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Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non\u2010hospitalized SARS\u2010CoV\u20102\u2010infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti\u2010spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti\u2010spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT\u2010PCR confirmed, non\u2010hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti\u2010spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS\u2010CoV\u20102 infection.<\/jats:p>","DOI":"10.1111\/imm.13349","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T11:04:06Z","timestamp":1619867046000},"page":"135-147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Development of a high\u2010sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS\u2010CoV\u20102 spike glycoprotein in serum and saliva"],"prefix":"10.1111","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-5569","authenticated-orcid":false,"given":"Sian E.","family":"Faustini","sequence":"first","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian 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