Quantifying post-vaccination protective anti-SARS-CoV-2 IgG antibodies in blood and saliva with a fully automated, high throughput digital immunoassay
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Abstract
Background
Antibodies induced by COVID-19 vaccination have been shown to wane over time. Current tests for assessing virus-neutralizing antibodies are complex and time-intensive. There is a need for a simple diagnostic test that measures levels of protective antibodies to help monitor immunity status.
Method
Using a commercially available FDA-authorized semi-quantitative SARS-CoV-2 IgG test, we monitored the duration of the immune response in dried blood microsamples (DBS) and saliva to vaccination by 3 different vaccines across prospective cohorts of 8 COVID-19 naïve and 29 COVID-19 recovered individuals over a six-month period. We correlated the results to a binding blockade assay validated to a live virus neutralization assay to validate the test for measurement of protective antibodies.
Results
The immune response characteristics between the two mRNA vaccines were similar over the 6-month period in both the COVID-19 naïve and recovered cohorts. IgG titers in DBS were generally 3-4 orders of magnitude higher than in saliva, and longitudinal profiles were highly correlated between the two matrices (R m = 0.80). Median IgG concentrations post-vaccination declined to <10% neutralization capacity with all vaccines by six months.
Conclusions
The potential of a simple, fully automated high throughput anti-SARS-CoV-2 IgG test to quantitatively measure protective antibodies in samples collected remotely or at the point of care was demonstrated. The IgG immune response and protective immunity was shown to decline significantly by six months.
Plain Language Summary
In response to infection the immune system produces proteins called antibodies that recognize and bind to foreign invaders. Vaccines train the immune system to recognize and produce antibodies against specific invaders, such as SAR-CoV-2. Measurement of antibody levels in blood help monitor a person’s response to vaccination and have been shown to correlate with protection against disease, which wanes over time following vaccination. It is desirable to have an easy test that predicts protection against infection and measuring antibody levels may provide a solution, however different tests report results differently hindering the establishment of a cutoff for protected vs. not. We quantified antibody levels in saliva and dried blood microsamples (DBS) following vaccination using an automated semi-quantitative IgG test. By reporting concentration of antibodies, and if anchored to an international standard, this test could help establish a cutoff of protection that would be transferable across the multiple different test types. Furthermore, by measuring in saliva and DBS we demonstrate an easy path to at-home or point-of-care sample collection, which could allow wide-scale monitoring of immune protection against SARS-CoV-2.
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SciScore for 10.1101/2022.01.21.22269165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Sample collection and preparation: This study was IRB approved (Advarra) and all participants provided written informed consent.
Field Sample Permit: Study Cohorts: Matching saliva and DBS were collected from 13 donors pre- and post-vaccination out to 6 months, with frequent sampling during weeks one and two; an additional 2 donors donated only saliva (cohort 1).Sex as a biological variable not detected. Randomization not detected. Blinding Samples were blinded before testing. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Details of the technology and instrument are given elsewhere.12,13 Anti-SARS-CoV-2 IgG assay and research protocol: Anti-SARS-CoV-2 IgG … SciScore for 10.1101/2022.01.21.22269165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Sample collection and preparation: This study was IRB approved (Advarra) and all participants provided written informed consent.
Field Sample Permit: Study Cohorts: Matching saliva and DBS were collected from 13 donors pre- and post-vaccination out to 6 months, with frequent sampling during weeks one and two; an additional 2 donors donated only saliva (cohort 1).Sex as a biological variable not detected. Randomization not detected. Blinding Samples were blinded before testing. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Details of the technology and instrument are given elsewhere.12,13 Anti-SARS-CoV-2 IgG assay and research protocol: Anti-SARS-CoV-2 IgG measurements were made with the Simoa® Semi-Quantitative SARS-CoV-2 IgG Antibody Test. Anti-SARS-CoV-2 IgGsuggested: NoneBiotinylated anti-human IgG detector antibodies are then mixed with the capture beads, and the detector antibodies bind to the captured sample IgG. anti-human IgGsuggested: NoneThis is a chimeric monoclonal antibody combining the constant domains of the human IgG1 molecule with mouse variable regions. human IgG1suggested: NoneSoftware and Algorithms Sentences Resources Statistical Analysis: Statistical analyses were performed using Graphpad prism (version 8.4.0 (671) Graphpadsuggested: (GraphPad, RRID:SCR_000306), Microsoft Excel (16.0.13530.20132), or R studio, R v.4.0.3 (package rmcorr). Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Decay curves of IgG levels were fit with one-phase exponential decays in Graphpad Prism (Fig 4e and Supplementary Figure S2) of the form: Y=(Y0 - Plateau)*exp(-K*X) + Plateau. Graphpad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has certain limitations, the foremost being we examined only humoral (antibody-mediated) and not cellular-immunity; we hoped to provide initial support of the use of anti-spike IgG concentration as a correlate of protection for vaccine efficacy. Additional limitations include a small sample size of 37 donors total, and 13 donors used for saliva / DBS high-frequency temporal sampling. Conclusions about the kinetics of IgG increase and decrease were limited by our sampling frequency, which could not be done more frequently due to declining willingness of donors to provide finger-stick blood. Challenges with vaccine access, combined with vaccine hesitancy in some communities continue to present barriers to achievement of herd immunity. When combined with a growing appreciation for limitations in durability of COVID-19 vaccine-induced immune response, an accurate understanding of population-based immunity becomes a critical input to inform public health policy including national vaccination programs, mask mandates, social distancing, and potentially more severe restrictions on mobility within or between communities. The work presented here establishes a potential pathway for non-invasive, broadly accessible collection of samples suitable for high-throughput quantitative serological testing to aid in defining SARS-CoV-2 immunity at population scale.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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