scholarly journals SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike

2020 ◽  
Author(s):  
Jenna J. Guthmiller ◽  
Olivia Stovicek ◽  
Jiaolong Wang ◽  
Siriruk Changrob ◽  
Lei Li ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Cell Response ◽  
Nucleocapsid Protein ◽  
Antigen Specificity ◽  
Memory B Cell ◽  
Reading Frame ◽  
Global Pandemic ◽  
Kinetics Of ◽  
B Cell Response

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.

scholarly journals SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jenna J. Guthmiller ◽  
Olivia Stovicek ◽  
Jiaolong Wang ◽  
Siriruk Changrob ◽  
Lei Li ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Cell Response ◽  
Nucleocapsid Protein ◽  
Severe Disease ◽  
Natural Immunity ◽  
Antigen Specificity ◽  
Memory B Cell ◽  
Viral Antigens ◽  
B Cell Response

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike. IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

scholarly journals Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bing He ◽  
Shuning Liu ◽  
Yuanyuan Wang ◽  
Mengxin Xu ◽  
Wei Cai ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Cell Response ◽  
Critical Role ◽  
Antigen Specificity ◽  
Memory B Cell ◽  
Specific Memory ◽  
B Cell Response

AbstractB cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chighCD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.

scholarly journals Measuring the cellular memory B cell response after vaccination in patients after allogeneic stem cell transplantation

2020 ◽  
Vol 99 (8) ◽  
pp. 1895-1906
Author(s):  
Julia Winkler ◽  
Hannes Tittlbach ◽  
Andrea Schneider ◽  
Corinna Buchstaller ◽  
Andreas Mayr ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Response ◽  
Cellular Memory ◽  
Memory B Cell ◽  
B Cell Response

scholarly journals Specific memory B cell response in humans upon infection with highly pathogenic H7N7 avian influenza virus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Brenda Westerhuis ◽  
Hinke ten Hulscher ◽  
Ronald Jacobi ◽  
Josine van Beek ◽  
Marion Koopmans ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
B Cell ◽  
Avian Influenza Virus ◽  
Cell Response ◽  
Highly Pathogenic ◽  
Memory B Cell ◽  
Specific Memory ◽  
B Cell Response

scholarly journals SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261656
Author(s):  
Raphael A. Reyes ◽  
Kathleen Clarke ◽  
S. Jake Gonzales ◽  
Angelene M. Cantwell ◽  
Rolando Garza ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Symptom Onset ◽  
Cell Response ◽  
Severe Disease ◽  
Memory B Cells ◽  
Memory B Cell ◽  
Specific Memory ◽  
Specific Igg ◽  
B Cell Response

SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG+ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG+ B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet+ spike-specific IgG+ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet+ IgG+ memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

scholarly journals Bivalent oral cholera vaccination induces a memory B cell response to the V. cholerae O1-polysaccharide antigen in Haitian adults

2019 ◽  
Vol 13 (1) ◽  
pp. e0007057 ◽  
Author(s):  
Brie Falkard ◽  
Richelle C. Charles ◽  
Wilfredo R. Matias ◽  
Leslie M. Mayo-Smith ◽  
J. Gregory Jerome ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Response ◽  
Polysaccharide Antigen ◽  
Memory B Cell ◽  
Cholera Vaccination ◽  
B Cell Response

scholarly journals The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes

2017 ◽  
Vol 91 (9) ◽  
Author(s):  
Clare F. J. Grant ◽  
B. Veronica Carr ◽  
Abhay Kotecha ◽  
Erwin van den Born ◽  
David I. Stuart ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Virus ◽  
Cell Response ◽  
Lymphoid Tissue ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Kinetics Of ◽  
B Cell Response

ABSTRACT Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV.

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