Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike
Pre-existing antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2021 |
|---|---|
| Enthalten in: |
medRxiv : the preprint server for health sciences - (2021) vom: 28. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Crowley, Andrew R [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 04.04.2024 published: Electronic UpdateIn: Elife. 2022 Mar 15;11:. - PMID 35289271 Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2021.10.27.21265574 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM33267732X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM33267732X | ||
| 003 | DE-627 | ||
| 005 | 20240404232728.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2021.10.27.21265574 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1364.xml |
| 035 | |a (DE-627)NLM33267732X | ||
| 035 | |a (NLM)34729565 | ||
| 035 | |a (PII)2021.10.27.21265574 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Crowley, Andrew R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 04.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Elife. 2022 Mar 15;11:. - PMID 35289271 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Pre-existing antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Natarajan, Harini |e verfasserin |4 aut | |
| 700 | 1 | |a Hederman, Andrew P |e verfasserin |4 aut | |
| 700 | 1 | |a Bobak, Carly A |e verfasserin |4 aut | |
| 700 | 1 | |a Weiner, Joshua A |e verfasserin |4 aut | |
| 700 | 1 | |a Wieland-Alter, Wendy |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jiwon |e verfasserin |4 aut | |
| 700 | 1 | |a Bloch, Evan M |e verfasserin |4 aut | |
| 700 | 1 | |a Tobian, Aaron A R |e verfasserin |4 aut | |
| 700 | 1 | |a Redd, Andrew D |e verfasserin |4 aut | |
| 700 | 1 | |a Blankson, Joel N |e verfasserin |4 aut | |
| 700 | 1 | |a Wolf, Dana |e verfasserin |4 aut | |
| 700 | 1 | |a Goetghebuer, Tessa |e verfasserin |4 aut | |
| 700 | 1 | |a Marchant, Arnaud |e verfasserin |4 aut | |
| 700 | 1 | |a Connor, Ruth I |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Peter F |e verfasserin |4 aut | |
| 700 | 1 | |a Ackerman, Margaret E |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t medRxiv : the preprint server for health sciences |d 2020 |g (2021) vom: 28. Okt. |w (DE-627)NLM310900166 |7 nnns |
| 773 | 1 | 8 | |g year:2021 |g day:28 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2021.10.27.21265574 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2021 |b 28 |c 10 | ||