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. Each paper was reviewed for 6 key aspects that mattered most to the research question.

Screening

We screened in sources based on their abstracts that met these criteria:

• Human Participants with Elasomeran: Does this study involve human participants who received Elasomeran (mRNA-1273)?
• Immunogenicity Endpoints: Does this study report immunogenicity endpoints or outcomes?
• Quantitative Immunogenicity Measures: Does this study report quantitative immunogenicity measures (e.g., antibody titers, neutralizing antibody levels, T-cell responses with numerical data)?
• Appropriate Study Design: Is this study a randomized controlled trial, single-arm clinical trial, observational study, systematic review, or meta-analysis?
• Clinical Study Type: Is this a clinical study involving human participants (not a preclinical, in vitro, or animal study)?
• Primary Focus on Immunogenicity: Does this study report immunogenicity outcomes as a primary or secondary endpoint (not exclusively focused on safety, efficacy, or other non-immunogenicity outcomes)?
• Adequate Sample Size: Does this study include 10 or more participants (i.e., is it not a case report or case series with fewer than 10 participants)?
• Attributable Immunogenicity Data: Can the immunogenicity data in this study be attributed specifically to Elasomeran (i.e., can the data be separated from other interventions if multiple interventions were given)?

We considered all screening questions together and made a holistic judgement about whether to screen in each paper.

Data extraction

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, while 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.

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

Seroconversion rates were consistently high for mRNA-1273, ranging from 91.7% to 100% depending on population and time point. In the IBD cohort, mRNA-1273 achieved 100% seropositivity, comparable to BNT162b2 (99%) and superior to Ad26.CoV2.S (90%). The multiple myeloma cohort showed slightly lower seroconversion (91.7%) compared to healthy controls (100%, p=0.05). In rheumatic disease patients, mRNA-1273 recipients achieved 81% seropositivity at 4 months.

Antibody Titers

Antibody titers showed substantial variation across populations and time points. In IBD patients, mRNA-1273 produced log10 titers of 4.20 at week 2, declining to 3.72 by week 8. Multiple myeloma patients achieved median titers of 435 U/ml at 1 month, significantly lower than healthy controls (1040.5 U/ml, p=0.008). Szebeni et al. reported that mRNA-1273 achieved higher antibody levels at 4 months compared to BBIBP-CorV or AZD1222 (p=0.0107).

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. In multiple myeloma, patients receiving proteasome inhibitors had median antibody titers compared to higher levels in other patients.

Disease Status Effects

Disease control significantly influenced antibody production. In multiple myeloma, patients achieving complete response (≥CR) had significantly higher antibody titers compared to those with <CR.

Treatment-Specific Factors

Certain therapeutic interventions enhanced immunogenicity. Multiple myeloma patients who received autologous stem-cell transplantation had higher median antibody titers compared to non-transplanted patients.

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.

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.