaleo G
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland giuseppe.pantaleo@chuv.ch gilbert.greub@chuv.ch.
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Published in:
- Journal of virology. - 2020
English
SARS-CoV-2-specific antibody responses to the Spike (S) protein monomer, S protein native trimeric form or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection (n=93) and in individuals enrolled in a post-infection seroprevalence population study (n=578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein and a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute infection phase samples. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection cohort. Seroprevalence in a 'positive patient contacts' group (n=177) was underestimated by N protein assays by 10.9 to 32.2% and the 'random selected' general population group (n=311) was reduced up to 45% reduction relative to S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and post-infection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection but that responses against N appear to wane in the post-infection phase while those against S protein persist over time. The most sensitive serological assay in both acute and post-infection phases used the native S protein trimer as binding antigen that has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe that these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.
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hybrid
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https://sonar.ch/global/documents/278247
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