mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Sokal, Aurélien; Barba-Spaeth, Giovanna; Fernández, Ignacio; Broketa, Matteo; Azzaoui, Imane; Selle, A.; Vandenberghe, Alexis; Fourati, Slim; Roeser, Anaïs; Meola, Annalisa; Bouvier‐Alias, Magali; Crickx, Étienne; Languille, Laetitia; Michel, Marc; Godeau, Bertrand; Gallien, Sébastien; Melica, Giovanna; Nguyen, Yann; Zarrouk, Virginie; Canouï‐Poitrine, Florence; Mégret, Jérôme; Pawlotsky, Jean‐Michel; Fillatreau, Simon; Bruhns, Pierre; Rey, F.A.; Weill, Jean‐Claude; Reynaud, Claude‐Agnès; Chappert, Pascal; Mahévas, Matthieu

doi:10.1016/j.immuni.2021.09.011

Cited by 112 publications

(141 citation statements)

References 77 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…The maturity of BMPCs was reflected in the significantly enhanced avidity of circulating anti-S IgG antibodies detected at six months compared to that measured at 2 weeks after the second vaccination. Our data corroborate multiple reports demonstrating the maturation of B cell responses after SARS-CoV-2 mRNA vaccination in humans 14,15,17,[25][26][27] . A potential limitation to our analyses of S-binding clones is that our selection strategy may have excluded some low-abundance or low-affinity S-specific clones.…”

Section: Discussionsupporting

confidence: 91%

“…Consistent with this notion, multiple reports have recently documented the evolution of circulating MBCs induced by SARS-CoV-2 mRNA vaccination in humans 14,15,17,26 . These reports have shown that not only the frequency of circulating S + MBCs increased over time, but their ability to recognize S proteins from emerging SARS-CoV-2 variants seems to have expanded as well 25,26 . These data indicate an important role for affinity maturation of responding B cell clones beyond increasing binding affinity to the immunizing antigen.…”

Section: Discussionmentioning

confidence: 54%

“…Under that framework, BMPCs secrete highly specific, high-affinity antibodies that provide the first layer of protection against the invading pathogen while MBCs would only be engaged in the event that a pathogen is not fully neutralized by BMPC-derived antibodies. Consistent with this notion, multiple reports have recently documented the evolution of circulating MBCs induced by SARS-CoV-2 mRNA vaccination in humans 14,15,17,26 . These reports have shown that not only the frequency of circulating S + MBCs increased over time, but their ability to recognize S proteins from emerging SARS-CoV-2 variants seems to have expanded as well 25,26 .…”

Section: Discussionmentioning

confidence: 54%

See 2 more Smart Citations

Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

Kim

Zhou

Sturtz

et al. 2021

Preprint

View full text Add to dashboard Cite

Germinal centres (GC) are lymphoid structures where vaccine-responding B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells (BMPCs)1–4. Induction of the latter is a hallmark of durable immunity after vaccination5. SARS-CoV-2 mRNA vaccination induces a robust GC response in humans6–8, but the maturation dynamics of GC B cells and propagation of their progeny throughout the B cell diaspora have not been elucidated. Here we show that anti-SARS-CoV-2 spike (S)-binding GC B cells were detectable in draining lymph nodes for at least six months in 10 out of 15 individuals who had received two doses of BNT162b2, a SARS-CoV-2 mRNA vaccine. Six months after vaccination, circulating S-binding MBCs were detected in all participants (n=42) and S-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of single-cell RNA sequencing of responding blood and lymph node B cells from eight participants and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1540 S-specific B cell clones. SHM accumulated along the B cell differentiation trajectory, with early blood plasmablasts showing the lowest frequencies, followed by MBCs and lymph node plasma cells whose SHM largely overlapped with GC B cells. By three months after vaccination, the frequency of SHM within GC B cells had doubled. Strikingly, S+ BMPCs detected six months after vaccination accumulated the highest level of SHM, corresponding with significantly enhanced anti-S polyclonal antibody avidity in blood at that time point. This study documents the induction of affinity-matured BMPCs after two doses of SARS-CoV-2 mRNA vaccination in humans, providing a foundation for the sustained high efficacy observed with these vaccines.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

Kim

Zhou

Sturtz

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…A second dose causes a second bigger immune response, which slowly decreases over time. However, a larger number of memory B cells pool (with higher affinity for antigen-affinity maturation) are left behind, helping stage a more extensive and faster immune response against the same pathogen in the future [ 16 , 17 , 18 , 19 , 20 ]. The Centers for Disease Control and Prevention (CDC) recommend a second dose of the Pfizer and Moderna COVID-19 vaccines [ 21 ].…”

Section: How Does the Covid Vaccine Workmentioning

confidence: 99%

COVID-19 Vaccine Booster: To Boost or Not to Boost

Shekhar

Garg

Pal

et al. 2021

Infectious Disease Reports

View full text Add to dashboard Cite

Developing safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a breakneck speed has been an exceptional human achievement. It remains our best hope of containing the coronavirus disease 2019 (COVID-19) pandemic. However, newer, more aggressive SARS-CoV-2 viral strains, as well as the possibility of fading immunity following vaccination, have prompted health officials to investigate the necessity for additional immunization. This has put further pressure on disregarded human life in lower-income countries that already have minimal access to COVID-19 vaccines. The Centers for Disease Control and Prevention (CDC) have recommended a third COVID-19 vaccine dose in immunocompromised individuals in a recent announcement. Governments and health care officials need to develop usage guidelines for COVID-19 vaccine booster doses while considering the dangers of potential waning immunity and new viral strains and prioritizing vulnerable populations everywhere, including those living in lower-income countries.

show abstract

“…One possibility is that plasma neutralization, to a greater extent, reflects the functionality of the long-lived plasma cells in the bone marrow 27 . The MBC response is another important type of immune protection, whose quantity and quality contribute to the speed and potency of the immune system responding to viral reinfection 28 . Both factors collectively provide vaccine recipients with antibody protection against viral infection or prevent them from developing severe disease.…”

Section: Discussionmentioning

confidence: 99%

Potent antibody immunity to SARS-CoV-2 variants elicited by a third dose of inactivated vaccine

Zhou

Song

et al. 2021

Preprint

View full text Add to dashboard Cite

SummarySARS-CoV-2 variants are still prevalent worldwide and continue to pose a challenge to the effectiveness of current vaccines. It remains unknown whether a third dose of inactivated vaccine elicits immune potential against SARS-CoV-2 variants. Here, we showed a significant decline in plasma neutralization against SARS-CoV-2 at seven months after a second dose of the inactivated vaccine in a large-scale cohort. However, we also found that a third vaccination with an inactivated vaccine largely increased plasma neutralization against variants including Beta, Delta, and Lambda. More importantly, the high-affinity anti-RBD memory B cells were also generated by the third vaccination, suggesting a more potent and longer protection. These findings highlighted the importance and effectiveness of a third dose of inactivated vaccine in conferring higher protection against the emerging variants in populations.

show abstract

mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Cited by 112 publications

References 77 publications

Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

COVID-19 Vaccine Booster: To Boost or Not to Boost

Potent antibody immunity to SARS-CoV-2 variants elicited by a third dose of inactivated vaccine

Contact Info

Product

Resources

About