Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant
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Abstract
To examine COVID-19 mRNA vaccine–induced binding and neutralizing antibody responses in patients with non–small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination.
METHODS
Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively.
RESULTS
A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses.
CONCLUSION
A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.
Article activity feed
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Chetna Mangat
Review 1: "Antibody Response to SARS-CoV-2 mRNA Vaccine in Lung Cancer Patients: Reactivity to Vaccine Antigen and Variants of Concern"
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Strength of evidence
Reviewer: C Mangat (Mayo Clinic) | 📗📗📗📗◻️
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SciScore for 10.1101/2022.01.03.22268599: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: NSCLC patient cohort: Peripheral blood samples from NSCLC patients were collected at Winship Cancer Institute following written informed consent approved by the Institutional Review Board at Emory University.
IRB: NSCLC patient cohort: Peripheral blood samples from NSCLC patients were collected at Winship Cancer Institute following written informed consent approved by the Institutional Review Board at Emory University.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources MesoScale Discovery Assay: V-PLEX COVID-19 Respiratory Panel 2 Kit … SciScore for 10.1101/2022.01.03.22268599: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: NSCLC patient cohort: Peripheral blood samples from NSCLC patients were collected at Winship Cancer Institute following written informed consent approved by the Institutional Review Board at Emory University.
IRB: NSCLC patient cohort: Peripheral blood samples from NSCLC patients were collected at Winship Cancer Institute following written informed consent approved by the Institutional Review Board at Emory University.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources MesoScale Discovery Assay: V-PLEX COVID-19 Respiratory Panel 2 Kit (K15372U panel 2) were used to measure the IgG, IgM and IgA antibody against the antigens SARS-CoV-2 Spike, receptod binding domain (RBD), antigens SARS-CoV-2 Spike , receptod binding domain ( RBD) ,suggested: NoneFollowing this, 50 uL per well of 1X MSD SULFO-TAG™ Anti-Human IgG Antibody was added and incubated for one hour at room temperature, shaking at a speed of 700 rpm. Anti-Human IgGsuggested: NoneCells were incubated with either an anti-SARS-CoV spike primary antibody directly conjugated to Alexaflour-647 (CR3022-AF647) or an anti-SARS-CoV spike primary antibody directly conjugated to biotin (CR3022-biotin) for at least 4 hours at room temperature. CR3022-AF647suggested: Noneanti-SARS-CoV spikesuggested: NoneCR3022-biotinsuggested: NoneExperimental Models: Cell Lines Sentences Resources Viruses and cells: VeroE6 cells were obtained from ATCC (clone E6, ATCC, #CRL-1586) and cultured in complete DMEM medium consisting of 1x DMEM (VWR, #45000-304), 10% FBS, 25mM HEPES Buffer (Corning Cellgro), 2mM L-glutamine, 1mM sodium pyruvate, 1x Non-essential Amino Acids, and 1x antibiotics. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)VeroE6-TMPRSS2 cells were generated and cultured as previously described18. nCoV/USA_WA1/2020 (WA/1), closely resembling the original Wuhan strain and resembles the spike used in the mRNA-1273 and Pfizer-BioNTech vaccine, was propagated from an infectious SARS-CoV-2 clone as previously described19. VeroE6-TMPRSS2suggested: NoneUsing VeroE6-TMPRSS cells, the B.1.1.529 variant was plaque purified directly from the nasal swab, propagated once in a 12-well plate, and expanded in a confluent T175 flask to generate a working stock. VeroE6-TMPRSSsuggested: NoneFocus Reduction Neutralization Assay: FRNT-mNG assays were performed on VeroE6 cells and FRNT assays were performed on Vero-TMPRSS2 cells as previously described18,21,22. Vero-TMPRSS2suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)Software and Algorithms Sentences Resources Statistical analysis: Statistical analysis was conducted using Graphpad Prism V9 and R 4.1.2. Graphpad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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.
Results from scite Reference Check: We found no unreliable references.
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