登入
選單
返回
Google圖書搜尋
Class Switch Towards Non-inflammatory, Spike-specific IgG4 Antibodies After Repeated SARS-CoV-2 MRNA Vaccination
Pascal Irrgang
Juliane Gerling
Katharina Kocher
Dennis Lapuente
Philipp Steininger
Katharina Habenicht
Monika Wytopil
Stephanie Beileke
Simon T. Schäfer
Jahn Zhong
George Ssebyatika
Thomas Krey
Valeria Falcone
Christine Schülein
Antonia Sophia Peter
Krystelle Nganou-Makamdop
Hartmut Hengel
Jürgen Held
Christian Bogdan
Klaus Thomas Überla
Kilian Schober
Thomas H. Winkler
Matthias Tenbusch
出版
Universität
, 2023
URL
http://books.google.com.hk/books?id=4z7NzwEACAAJ&hl=&source=gbs_api
註釋
Abstract: RNA vaccines are efficient preventive measures to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. High levels of neutralizing SARS-CoV-2 antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the immunoglobulin G (IgG) response mainly consists of the proinflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of noninflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose, on average, from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B cell population [median of 14.4%; interquartile range (IQR) of 6.7 to 18.1%] compared with the overall memory B cell repertoire (median of 1.3%; IQR of 0.9 to 2.2%) after three immunizations. This class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Because Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2