Immune Response to Elasomeran Vaccination

What is the evidence for immune response and protection after Elasomeran vaccination?

Evidence demonstrates that elasomeran vaccination induces robust immune responses and clinical protection across most populations, though patients with hematologic malignancies and those on B-cell-depleting therapies show attenuated responses that improve with additional doses.

Abstract

Elasomeran vaccination demonstrates high efficacy in healthy populations, with risk ratios of 0.08 for preventing COVID-19 and breakthrough infection rates of 0.23%. In immunocompromised populations, humoral responses vary substantially by underlying condition: seropositivity rates reach 95.2% in lung cancer patients, 91.7% in multiple myeloma, and 82% in rheumatic disease patients, but only 60-66% in hematologic malignancies. Cellular immune responses occur in approximately 46% of cancer patients, with most mounting both CD4+ and CD8+ T-cell responses. Antibody titers decline substantially over time, decreasing from median 429 to 139 BAU/mL between 36 days and 3 months post-vaccination, with 10% of initially seropositive patients converting to seronegative status. Response heterogeneity is explained by specific mechanisms: B-cell-depleting therapies (anti-CD20, anti-CD38) profoundly suppress antibody production, disease remission predicts superior response (median titers 1242 vs 221.5 U/ml), and mRNA vaccines induce higher antibody levels than viral vector vaccines. Additional doses substantially improve seroconversion in immunocompromised patients, increasing rates from 26% after two doses to 71.7% after four doses in kidney transplant recipients and from 69.6% to 95.7% after a second dose in AML/MDS patients. Clinical protection remains robust in most immunocompromised populations, with breakthrough infection rates of only 0.5% in lung cancer patients. The evidence indicates that while elasomeran induces strong immune responses in most populations, patients with hematologic malignancies and those receiving B-cell-depleting therapies require additional doses and may need more frequent boosting to maintain protective immunity.

Methods

We analyzed 10 sources from an initial pool of 200, using 7 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

Paper Search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex. We ran this query: “What is the evidence for immune response and protection after Elasomeran vaccination?” The search returned 200 total results from Elicit.

Screening

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

• Elasomeran Vaccination: Does this study involve participants who received Elasomeran (mRNA-1273) vaccination?
• Relevant Outcomes: Does this study measure immune response outcomes (e.g., antibody titers, neutralizing antibodies, T-cell responses, B-cell responses) OR protection outcomes (e.g., vaccine efficacy, vaccine effectiveness, prevention of infection, hospitalization, severe disease, or death)?
• Human Participants: Does this study include human participants (not exclusively in vitro or animal studies)?
• Study Design: Is this study a randomized controlled trial, cohort study, case-control study, cross-sectional study, systematic review, or meta-analysis?
• 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)?
• Full-Text Availability: Is a full-text publication available for this study (i.e., is it NOT solely a conference abstract without full-text)?
• Biological Outcomes Focus: Does this study focus on biological outcomes rather than exclusively on safety/reactogenicity, vaccine hesitancy, acceptance, or logistical aspects without measuring immune response or protection outcomes?

Data Extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

Results

Characteristics of Included Studies

Ten studies met the inclusion criteria, comprising two meta-analyses, one scoping review, and seven primary observational studies. Full text was available for six studies, while four studies were available only as abstracts.

Humoral Immune Response

Seropositivity Rates in Healthy vs Immunocompromised Populations

In the healthy population meta-analysis, both BNT162b2 and mRNA-1273 demonstrated high efficacy in preventing COVID-19 compared to placebo (RR 0.08 [0.07, 0.09], p<0.00001). Breakthrough infection rates were substantially lower with elasomeran (0.23%) compared to placebo (3.29%).

Among immunocompromised populations, seropositivity rates varied considerably by underlying condition. In lung cancer patients, 95.2% achieved seropositivity two weeks after vaccination (threshold 7.1 BAU/mL), with geometric mean titers of 655.45 BAU/mL (95% CI 593.5-723.8). In rheumatic disease patients, 82% achieved optimal humoral response (anti-RBD Ab >141 BAU/ml). Among IBD patients, mRNA-1273 recipients showed 100% seropositivity at 2 weeks with log10 antibody levels of 4.20.

Factors Modifying Immune Response

Cancer Treatment and Immunosuppression

Specific cancer treatments substantially impacted humoral response. In multiple myeloma patients, those receiving proteasome inhibitors had median antibody titers of 156 U/ml, while those on anti-CD38 monoclonal antibodies had median titers of 265 U/ml, both lower than other treatment groups. Conversely, patients receiving lenalidomide maintenance had median titers of 1681.2 U/ml, and those who had undergone autologous stem cell transplantation showed median titers of 1042 U/ml.

In hematologic cancer patients, anti-CD20 therapy was associated with seronegativity in 28% of patients, BTK inhibitor therapy in 11%, and chemotherapy in 25%. Steroid use (prednisolone >10mg) was significantly associated with seronegativity. Multivariate analysis confirmed significant associations between seronegative rates and steroid use, stem cell transplantation, type of cancer therapies, and cancer diagnosis.