SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence
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Abstract
T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5 + PD1 + CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.
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SciScore for 10.1101/2020.10.07.20208488: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethics statement: All patients included in this study were adults and recruited from the University of Alabama at Birmingham (UAB) HIV care clinic, also known as the 1917 clinic, after obtaining written, informed consent and approval from the IRB-160125005 at UAB. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After an 18 hour incubation at 37°C, cells were washed with FACS wash (2% FBS in PBS), stained with CCR7-PercpCy5.5 at 37°C for 20 min, washed, and then stained with the following antibodies: … SciScore for 10.1101/2020.10.07.20208488: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Ethics statement: All patients included in this study were adults and recruited from the University of Alabama at Birmingham (UAB) HIV care clinic, also known as the 1917 clinic, after obtaining written, informed consent and approval from the IRB-160125005 at UAB. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After an 18 hour incubation at 37°C, cells were washed with FACS wash (2% FBS in PBS), stained with CCR7-PercpCy5.5 at 37°C for 20 min, washed, and then stained with the following antibodies: CD4-Pe610, CD3-A780, CD8-FITC, CD14-A700, CD19-A700, Ox40-PeCy7, PDL1-PE, CXCR5-BV421, PD1-BV785, CD45RA-BV510, CD137-BV650, CD69-BUV737, and Dead cell dye-UV. CD8-FITCsuggested: NoneCXCR5-BV421suggested: NoneCD69-BUV737suggested: NoneAntibody assays: Plasma samples from the first time point for all 21 individuals were tested for SARS-CosV-2-specific antibodies. SARS-CosV-2-specificsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, the SARS-CoV-2 Spike (Wuhan 1, with a 19 amino acid cytoplasmic tail deletion) was pseudotyped onto an HV-1 nanoluciferase reporter backbone by co-transfection in HEC 293T cells. HEC 293Tsuggested: NonePseudovirus was incubated with five-fold serial dilutions of patient plasma and then used to infect 1.5×104 293T clone 13 cells expressing ACE2. 293T clone 13suggested: RRID:CVCL_VR13)Software and Algorithms Sentences Resources Clinical data from these individuals were retrieved from the Enterprise Biorepository REDCap database (43). REDCapsuggested: (REDCap, RRID:SCR_003445)Events were collected on a BD FACSymphony A3 within 24 hours and analyzed using FlowJo software ( FlowJosuggested: (FlowJo, RRID:SCR_008520)The Abbott Architect assay was used to detect immunoglobin G (IgG) reactivity to the SARS-CoV-2 nucleocapsid protein (46). Abbott Architectsuggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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