Saliva-Based ELISAs for Effective SARS-CoV-2 Antibody Monitoring in Vaccinated Individuals

Casian, Joseph G.; Angel, Aaron N.; Lopez, Ronell; Bagos, Cedie; MacMullan, Melanie A.; Bui, Mindy L; Chellamathu, Prithivi; Das, Sudipta Sekhar; Turner, Fred; Slepnev, Vladimir I.; Ibrayeva, Albina

doi:10.3389/fimmu.2021.701411

Cited by 9 publications

(9 citation statements)

References 18 publications

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“…Only a handful of prior studies have assessed the presence of salivary anti-SARS-CoV-2 antibodies in naturally infected 15 , 17 , 18 , 33 , 34 or vaccinated individuals 35 , 36 , but have presented differing results, and have universally acknowledged challenges with measurement of salivary antibodies and a need for improvement of salivary assays. Faustini et al detected anti-spike SARS-CoV-2 antibodies in the serum of 95% of previously infected patients, but salivary antibodies were detected in only 17.5% of this cohort, primarily in those with higher serum antibody levels 18 .…”

Section: Discussionmentioning

confidence: 99%

Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity

Thomas

Karger

Altawallbeh

et al. 2022

Sci Rep

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We assessed the feasibility of a highly sensitive immunoassay method based on single molecule array (Simoa) technology to detect IgG and IgA antibodies against SARS-CoV-2 spike protein receptor binding domain (RBD) in saliva from individuals with natural or vaccine-induced COVID-19 immunity. The performance of the method was compared to a laboratory-developed SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay (ELISA). Paired serum and saliva specimens were collected from individuals (n = 40) prior to and 2 weeks after receiving an initial prime COVID-19 vaccine dose (Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273). Saliva was collected using a commercially available collection device (OraSure Inc.) and SARS-CoV-2 RBD IgG antibodies were measured by an indirect ELISA using concentrated saliva samples and a Simoa immunoassay using unconcentrated saliva samples. The IgG results were compared with paired serum specimens that were analyzed for total RBD antibodies using the ELISA method. The analytical sensitivity of the saliva-based Simoa immunoassay was five orders of magnitude higher than the ELISA assay: 0.24 pg/mL compared to 15 ng/mL. The diagnostic sensitivity of the saliva ELISA method was 90% (95% CI 76.3–97.2%) compared to 91.7% (95% CI 77.5–98.2%) for the Simoa immunoassay without total IgG-normalization and 100% (95% CI 90.3–100%) for the Simoa immunoassay after total IgG-normalization when compared to the serum ELISA assay. When analyzed using the SARS-CoV-2 RBD IgG antibody ELISA, the average relative increase in antibody index (AI) between the saliva of the post- and pre-vaccinated individuals was 8.7 (AIpost/pre). An average relative increase of 431 pg/mL was observed when the unconcentrated saliva specimens were analyzed using the Simoa immunoassay (SARS-CoV-2 RBD IgGpost/pre). These findings support the suitability of concentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG antibodies via ELISA, and unconcentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG and IgA using an ultrasensitive Simoa immunoassay.

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Section: Discussionmentioning

confidence: 99%

Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity

Thomas

Karger

Altawallbeh

et al. 2022

Sci Rep

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“…SARS-CoV-2 immunity in the respiratory mucosa, particularly in saliva, includes locally secreted dimeric IgA as well as IgG that comes largely from the systemic immune response via gingival transduction in the gums ( 15 ). Correlating IgG plasma and saliva levels from recovered COVID-19 patients have been reported to persist for at least 3 months ( 15 – 17 ). Our study provides evidence of long-term and constant SARS-CoV-2 RBD IgG levels for most COVID-19 convalescent individuals not only in plasma but - to our knowledge - for more than one year in saliva.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Antibodies Are Persisting in Saliva for More Than 15 Months After Infection and Become Strongly Boosted After Vaccination

Pinilla

Heinzel²,

Caminada³

et al. 2021

Front. Immunol.

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SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.

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“…Coronavirus disease 2019 (COVID-19) convalescent patients and vaccinated individuals produce both serum and mucosal antibodies (2,3). Although serum antibodies are traditionally measured, saliva sampling for mucosal antibody measurements has shown promising first results leading to the first FDA approved saliva based antibody test in June 2021 (4,5). As saliva sampling is quick and painless this could be a convenient alternative to serum sampling, in particular for children.…”

Section: Introductionmentioning

confidence: 99%

Differences in systemic and mucosal SARS-CoV-2 antibody prevalence in a prospective cohort of Dutch children

et al. 2022

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BackgroundAs SARS-CoV-2 will likely continue to circulate, low-impact methods become more relevant to monitor antibody-mediated immunity. Saliva sampling could provide a non-invasive method with reduced impact on children. Studies reporting on the differences between systemic and mucosal humoral immunity to SARS-CoV-2 are inconsistent in adults and scarce in children. These differences may be further unraveled by exploring associations to demographic and clinical variables.MethodsTo evaluate the use of saliva antibody assays, we performed a cross-sectional cohort study by collecting serum and saliva of 223 children attending medical services in the Netherlands (irrespective of SARS-CoV-2 exposure, symptoms or vaccination) from May to October 2021. With a Luminex and a Wantai assay, we measured prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid-specific IgG and IgA in serum and saliva and explored associations with demographic variables.FindingsThe S-specific IgG prevalence was higher in serum 39% (95% CI 32 – 45%) than in saliva 30% (95% CI 24 – 36%) (P ≤ 0.003). Twenty-seven percent (55/205) of children were S-specific IgG positive in serum and saliva, 12% (25/205) were only positive in serum and 3% (6/205) only in saliva. Vaccinated children showed a higher concordance between serum and saliva than infected children. Odds for saliva S-specific IgG positivity were higher in girls compared to boys (aOR 2.63, P = 0.012). Moreover, immunocompromised children showed lower odds for S- and RBD-specific IgG in both serum and saliva compared to healthy children (aOR 0.23 – 0.25, P ≤ 0.050).ConclusionsWe showed that saliva-based antibody assays can be useful for identifying SARS-CoV-2 humoral immunity in a non-invasive manner, and that IgG prevalence may be affected by sex and immunocompromisation. Differences between infection and vaccination, between sexes and between immunocompromised and healthy children should be further investigated and considered when choosing systemic or mucosal antibody measurement.

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Saliva-Based ELISAs for Effective SARS-CoV-2 Antibody Monitoring in Vaccinated Individuals

Cited by 9 publications

References 18 publications

Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity

Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity

SARS-CoV-2 Antibodies Are Persisting in Saliva for More Than 15 Months After Infection and Become Strongly Boosted After Vaccination

Differences in systemic and mucosal SARS-CoV-2 antibody prevalence in a prospective cohort of Dutch children

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