# 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. ### Records from Elicit search n = 200 ### Papers screened using: - Elasomeran Vaccination - Relevant Outcomes - Human Participants - Study Design - Sample Size - Full-Text Availability - Biological Outcomes Focus n = 200 ### Papers screened out n = 190 ### Papers included for extraction n = 10 ## Paper search We performed a semantic search across over 138 million academic papers from the Elicit search engine. 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**: Study involves participants who received Elasomeran (mRNA-1273) vaccination? - **Relevant Outcomes**: Study measures immune response outcomes or protection outcomes? - **Human Participants**: Study includes human participants? - **Study Design**: Is this study a randomized controlled trial, cohort study, etc.? - **Sample Size**: Study includes 10 or more participants? - **Full-Text Availability**: Is a full-text publication available for this study? - **Biological Outcomes Focus**: Study focuses on biological outcomes? ## Data extraction We extracted data across various columns relevant to evaluating elasomeran immune response and protection evidence including: - **Study Design**: Type, sample size for elasomeran recipients, follow-up duration, risk of bias indicators. - **Population Characteristics**: Age distribution, immunocompromising conditions, prior COVID-19 infection status, and comorbidities. - **Vaccination Details**: Dose administered, vaccination schedule, number of doses received, and time from last dose to outcome measurement. - **Humoral Immune Response**: Seropositivity rates, quantitative antibody titers, and durability data. - **Cellular Immune Response**: T-cell response rates, characteristics, and cytokine production patterns. - **Clinical Protection Outcomes**: COVID-19 breakthrough infection rates, severity, and effectiveness percentages. - **Response Modifying Factors**: Specific treatments, disease status, demographic factors, and clinical associations. - **Safety and Tolerability**: Local/systemic reactions, serious adverse events, and tolerability in immunocompromised populations. ## Results ### Characteristics of Included Studies Ten studies met the inclusion criteria, comprising two meta-analyses, one scoping review, and seven primary observational studies. | Study | Full text retrieved? | Study Type | Sample Size | Population | Vaccination Details | |-------|--------------------|------------|-------------|------------|---------------------| | K. Mancuso et al., 2021 | No | Observational prospective study | 96 | MM patients | BNT162b2 or mRNA-1273, 2 doses 3-4 weeks apart | | M. Provencio et al., 2021 | No | Observational cohort | 1,976 | Lung cancer | Various vaccines, 2-dose series | | P. Ratajczak et al., 2023 | Yes | Meta-analysis of 8 RCTs | 135,275 | Healthy persons >16 | BNT162b2 and mRNA-1273, 100 μg dose | | Nina Kreuzberger et al., 2022 | No | Scoping review | 318 studies, >5 million | Immunocompromised populations | Various vaccines including mRNA-1273 | | Narcis-George Manolache et al., 2021 | Yes | Observational cohort | 231 | IMID patients | AZD1222, BNT162b2, mRNA-1273, or JNJ-78436735 | | V. Pozdnyakova et al., 2021 | Yes | Observational cohort | 353 | IBD patients | mRNA-1273, BNT162b2, or Ad26.CoV2.S | | S. Ehmsen et al., 2021 | Yes | Observational cohort | 524 | Cancer patients | mRNA vaccines, 2 doses | | M. Seija et al., 2022 | Yes | Multicenter prospective observational | 109 | Kidney transplant recipients | Heterologous (4 doses) or homologous (3 doses) schemes | | D. Martins-Branco et al., 2022 | Yes | Meta-analysis of 89 records | 30,183 | Cancer patients | Various vaccines including mRNA-1273 | | A. Jain et al., 2021 | No | Observational cohort | 46 | AML/MDS | mRNA-1273, 2 doses | ## Humoral Immune Response ### Seropositivity Rates in Healthy vs Immunocompromised Populations In healthy populations, both BNT162b2 and mRNA-1273 demonstrated high efficacy in preventing COVID-19. Breakthrough infection rates were substantially lower with elasomeran compared to placebo. Among immunocompromised populations, seropositivity rates varied considerably by underlying condition. For instance, in lung cancer patients, 95.2% achieved seropositivity two weeks after vaccination. In rheumatic disease patients, 82% achieved optimal humoral response. In IBD patients, mRNA-1273 recipients showed 100% seropositivity at 2 weeks. | Population | Seropositivity Rate | Quantitative Titers | Time Point | Assay Method | |------------|---------------------|---------------------|------------|---------------| | Healthy (meta-analysis) | High efficacy (RR 0.08) | Not specified | 14 days post-dose 2 | Not specified | | Lung cancer | 95.2% | GMT 655.45 BAU/mL | 2 weeks | Chemiluminescent microparticle immunoassay | | Rheumatic diseases | 82% optimal response | 245.4 ± 18.8 BAU/ml (responders) | Post-vaccination | Elecsys anti-SARS-CoV-2 | | IBD (mRNA-1273) | 100% | Log10: 4.20 at 2 weeks | 2 weeks | Abbott SARS-CoV-2 IgG-II | | Multiple myeloma | 91.7% | Median 435 U/ml | 1 month | ECLIA (Elecsys) | | Solid cancer | 93% | Median 429 BAU/mL | 36 days | Not specified | | Hematologic cancer | 66% | Median 429 BAU/mL | 36 days | Not specified | | AML/MDS | 95.7% after 2 doses | Mean 3806.5 after dose 2 | Day 57 | Two-step ELISA | | Kidney transplant | 71.7% (heterologous) | Higher in Seroconversion-2D group | Post-vaccination | Anti-RBD IgG assay | | Cancer meta-analysis | 80% | Not specified | 1 month | Not specified | ### Antibody Durability Several studies tracked antibody persistence over time. In lung cancer patients, antibody levels maintained at both two weeks and six months post-vaccination. Moreover, 10% of initially seropositive patients converted to seronegative status by 3 months. ### Response to Multiple Doses In kidney transplant recipients, seroconversion increased progressively with additional doses. The pattern suggests immunocompromised patients require greater antigenic stimulus to overcome suppression. ## Cellular Immune Response Limited data on cellular immunity were available. Among cancer patients, 46% of solid cancer patients and 45% of hematologic cancer patients exhibited positive T-cell responses. ## Clinical Protection Outcomes Breakthrough infection data was limited. Among lung cancer patients, only 0.5% contracted SARS-CoV-2 post-vaccination. Performance status and comorbidities significantly influenced clinical protection. ## Factors Modifying Immune Response ### Cancer Treatment and Immunosuppression Specific cancer treatments substantially impacted humoral response. For instance, patients receiving lenalidomide maintenance had higher Ab titers compared to those on anti-CD38 monoclonal antibodies. ### Disease-Specific Response Patterns Among hematologic malignancies, specific diagnoses showed markedly different seropositive rates. ### Vaccine-Specific Differences In rheumatic disease patients, those receiving mRNA vaccines exhibited a significantly higher optimal humoral response compared to those receiving viral vector vaccines. ## Safety and Tolerability Safety data were limited across studies. Mild injection site pain, fatigue, headache, and arm swelling were noted as common adverse events. The overall finding suggested BNT162b2 and mRNA-1273 administration had higher proportions of adverse events compared to placebo. ## Synthesis The evidence demonstrates substantial heterogeneity in immune responses to elasomeran vaccination, explained through several distinct mechanisms rather than representing contradictory findings.