A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2

Majdoubi, Abdelilah; Michalski, Christina; O’Connell, Sarah; Dada, Sarah; Narpala, Sandeep; Gelinas, Jean Pierre; Mehta, Disha; Cheung, Claudia; Winkler, Dirk; Basappa, Manjula; Liu, Aaron C.; Görges, Matthias; Barakauskas, Vilte; Irvine, Michael; Mehalko, Jennifer; Esposito, Dominic; Sekirov, Inna; Jassem, Agatha N; Goldfarb, David M.; Pelech, Steven; Douek, Daniel C.; McDermott, Adrian B.; Lavoie, Pascal M.

doi:10.1172/jci.insight.146316

Cited by 47 publications

(53 citation statements)

References 30 publications

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“…Findings are in keeping with modelling studies 31,32 and data from the UK where low seroprevalence was also measured in teachers, but this was earlier in the pandemic 15 . Moreover, despite that the seroprevalence in this study represents an approximately threefold increase relative to previous estimates of 0.55% to 0.6% obtained from Vancouver residents in spring 2020 [33][34][35] , it remained comparable to age/sex and area of residency-matched blood donors.…”

Section: Discussioncontrasting

confidence: 94%

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada

Goldfarb

Mâsse

Watts

et al. 2021

Preprint

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Importance: Contact-tracing studies suggest minimal secondary transmission in schools. However, there are limited school data accounting for asymptomatic cases, particularly late in the 2020/21 school year, and in the context of uninterrupted in-person schooling and widespread community transmission. Objectives: To determine the SARS-CoV-2 seroprevalence in a sample of school staff, compared to the community, and to COVID-19 rates among all students and staff within the same school population. Design: Incident COVID-19 cases among students and school staff using public health data, with an embedded cross-sectional serosurvey among school staff sampled from February 10 to May 15, 2021, comparing to age, sex and geographic location-matched blood donors sampled in January 2021. Setting: Vancouver School District (British Columbia, Canada) from kindergarten to grade 12. Participants: Active school staff enrolled from February 3 to April 23, 2021. Main outcome measures: SARS-CoV-2 antibodies in a sample of school staff using spike (S)-based testing (unvaccinated staff) or N-based serology testing (vaccinated staff). Results: The incidence of COVID-19 cases among students attending in-person was 9.8 per 1,000 students during the 2020/21 school year (N = 47,280 students), and among staff was 13 per 1,000 since the beginning of the pandemic (N = 7,071 active school staff). In total, 1,689 school staff (64% elementary, 28% secondary, 8.3% school board staff or multiple grades) completed the questionnaire, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week [IQR: 5.0 - 25 hours]. Although 21.5% (363/1,686) reported close contact with a COVID-19 case, only 1.4% (24/1688) of the school staff reported having had a positive viral nucleic acid test. Of this group, five believed they acquired the infection at school. The adjusted seroprevalence in staff who gave blood (1,556/1,689, 92.1%) was 2.3% [95%CI: 1.6 - 3.2%] compared to 2.3% [95%CI: 1.7 - 3.0%] in blood donors. Conclusion and relevance: Despite high reported COVID-19 cases among students and staff, and frequent within-school exposures, we found no detectable increase in seroprevalence among school staff above the community seroprevalence. These findings corroborate claims that, with appropriate mitigation strategies, in-person schooling is not associated with significantly increased risk for school staff.

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Section: Discussioncontrasting

confidence: 94%

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada

Goldfarb

Mâsse

Watts

et al. 2021

Preprint

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“…Overall, with this small sample of sera there was little difference between the patterns of reactivity of the sera from the sick and healthy groups. This high detection of anti-spike and anti-nucleocapsid immunoreactivity in serum samples from healthy individuals is consistent with previous studies using two different serological tests developed by Mesoscale Devices and Kinexus (31).…”

Section: Cbm9-sars-cov-2 Fusion Proteins React With Rabbit Anti-spike Protein Sera and Human Serasupporting

confidence: 92%

Escherichia coli recombinant expression of SARS-CoV-2 protein fragments

McGuire

Mela

Thompson

et al. 2021

Preprint

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We have developed a method for the inexpensive, high-level expression of antigenic protein fragments of SARS-CoV-2 proteins in Escherichia coli. Our approach used the thermophilic carbohydrate binding domain 9 (CBM9) module as an N-terminal carrier protein and affinity tag. The CBM9 module was joined to SARS-CoV-2 protein fragments via a flexible proline-threonine rich linker, which proved to be resistant to E. coli proteases. Two CBM9-spike protein fragment fusion proteins and one CBM9-nucleocapsid fragment fusion protein largely resisted protease degradation, while most of the CBM9-fusion proteins were degraded at some site in the SARS-CoV-2 protein fragment. All fusion proteins were expressed in E. coli at about 0.1 g/L, and could be purified with a single affinity binding step using inexpensive cellulose powder. Three purified CBM9-SARS-CoV-2 fusion proteins were tested and found to bind antibody directed to the appropriate SARS-CoV-2 antigenic region. The largest CBM9 fusion protein incorporates a spike protein self-folding domain, and includes amino acids 540-588 of the spike protein. This conserved region is immediately C-terminal to the receptor binding domain, is widely recognized by human convalescent sera, and contains a putative protective epitope.

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“…The absence of IgA2 antibodies specific for SARS-CoV-2 antigens in severely diseased COVID-19 patients has also been demonstrated [8], suggesting that mucosal anti-viral IgA antibodies may protect the host from a severe course of COVID-19. Several studies have reported the presence of RBD-binding antibodies in unexposed healthy individuals [9,10,11,12,13].…”

Section: Main Textmentioning

confidence: 99%

Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota

Ninnemann

Budzinski

Bondareva

et al. 2021

Preprint

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The commensal microflora is a source for multiple antigens that may induce cross-reactive antibodies against host proteins and pathogens. However, whether commensal bacteria can induce cross-reactive antibodies against SARS-CoV-2 remains unknown. Here we report that several commensal bacteria contribute to the generation of cross-reactive IgA antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. We identified SARS-CoV-2 unexposed individuals with RBD-binding IgA antibodies at their mucosal surfaces. Conversely, neutralising monoclonal anti-RBD antibodies recognised distinct commensal bacterial species. Some of these bacteria, such as Streptococcus salivarius, induced a cross-reactive anti-RBD antibodies upon supplementation in mice. Conversely, severely ill COVID-19 patients showed reduction of Streptococcus and Veillonella in their oropharynx and feces and a reduction of anti-RBD IgA at mucosal surfaces. Altogether, distinct microbial species of the human microbiota can induce secretory IgA antibodies cross-reactive for the RBD of SARS-CoV-2.

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A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2

Cited by 47 publications

References 30 publications

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada

Escherichia coli recombinant expression of SARS-CoV-2 protein fragments

Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota

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