mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

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1. Version published to 10.1016/j.xcrm.2022.100653

   Jun 1, 2022
2. 

   ScreenIT

   Feb 1, 2022

   SciScore for 10.1101/2022.01.26.22269848: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics

   IRB: Patients and samples: The study was approved by the Institutional Review Board of Washington University School of Medicine (Approval # 202104138). Consent: Inclusion criteria included males and females over 18 years of age, health care provider-documented PAD syndrome including common variable immunodeficiency (CVID), specific antibody deficiency, or hypogammaglobulinemia, and the ability to give informed consent.

   Sex as a biological variable

   Inclusion criteria included males and females over 18 years of age, health care provider-documented PAD syndrome including common variable immunodeficiency (CVID), specific antibody deficiency, or hypogammaglobulinemia, and the ability to give …

   SciScore for 10.1101/2022.01.26.22269848: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	IRB: Patients and samples: The study was approved by the Institutional Review Board of Washington University School of Medicine (Approval # 202104138). Consent: Inclusion criteria included males and females over 18 years of age, health care provider-documented PAD syndrome including common variable immunodeficiency (CVID), specific antibody deficiency, or hypogammaglobulinemia, and the ability to give informed consent.
   Sex as a biological variable	Inclusion criteria included males and females over 18 years of age, health care provider-documented PAD syndrome including common variable immunodeficiency (CVID), specific antibody deficiency, or hypogammaglobulinemia, and the ability to give informed consent.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   Exclusion criteria included participation in an investigational study of SARS-CoV-2 vaccines within the past year, history of HIV infection, an active cancer diagnosis, treatment with immunosuppressive medications, history of hematologic malignancy, treatment with anti-CD20 monoclonal antibody, receipt of live-attenuated vaccine within 30 days or any inactivated vaccine within 14 days of SARS-CoV-2 vaccination, blood or blood product donation within 30 days prior to study vaccination, and planned blood donation at any time during or 30 days after the duration of subject study participation.	anti-CD20 suggested: None
   Of the 30 subjects, 9 were diagnosed with a prior SARS-CoV-2 infection with a positive nasal swab RT-PCR test, and one received treatment with an anti-SARS-CoV-2 monoclonal antibody (bamlanivimab) 90 days prior to study enrollment.	anti-SARS-CoV-2 suggested: None
   Unbound antibodies were washed away, and antigen-bound antibodies were detected by using a PE-coupled detection antibody for each subclass and isotype (IgG1, IgG2, IgG3, IgA1, and IgM; Southern Biotech), and FcγRs were fluorescently labeled with PE before addition to immune complexes (FcγR2a, FcγR2b, FcγR3a, FcγR2b; Duke Protein Production facility).	antigen-bound suggested: None IgG1 suggested: None IgG2, IgG3 suggested: None IgA1 suggested: None
   PE median fluorescent intensity (MFI) is reported as a readout for antigen-specific antibody titers.	antigen-specific suggested: None
   Plates were washed and sequentially incubated with an oligoclonal pool of SARS2-2, SARS2-11, SARS2-16, SARS2-31, SARS2-38, SARS2-57, and SARS2-7148,49 anti-spike antibodies and HRP-conjugated goat anti-mouse IgG (Sigma) in PBS supplemented with 0.1% saponin and 0.1% BSA.	SARS2-57 suggested: None SARS2-7148,49 suggested: None anti-spike suggested: (Sigma-Aldrich Cat# ZMS1076, RRID:AB_2893440) anti-mouse IgG suggested: None
   Experimental Models: Cell Lines
   Sentences	Resources
   Antibody-virus complexes were added to Vero-TMPRSS2 cell monolayers in 96-well plates and incubated at 37°C for 1 h.	Vero-TMPRSS2 suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)
   Recombinant DNA
   Sentences	Resources
   SARS-CoV-2 spike and RBD protein expression: Genes encoding SARS-CoV-2 spike protein (residues 1-1213, GenBank: MN908947.3) and RBD (residues 319-514) were cloned into a pCAGGS mammalian expression vector with a C-terminal hexahistidine tag.	pCAGGS suggested: RRID:Addgene_127347)
   Software and Algorithms
   Sentences	Resources
   Quantification and statistical analysis: Statistical significance was assigned using Prism Version 9 (GraphPad) when P < 0.05.	GraphPad suggested: (GraphPad Prism, RRID:SCR_002798)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   One limitation of our study is the heterogeneity in the PAD patient cohort, which included those with CVID, hypogammaglobulinemia, or specific antibody deficiency. Although this was a limitation of the cohort available for study, we did not observe substantive differences between the patient subgroups. Instead, the most significant differences in antibody response to mRNA vaccines were between patients that had or lacked a prior history of SARS-CoV-2 infection. Many of our PAD patients who historically had poor immune responses to bacterial and other protein antigens (e.g., Streptococcus pneumoniae polysaccharides, tetanus toxoid, and diphtheria toxin) as part of their initial immune workup (Table S3) responded to mRNA vaccines. The basis for this difference remains unclear, although it could be due to the unique adjuvant properties of the lipid nanoparticle or in vitro-synthesized mRNA35-37. In comparison, although numbers in our cohort were clearly small (n = 3), we detected little to no antibody response at 35, 60 or 90 days after immunization of COVID-naive PAD patients with the Ad26.COV2.S adenoviral-vectored vaccine (Fig S3). Because PAD is a heterogeneous clinical entity, with many of the genetic defects unknown7-11, certain classes of adjuvants or antigens may overcome specific deficiencies and promote B cell responses, albeit at lower levels than healthy counterparts. Our data suggest that the mRNA platform may have utility for vaccination of PAD patients. That said,...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   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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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2022.01.26.22269848v1 on medRxiv

   Jan 28, 2022