Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Al, McNaughton; Paton, Robert S; Edmans, Matthew; Youngs, Jonathan; Wellens, Judith; Phalora, Prabhjeet; Fyfe, Alex; Belij‐Rammerstorfer, Sandra; Js, Bolton; Ball, Jonathan K.; Carnell, George; Dejnirattisai, Wanwisa; Dold, Christina; Eyre, DW; Hopkins, Philip; Howarth, Alison; Kooblall, Kreepa; Klim, Hannah; Leaver, Susannah; L, Lee; López-Camacho, César; Lumley, Sheila F; Macallan, Derek C.; Aj, Mentzer; Provine, Nicholas M.; Ratcliff, Jeremy; Slon-Campos, Jose; Skelly, Donal; Stolle, Lucas; Supasa, Piyasa; Temperton, Nigel; Walker, Chris; Wang, B; Wyncoll, Duncan; Simmonds, Peter; Lambe, Teresa; Baillie, J Kenneth; Semple, Malcolm G; Openshaw, Peter; Investigators, Isaric C; Obolski, Uri; Turner, Marc; Mw, Carroll; Mongkolspaya, Juthathip; Screaton, Gavin; Sh, Kennedy; Jarvis, Lisa; Barnes, Eleanor; Dunachie, Susanna; Lourenço, José; Matthews, Philippa C.; Bicanic, Tihana; Klenerman, Paul; Gupta, Sunetra; Thompson, Craig

doi:10.1101/2021.05.04.21256571

Cited by 13 publications

(11 citation statements)

References 28 publications

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“…It is unknown if the recall of β-hCoV antibodies upon SARS-CoV-2 infections impacts disease outcome. A recent study suggests that the recall of OC43 β-hCoV antibodies is associated with a compromised de novo SARS-CoV-2 response in individuals with fatal COVID-19 37 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

Anderson

Eiloa

Goodwin

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

Anderson

Eiloa

Goodwin

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The use of S1 as an immunogen has been proposed for other highly pathogenic coronaviruses, such as MERS-CoV and SARS-CoV, because of its potential high safety profile compared to the use of full-length S. Although full-length S protein can induce the highest immune response, some reports suggested its association with possible side effects in the currently used COVID-19 vaccines [22,23]. Additionally, previous reports on MERS-CoV, SARS-CoV and other coronaviruses have suggested that the use of a fulllength S based vaccine could lead to undesired immune response upon infection [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…Most of these aforementioned vaccines rely on using either the full-length S protein or the RBD as the immunogen because of their critical roles in viral entry and host tropism [19,20], and ability to elicit protective immunity in animals and humans after vaccination or infection [9,10,21]. Use of fulllength S protein as immunogen, however, could be associated with undesired responses by inducing non-neutralizing antibodies which may contribute to disease enhancement, immunopathological inflammation and fatality [22][23][24][25][26][27][28]. As such, targeting the S1 subunit could help minimize a potentially undesirable effect.…”

Section: Introductionmentioning

confidence: 99%

Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

et al. 2021

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The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

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“…The use of S1 as an immunogen has been proposed for other highly pathogenic coronaviruses such as MERS-CoV and SARS-CoV because its potential high safety profile compared to the use of full-length S. Although full-length S protein can induce the highest immune response, some reports suggest its association with possible side effects in the currently used COVID-19 vaccines [22,23]. Additionally, previous reports on MERS-CoV, SARS-CoV and other coronaviruses have suggested that the use of full-length S based vaccine could lead to undesired immune response upon infection [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…Most of these aforementioned vaccines rely on using either the full-length S protein or the RBD as the immunogen because of their critical roles in viral entry and host tropism [19,20], and ability to elicit protective immunity in animals and humans after vaccination or infection [9,10,21]. Use of full-length S protein as immunogen, however, could be associated with undesired responses by inducing non-neutralizing antibodies which may contribute to disease enhancement, immunopathological inflammation and fatality [22][23][24][25][26][27][28]. As such, targeting the S1 subunit could help minimize potentially undesirable effect.…”

Section: Introductionmentioning

confidence: 99%

Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Alluhaybi

Alharbi

Alhabbab

et al. 2021

Preprint

View full text Add to dashboard Cite

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

show abstract

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Cited by 13 publications

References 28 publications

SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

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