Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults.

Autor: Thomas AC; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. amyc.thomas@bristol.ac.uk.; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK. amyc.thomas@bristol.ac.uk., Oliver E; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Baum HE; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Gupta K; School of Biochemistry, University of Bristol, Bristol, UK.; BrisSynBio, University of Bristol, Bristol, UK.; Imophoron Ltd, Science Creates, Old Market, Midland Road, Bristol, UK., Shelley KL; School of Biochemistry, University of Bristol, Bristol, UK.; BrisSynBio, University of Bristol, Bristol, UK.; School of Chemistry, University of Bristol, Bristol, UK., Long AE; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Jones HE; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Smith J; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Hitchings B; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., di Bartolo N; School of Biochemistry, University of Bristol, Bristol, UK.; NIHR Blood and Transplant Research Unit in Red Cell Products, University of Bristol, Bristol, UK., Vasileiou K; School of Biochemistry, University of Bristol, Bristol, UK., Rabi F; School of Biochemistry, University of Bristol, Bristol, UK., Alamir H; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Eghleilib M; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Francis O; Bristol Veterinary School, University of Bristol, Bristol, UK., Oliver J; Bristol Vaccine Centre, Population Health Sciences, University of Bristol, Bristol, UK., Morales-Aza B; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Obst U; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Shattock D; Bristol Bioresource Laboratories, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Barr R; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.; Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, Upper Maudlin Street, Bristol, BS2 8BJ, UK., Collingwood L; Bristol Vaccine Centre, Population Health Sciences, University of Bristol, Bristol, UK., Duale K; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Grace N; Bristol Vaccine Centre, Population Health Sciences, University of Bristol, Bristol, UK., Livera GG; Bristol Vaccine Centre, Population Health Sciences, University of Bristol, Bristol, UK., Bishop L; Bristol Vaccine Centre, Population Health Sciences, University of Bristol, Bristol, UK., Downing H; NIHR Bristol Biomedical Research Centre, University of Bristol, Bristol, UK., Rodrigues F; Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.; Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal., Timpson N; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK., Relton CL; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK., Toye A; School of Biochemistry, University of Bristol, Bristol, UK.; NIHR Blood and Transplant Research Unit in Red Cell Products, University of Bristol, Bristol, UK., Woolfson DN; School of Biochemistry, University of Bristol, Bristol, UK.; BrisSynBio, University of Bristol, Bristol, UK.; School of Chemistry, University of Bristol, Bristol, UK., Berger I; Max Planck Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK., Goenka A; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.; Paediatric Immunology & Infectious Diseases, Bristol Royal Hospital for Children, Bristol, UK., Davidson AD; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Gillespie KM; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Williams AJK; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Bailey M; Bristol Veterinary School, University of Bristol, Bristol, UK., Brooks-Pollock E; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Finn A; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.; Paediatric Immunology & Infectious Diseases, Bristol Royal Hospital for Children, Bristol, UK., Halliday A; Bristol Vaccine Centre, School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2023 Mar 15; Vol. 3 (1), pp. 37. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1038/s43856-023-00264-2
Abstrakt: Background: Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance.
Methods: We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses. The best-performing assays were field-tested in 20 household outbreaks.
Results: We demonstrate in test accuracy (N = 320), spike IgG (ROC AUC: 95.0%, 92.8-97.3%) and spike IgA (ROC AUC: 89.9%, 86.5-93.2%) assays to discriminate best between pre-pandemic and post COVID-19 saliva samples. Specificity was 100% in younger age groups (0-19 years) for spike IgA and IgG. However, sensitivity was low for the best-performing assay (spike IgG: 50.6%, 39.8-61.4%). Using machine learning, diagnostic performance was improved when a combination of tests was used. As expected, salivary IgA was poorly correlated with serum, indicating an oral mucosal response whereas salivary IgG responses were predictive of those in serum. When deployed to household outbreaks, antibody responses were heterogeneous but remained a reliable indicator of recent infection. Intriguingly, unvaccinated children without confirmed infection showed evidence of exposure almost exclusively through specific IgA responses.
Conclusions: Through robust standardisation, evaluation and field-testing, this work provides a platform for further studies investigating SARS-CoV-2 transmission and mucosal immunity with the potential for expanding salivo-surveillance to other respiratory infections in hard-to-reach settings.
(© 2023. The Author(s).)
Databáze: MEDLINE