mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals
Issued Date
2022-09-08
Resource Type
eISSN
16643224
Scopus ID
2-s2.0-85138533453
Pubmed ID
36159846
Journal Title
Frontiers in Immunology
Volume
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Immunology Vol.13 (2022)
Suggested Citation
Longet S., Hargreaves A., Healy S., Brown R., Hornsby H.R., Meardon N., Tipton T., Barnes E., Dunachie S., Duncan C.J.A., Klenerman P., Richter A., Turtle L., de Silva T.I., Carroll M.W. mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals. Frontiers in Immunology Vol.13 (2022). doi:10.3389/fimmu.2022.953949 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84908
Title
mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals
Author's Affiliation
Oxford University Hospitals NHS Foundation Trust
Liverpool University Hospitals NHS Foundation Trust
The Wellcome Centre for Human Genetics
University of Oxford
University Hospitals Birmingham NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University of Liverpool
University of Birmingham
Mahidol University
Nuffield Department of Medicine
Newcastle University
The University of Sheffield
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Liverpool University Hospitals NHS Foundation Trust
The Wellcome Centre for Human Genetics
University of Oxford
University Hospitals Birmingham NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University of Liverpool
University of Birmingham
Mahidol University
Nuffield Department of Medicine
Newcastle University
The University of Sheffield
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Other Contributor(s)
Abstract
Two doses of BNT162b2 mRNA vaccine induces a strong systemic SARS-CoV-2 specific humoral response. However, SARS-CoV-2 airborne transmission makes mucosal immune response a crucial first line of defense. Therefore, we characterized SARS-CoV-2-specific IgG responses induced by BNT162b2 vaccine, as well as IgG responses to other pathogenic and seasonal human coronaviruses in oral fluid and plasma from 200 UK healthcare workers who were naïve (N=62) or previously infected with SARS-CoV-2 (N=138) using a pan-coronavirus multiplex binding immunoassay (Meso Scale Discovery®). Additionally, we investigated the impact of historical SARS-CoV-2 infection on vaccine-induced IgG, IgA and neutralizing responses in selected oral fluid samples before vaccination, after a first and second dose of BNT162b2, as well as following a third dose of mRNA vaccine or breakthrough infections using the same immunoassay and an ACE2 inhibition assay. Prior to vaccination, we found that spike-specific IgG levels in oral fluid positively correlated with IgG levels in plasma from previously-infected individuals (Spearman r=0.6858, p<0.0001) demonstrating that oral fluid could be used as a proxy for the presence of plasma SARS-CoV-2 IgG. However, the sensitivity was lower in oral fluid (0.85, 95% CI 0.77-0.91) than in plasma (0.94, 95% CI 0.88-0.97). Similar kinetics of mucosal and systemic spike-specific IgG levels were observed following vaccination in naïve and previously-infected individuals, respectively. In addition, a significant enhancement of OC43 and HKU1 spike-specific IgG levels was observed in previously-infected individuals following one vaccine dose in oral fluid (OC43 S: p<0.0001; HKU1 S: p=0.0423) suggesting cross-reactive IgG responses to seasonal beta coronaviruses. Mucosal spike-specific IgA responses were induced by mRNA vaccination particularly in previously-infected individuals (71%) but less frequently in naïve participants (23%). Neutralizing responses to SARS-CoV-2 ancestral and variants of concerns were detected following vaccination in naïve and previously-infected participants, with likely contribution from both IgG and IgA in previously-infected individuals (correlations between neutralizing responses and IgG: Spearman r=0.5642, p<0.0001; IgA: Spearman r=0.4545, p=0.0001). We also observed that breakthrough infections or a third vaccine dose enhanced mucosal antibody levels and neutralizing responses. These data contribute to show that a previous SARS-CoV-2 infection tailors the mucosal antibody profile induced by vaccination.