Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study

Walmsley, Sharon; Szadkowski, Leah; Wouters, Bradly G.; Clarke, Rosemarie; Colwill, Karen; Rochon, Paula A.; Brudno, Michael; Ravindran, Rizani; Raboud, Janet; McGeer, Allison; Oza, Amit M.; Graham, Christopher; Silva, Amanda; Manase, Dorin; Parente, Laura; Simpson, Jacqueline; Dayam, Roya Monica; Pasculescu, Adrian; Gingras, Anne‐Claude

doi:10.1101/2022.02.09.22270734

Cited by 9 publications

(14 citation statements)

References 33 publications

(43 reference statements)

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“…36 Additionally, these assays are used in > 30 studies focused on infection and/or vaccine responses across different cohorts, e.g. in persons predicted to have a weaker immune response (based, for example, on age 37 or health conditions 38 ), or who are likely to be exposed to infection from the workplace. The results of the assays have critically helped informed public health decisions.…”

Section: Discussionmentioning

confidence: 99%

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

et al. 2022

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Objectives Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been instrumental in detecting previous exposures and analyzing vaccine‐elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS‐CoV‐2 antibodies, discriminate between natural infection‐ and vaccination‐induced responses, and assess antibody‐mediated inhibition of the spike‐angiotensin converting enzyme 2 (ACE2) interaction. Methods We developed methods and reagents to detect SARS‐CoV‐2 antibodies by enzyme‐linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2‐spike or ‐RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. Results Our single‐point IgG‐based ELISAs accurately distinguished non‐infected and infected individuals. For seroprevalence assessment (in a non‐vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti‐spike and ‐RBD (but not ‐N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. Conclusions Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike‐ACE2 interactions in high‐throughput enables large‐scale analyses of humoral immune responses to SARS‐CoV‐2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter‐laboratory data comparison and aggregation.

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Section: Discussionmentioning

confidence: 99%

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

et al. 2022

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Section: Discussionmentioning

confidence: 99%

“…18,19 Canadian studies have found that immune protection among LTC residents wanes much faster than younger, healthier adults after 2 doses; similar patterns may be expected for booster doses. 39,40 Studies from the United Kingdom (UK) among adults suggest similar levels of protection from a third dose of either mRNA vaccine against symptomatic Omicron infection irrespective of the mRNA product used for the primary series. 16,38 Among adults aged ≥65 years in the UK, VE against hospitalization was also similar for a third dose of either mRNA vaccine following 2 doses of BNT162b2.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada: Test-Negative Design Study

Grewal

Kitchen

Nguyen

et al. 2022

Preprint

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BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine ≥84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant.MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged ≥60 years who were tested for SARS-CoV-2 between December 30, 2021 and March 2, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death).ResultsWe included 9,957 Omicron cases and 46,849 test-negative controls. The marginal effectiveness of a fourth dose ≥7 days after vaccination versus a third dose received ≥84 days prior was 40% (95% Confidence Interval[CI], 34-45%) against infection, 63% (95%CI, 51-71%) against symptomatic infection, and 54% (95%CI, 31-70%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 65% (95%CI, 60-70%), 87% (95%CI, 81-91%), and 92% (95%CI, 87-95%), against infection, symptomatic infection, and severe outcomes, respectively.ConclusionsOur findings suggest that compared to a third dose received ≥84 days ago, a fourth dose recommendation for LTC residents improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron. Compared to unvaccinated individuals, fourth doses provide strong protection against symptomatic infection and severe outcomes but the duration of protection remains unknown.

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“…Additionally, these assays are used in > 30 studies focused on infection and/or vaccine responses across different cohorts, e.g. in persons predicted to have a weaker immune response (based, for example on age 37 or health conditions 38 ), or who are likely to be exposed to infection from the workplace. The results of the assays have critically helped informed public health decisions.…”

Section: Discussionmentioning

confidence: 99%

A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

Colwill

Galipeau

Stuible

et al. 2021

Preprint

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BACKGROUND: Testing for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable "Made-in-Canada" solution that can detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. METHODS: We developed a set of methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD), and the nucleocapsid (N) protein. These antigens are complemented by a detection antibody (human anti-IgG fused to horseradish peroxidase (HRP)) and a positive control reference antibody (recombinant IgG against the RBD), permitting intra- and inter-laboratory comparisons. Using this toolkit and commercial reagents, we optimized automated ELISAs on two different high throughput platforms to measure antibody responses to SARS-CoV-2 antigens. The assays were calibrated to a reference standard from the World Health Organization. We also automated a surrogate neutralization (sn)ELISA that measures inhibition of ACE2-Spike or -RBD interactions by antibodies using biotinylated ACE2. RESULTS: Our individual IgG-based ELISAs measure antibody levels in single-point measurements in reference to a standard antibody curve to accurately distinguish non-infected and infected individuals (area under the curve > 0.96 for each assay). Positivity thresholds can be established in individual assays using precision-recall analysis (e.g., by fixing the false positive rate), or more stringently, by scoring against the distribution of the means of negative samples across multiple assays performed over several months. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for at least 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. Here, we present detailed protocols to perform these assays using either serum/plasma or dried blood spots both manually and on two automated platforms, and to express the results in international units to facilitate data harmonization and inter-study comparisons. We also demonstrate that the snELISA can be performed automatically at single points, increasing the scalability of this functional assay for large seroprevalence studies. INTERPRETATION: The ability to measure antibodies to three viral antigens and identify neutralizing antibodies capable of disrupting spike-ACE2 interactions in high-throughput assays enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The "Made-in-Canada" set of protein reagents, produced at the National Research Council of Canada are publicly available to enable the up-scaling of standardized serological assays, permitting nationwide data comparison and aggregation.

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Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study

Cited by 9 publications

References 33 publications

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada: Test-Negative Design Study

A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

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