TY - JOUR

T1 - Characterization of SARS-CoV-2 humoral immune response in a subject with unique sampling

T2 - A case report

AU - Walker, Melanie R.

AU - Idorn, Manja

AU - Bennett, Anja

AU - Søgaard, Max

AU - Salanti, Ali

AU - Ditlev, Sisse B.

AU - Barfod, Lea

N1 - Publisher Copyright: © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - Background: The development of vaccine candidates for COVID-19, and the administration of booster vaccines, has meant a significant reduction in COVID-19 related deaths world-wide and the easing of global restrictions. However, new variants of SARS-CoV-2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune-protection, primarily through binding to the SARS-COV-2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti-RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1–4) over the course of vaccination and breakthrough infection. Method: In this study, SARS-CoV-2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti-nucleocapsid total antibodies, anti-RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants. Results: Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition. Conclusion: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.

AB - Background: The development of vaccine candidates for COVID-19, and the administration of booster vaccines, has meant a significant reduction in COVID-19 related deaths world-wide and the easing of global restrictions. However, new variants of SARS-CoV-2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune-protection, primarily through binding to the SARS-COV-2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti-RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1–4) over the course of vaccination and breakthrough infection. Method: In this study, SARS-CoV-2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti-nucleocapsid total antibodies, anti-RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants. Results: Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition. Conclusion: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.

KW - antibody

KW - antibody isotypes

KW - antibody subclasses

KW - case report

KW - COVID-19

KW - humoral immunity

KW - IgG

KW - SARS-CoV-2

U2 - 10.1002/iid3.910

DO - 10.1002/iid3.910

M3 - Journal article

C2 - 37382252

AN - SCOPUS:85162126136

VL - 11

JO - Immunity, inflammation and disease

JF - Immunity, inflammation and disease

SN - 2050-4527

IS - 6

M1 - e910

ER -