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, and antibody levels demonstrated temporal decay across all populations from peak responses to 4-12 month follow-up.

Methods

We analyzed 4 sources from an initial pool of 200, using 8 screening criteria.

• 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.

• Papers screened out: 196

• Papers included for extraction: 4

Characteristics of Included Studies

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. Cellular immunity assessment varied by study. The Siemens assay showed good correlation with virus neutralization titers (r = 0.84).

Seropositivity thresholds were defined as IgG anti-Spike RBD ≥0.80 U/ml in the Mancuso study and ≥0 AU/ml in the Pozdnyakova study. Szebeni et al. used a diagnostic cut-off of 400 reactive cells per 10^6 parental population for T-cell 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. 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. In IBD patients, receipt of immune-modifying therapies (biologics, JAK inhibitors, immunomodulators, corticosteroids) was independently associated with lower antibody titers (β=-0.308, 95% CI -0.52 to -0.10, p=0.004). In multiple myeloma, patients receiving proteasome inhibitors had median antibody titers of 156 U/ml compared to higher levels in other patients (p=0.003).

Disease Status Effects

Disease control significantly influenced antibody production. In multiple myeloma, patients achieving complete response (≥CR) had median antibody titers of 1242 U/ml versus 221.5 U/ml in those with <CR (p<0.001).

Temporal Dynamics

Antibody levels demonstrated durability over time, though with gradual decay. In IBD patients, log10 antibody titers decreased from 4.20 at week 2 to 3.72 at week 8. Multivariable analysis at week 8 showed that longer duration between vaccine completion and blood sampling was independently associated with lower titers (β=-0.009, 95% CI -0.02 to -0.001, p=0.032).

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, immunosuppressive regimen, and disease control status. The substantial variations in response are attributable to disease activity and treatment responses, characteristics of immunosuppressive therapies, and the distinct immunogenicity profiles associated with different vaccine platforms.

References

[1] V. Pozdnyakova et al. (2021). Decreased Antibody Responses to Ad26.COV2.S Relative to SARS-CoV-2 mRNA Vaccines in Patients With Inflammatory Bowel Disease. Gastroenterology

[2] K. Mancuso et al. (2021). High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma and Relationship with Disease Status/Line of Therapy. Blood

[3] G. Szebeni et al. (2022). Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity. Frontiers in Immunology

[4] M. Jiménez et al. (2021). Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies. Blood Advances.