TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Wietschel, Kilian A.
A1  - Fechtner, Kevin
A1  - Antileo, Elmer
A1  - Abdurrahman, Goran
A1  - Drechsler, Chiara A.
A1  - Makuvise, Michelle K.
A1  - Rose, Ruben
A1  - Voß, Mathias
A1  - Krumbholz, Andi
A1  - Michalik, Stephan
A1  - Weiss, Stefan
A1  - Ulm, Lena
A1  - Franikowski, Philipp
A1  - Fickenscher, Helmut
A1  - Bröker, Barbara M.
A1  - Raafat, Dina
A1  - Holtfreter, Silva
T1  - Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination – kinetics of plasma antibodies, plasmablasts and memory B cells
JF  - Frontiers in Immunology
N2  - Introduction

COVID-19 vaccines are highly effective in inducing protective immunity. While the serum antibody response to COVID-19 vaccination has been studied in depth, our knowledge of the underlying plasmablast and memory B cell (Bmem) responses is still incomplete. Here, we determined the antibody and B cell response to COVID-19 vaccination in a naïve population and contrasted it with the response to a single influenza vaccination in a primed cohort. In addition, we analyzed the antibody and B cell responses against the four endemic human coronaviruses (HCoVs). 

Methods

Measurement of specific plasma IgG antibodies was combined with functional analyses of antibody-secreting plasmablasts and Bmems. SARS-CoV-2- and HCoV-specific IgG antibodies were quantified with an in-house bead-based multiplexed immunoassay. 
                
Results

The antibody and B cell responses to COVID-19 vaccination reflected the kinetics of a prime-boost immunization, characterized by a slow and moderate primary response and a faster and stronger secondary response. In contrast, the influenza vaccinees possessed robust immune memory for the vaccine antigens prior to vaccination, and the recall vaccination moderately boosted antibody production and Bmem responses. Antibody levels and Bmem responses waned several months after the 2 nd COVID-19 vaccination, but were restored upon the 3 rd vaccination. The COVID-19 vaccine-induced antibodies mainly targeted novel, non-cross-reactive S1 epitopes of the viral spike protein, while cross-reactive S2 epitopes were less immunogenic. Booster vaccination not only strongly enhanced neutralizing antibodies against an original SARS-CoV-2 strain, but also induced neutralizing antibodies against the Omicron BA.2 variant. We observed a 100% plasma antibody prevalence against the S1 subunits of HCoVs, which was not affected by vaccination. 

Discussion

Overall, by complementing classical serology with a functional evaluation of plasmablasts and memory B cells we provide new insights into the specificity of COVID-19 vaccine-induced antibody and B cell responses.
KW  - COVID-19 vaccination
KW  - dynamics
KW  - cross-reactive antibodies
KW  - plasmablast
KW  - memory B cell
KW  - HCoV
KW  - influenza
KW  - original antigenic sin
Y1  - 2024
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-111030
SN  - 1664-3224
SS  - 1664-3224
U6  - https://doi.org/10.3389/fimmu.2024.1382911
DO  - https://doi.org/10.3389/fimmu.2024.1382911
VL  - 15
SP  - 16
S1  - 16
PB  - Frontiers Media S.A.
CY  - Lausanne
ER  -