Key Immunogenicity Endpoints in Elasomeran Studies

What are the key immunogenicity endpoints reported for Elasomeran clinical studies?

The key immunogenicity endpoints for Elasomeran clinical studies were anti-Spike IgG antibody levels and seroconversion rates for humoral immunity (primary endpoints) and SARS-CoV-2 specific T-cell responses for cellular immunity (secondary endpoints), assessed from 2 weeks to 12 months post-vaccination.

Abstract

Four observational studies evaluated mRNA-1273 (Elasomeran) immunogenicity in immunocompromised populations including inflammatory bowel disease, multiple myeloma, hematologic malignancies, and autoimmune rheumatic diseases. The primary immunogenicity endpoints were humoral responses measured by anti-Spike IgG antibodies targeting the receptor binding domain using electrochemiluminescence assays, with seropositivity thresholds defined as ≥0.80 U/ml or ≥0 AU/ml. Secondary endpoints included cellular immunity assessed through SARS-CoV-2 specific T-cell responses measured by interferon-gamma release assays and cytokine production (TNF-α, IFN-γ). Assessment timepoints ranged from 2 weeks to 12 months post-vaccination. Seroconversion rates were consistently high across populations (91.7-100%), though absolute antibody titers varied substantially. Titers in multiple myeloma patients (median 435 U/ml) were significantly lower than healthy controls (1040.5 U/ml, p=0.008), and mRNA-1273 produced higher titers than Ad26.CoV2.S in IBD patients at both week 2 (log10 4.20 vs 1.96) and week 8 (3.72 vs 2.65, p<0.001). Immunosuppressive therapies, particularly anti-CD20 and anti-CD38 antibodies, substantially reduced humoral responses, while disease remission status, autologous stem-cell transplantation, and lenalidomide maintenance independently predicted higher antibody titers. Notably, cellular responses were preserved in patients receiving anti-CD20 therapy despite impaired humoral immunity.

Methods

We analyzed 4 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 6 key aspects that mattered most to the research question. More on methods

Records from Elicit search

• n = 200
• Papers screened using: Human Participants with Elasomeran, Immunogenicity Endpoints, Quantitative Immunogenicity Measures, Appropriate Study Design, Clinical Study Type, Primary Focus on Immunogenicity, Adequate Sample Size, Attributable Immunogenicity Data
• n = 200
• Papers screened out
• n = 196
• Papers included for extraction
• n = 4

Characteristics of Included Studies

Study Overview

Four studies evaluated the immunogenicity of mRNA-1273 (Elasomeran) across diverse immunocompromised populations.

Immunogenicity Endpoints and Measurement Methods

The studies assessed both humoral and cellular immunity using standardized assays. Humoral immunity was measured through anti-Spike IgG antibodies targeting the receptor binding domain. Pozdnyakova et al. used the SARS-CoV-2 IgG-II assay from Abbott Labs, Mancuso et al. employed the Elecsys® Anti-SARS-CoV-2 ECLIA platform, and Szebeni et al. utilized the Siemens Advia Centaur XPT system with Siemens Healthineers SARS-CoV-2 IgG assay. The Siemens assay showed good correlation with virus neutralization titers (r = 0.84).

Cellular immunity assessment varied by study.

• Mancuso et al. evaluated SARS-CoV-2 specific IFNγ T cell responses using IGRA tests.
• Szebeni et al. measured T-cell responses including TNF-α and IFN-γ production by CD4+ and CD8+ T-cells using the SARS-CoV-2 T-Cell Analysis Kit from Miltenyi Biotec.
• Jiménez et al. reported preserved cellular responses in patients under anti-CD20 therapy despite impaired humoral responses.

Timing of Immunogenicity Assessment

Assessment time points varied considerably across studies. Pozdnyakova et al. measured antibody responses at three post-vaccination time points: after regimen completion (2-13 days), week 2 (14-29 days), and week 8 (42-84 days). Mancuso et al. conducted more extensive longitudinal follow-up, measuring humoral responses at 1, 3, 6, 9, and 12 months post-second dose, with cellular immunity evaluated at 3 and 12 months. The primary analysis in Mancuso’s study focused on 1 month post-vaccination (median 30 days, IQR 28-32). Szebeni et al. assessed responses at 1 and 4 months after the second dose.

Immunogenicity Results

Seroconversion Rates

Antibody Titers

Factors Influencing Immunogenicity

Impact of Immunosuppressive Medications

Immunosuppressive therapies substantially affected humoral responses across multiple studies. Immunosuppressants were associated with lower antibody titers, particularly in patients receiving B-cell depleting therapies.

Disease Status Effects

Disease control significantly influenced antibody production, with complete responders showing notably higher antibody titers compared to those with less favorable disease profiles.

Synthesis

The evidence demonstrates consistently high seroconversion rates for mRNA-1273 across diverse immunocompromised populations (91.7-100%), though absolute antibody titers varied substantially based on underlying disease and immunosuppressive regimen. Antibody levels showed temporal decay over time despite maintaining high seroconversion rates. This highlights the importance of understanding individual patient factors when assessing vaccine-induced immunity.

References

1. V. Pozdnyakova et al., 2021
2. K. Mancuso et al., 2021
3. G. Szebeni et al., 2022
4. M. Jiménez et al., 2021