Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination

Schaefer-Babajew, Dennis; Wang, Zijun; Muecksch, Frauke; Cho, Alice; Loewe, Maximilian; Cipolla, Melissa; Raspe, Raphael; Johnson, Brianna; Canis, Marie; DaSilva, Justin; Ramos, Víctor; Turroja, Martina; Millard, Katrina G.; Schmidt, Fabian; Witte, Leander; Dizon, Juan; Shimelovich, Irina; Yao, Kai-Hui; Oliveira, Thiago Y.; Gazumyan, Anna; Gaebler, Christian; Bieniasz, Paul D.; Hatziioannou, Théodora; Caskey, Marina; Nussenzweig, Michel C.

doi:10.1038/s41586-022-05609-w

Cited by 89 publications

(81 citation statements)

References 44 publications

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“…We also observed much higher levels of neutralizing antibodies against the Omicron variant after the booster vaccination compared with those after 2 doses of the vaccine. This finding may indicate that the booster vaccination achieves a sufficient induction of immunity against the Omicron variant and would likely achieve sufficient immunity against other future variants by inducing neutralizing antibodies that recognize common epitopes and by promoting affinity maturation of the antibody …”

Section: Discussionmentioning

confidence: 99%

Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

et al. 2022

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Key Points Question Are neutralizing antibodies against the Omicron variant of SARS-CoV-2 sufficiently induced after 2 to 3 doses of the BNT162b2 messenger RNA vaccine in recipients of different ages? Findings In this cohort study of 82 Japanese participants, 28% and 6% had neutralizing antibodies against the Omicron variant at 2 and 7 months, respectively, after 2 doses of the vaccine; both titer values were low in all age groups. After receiving a booster vaccination, all participants acquired much higher levels of neutralizing antibodies irrespective of age. Meaning This study suggests that booster vaccination was associated with induction of higher levels of neutralizing antibodies against the Omicron variant, irrespective of the recipient’s age.

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Section: Discussionmentioning

confidence: 99%

Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

et al. 2022

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“…This delay, however, is not observed in the setting of SARS-CoV-2 mRNA 12 or influenza 47 vaccination, where plasmablasts in the blood are detected with similar kinetics as new antibody. It is possible that B cell activation may be moderately impaired by a suppressive effect of pre-existing antibodies masking antigen binding sites 69, 70 . Antibody may also be bound by Spike antigen in immune complexes during the early stages of infection, precluding detection in neutralizing or binding antibody assays.…”

Section: Discussionmentioning

confidence: 99%

“…By the time symptoms are experienced, immune recall responses could already be underway. Early activation of memory B cells and plasmablasts could drive rapid production of Spike-specific antibodies, potentially clearing virus quickly enough to blunt activation of memory T cells and impede the generation of new primary immune responses against non-Spike antigens or novel variant Spike epitopes 41 . Alternatively, if pre-existing antibody titers are low and new production of antibody lags, memory T cells could play a key role in controlling viral replication during the early phase of infection, thus limiting viral spread and disease progression.…”

Section: Introductionmentioning

confidence: 99%

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies

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Lundgreen

et al. 2023

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SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

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“…The predominant antibodies produced at the early stage may dampen the selection of B cells specific to the predominant epitopes at the later stage and the next vaccination, resulting in a change in the predominant epitopes of the B cell repertoire over time. A study demonstrated that antibody feedback by monoclonal antibodies alters epitopes of B mem cells induced by COVID-19 vaccination [ 106 ].…”

Section: Main Textmentioning

confidence: 99%

Humoral immunity for durable control of SARS-CoV-2 and its variants

2023

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The coronavirus disease 2019 (COVID-19) pandemic is ongoing because of the repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, highlighting the importance of developing vaccines for variants that may continue to emerge. In the present review, we discuss humoral immune responses against SARS-CoV-2 with a focus on the antibody breadth to the variants. Recent studies have revealed that the temporal maturation of humoral immunity improves the antibody potency and breadth to the variants after infection or vaccination. Repeated vaccination or infection further accelerates the expansion of the antibody breadth. Memory B cells play a central role in this phenomenon, as the reactivity of the B-cell antigen receptor (BCR) on memory B cells is a key determinant of the antibody potency and breadth recalled upon vaccination or infection. The evolution of memory B cells remarkably improves the reactivity of BCR to antigenically distinct Omicron variants, to which the host has never been exposed. Thus, the evolution of memory B cells toward the variants constitutes an immunological basis for the durable and broad control of SARS-CoV-2 variants.

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Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination

Cited by 89 publications

References 44 publications

Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies

Humoral immunity for durable control of SARS-CoV-2 and its variants

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