# 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. ### 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 ### Paper search We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/). We ran this query: “What is the evidence for immune response and protection after Elasomeran vaccination?” The search returned 200 total results from Elicit. We retrieved 200 papers most relevant to the query for screening. ## 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 OR protection outcomes? - **Human Participants**: Does this study include human participants? - **Study Design**: Is this study a randomized controlled trial, cohort study, etc.? - **Sample Size**: Does this study include 10 or more participants? - **Full-Text Availability**: Is a full-text publication available for this study? - **Biological Outcomes Focus**: Does this study focus on biological outcomes? We considered all screening questions together and made a holistic judgement about whether to screen in each paper. ## Data extraction We asked a large language model to extract each data column below from each paper: - **Study Design**: Extract study design characteristics relevant to evaluating elasomeran immune response and protection evidence. - **Population Characteristics**: Extract participant characteristics that may affect elasomeran immune response and protection. - **Vaccination Details**: Extract elasomeran vaccination protocol and completion details. - **Humoral Immune Response**: Extract antibody response measures after elasomeran vaccination. - **Cellular Immune Response**: Extract T-cell and cellular immune response measures after elasomeran vaccination. - **Clinical Protection Outcomes**: Extract clinical protection effectiveness after elasomeran vaccination. - **Response Modifying Factors**: Extract factors that influenced immune response or protection after elasomeran vaccination. - **Safety and Tolerability**: Extract safety profile of elasomeran vaccination in the study population. ## 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. #### Study Summary | Study | Full text retrieved? | Study Type | Sample Size | Population | Vaccination Details | |----------------------------|----------------------|------------------------------|-------------|------------------------------|------------------------------------------------------------------------------| | K. Mancuso et al., 2021 | No | Observational prospective study | 96 | Multiple myeloma patients | BNT162b2 or mRNA-1273, 2 doses 3-4 weeks apart | | M. Provencio et al., 2021 | No | Observational cohort (SOLID substudy) | 1,976 | Lung cancer (67.6% stage IV) | Various vaccines, 2-dose series | | P. Ratajczak et al., 2023 | Yes | Meta-analysis of 8 RCTs | 135,275 | Healthy persons aged >16 | BNT162b2 and mRNA-1273, 100 μg dose | | Nina Kreuzberger et al., 2022 | No | Scoping review | 318 studies, >5 million participants | Immunocompromised populations | Various vaccines including mRNA-1273 | | Narcis-George Manolache et al., 2021 | Yes | Observational cohort | 231 | Rheumatic diseases | AZD1222, BNT162b2, mRNA-1273, or JNJ-78436735 | | V. Pozdnyakova et al., 2021 | Yes | Observational cohort (vaccine registry) | 353 | Inflammatory bowel disease | mRNA-1273, BNT162b2, or Ad26.CoV2.S | | S. Ehmsen et al., 2021 | Yes | Observational cohort | 524 | Solid (38%) and hematologic (62%) cancer | 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 (HM and SM) | Various vaccines including mRNA-1273 | | A. Jain et al., 2021 | No | Observational cohort | 46 | Acute myeloid leukemia and myelodysplastic syndrome | mRNA-1273, 2 doses | ### 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. Breakthrough infection rates were substantially lower with elasomeran compared to placebo. Among immunocompromised populations, seropositivity rates varied considerably by underlying condition. In lung cancer patients, 95.2% achieved seropositivity two weeks after vaccination, with geometric mean titers of 655.45 BAU/mL. In rheumatic disease patients, 82% achieved optimal humoral response. Among 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 | Responders: 245.4 ± 18.8 BAU/ml | 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 at 36 days | 36 days | Not specified | | Hematologic cancer | 66% | Median 429 BAU/mL at 36 days | 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% within first month | Not specified | 1 month | Not specified | Patients with hematologic malignancies consistently demonstrated lower seropositivity rates compared to those with solid tumors. In the cancer meta-analysis, only 60% of hematologic malignancy patients achieved seropositivity. #### Antibody Durability Several studies tracked antibody persistence over time. In lung cancer patients, antibody levels were maintained at both two weeks and six months post-vaccination. However, in the broader cancer population, median titers declined significantly from 429 BAU/mL at 36 days to 139 BAU/mL at 3 months. Among initially seropositive patients, 10% converted to seronegative status by 3 months. #### Response to Multiple Doses In kidney transplant recipients, seroconversion increased progressively with additional doses. After two initial doses, 26% achieved seroconversion. A third dose improved seroconversion further. ## Cellular Immune Response Limited data on cellular immunity were available. Among cancer patients receiving mRNA vaccination, 46% exhibited positive T-cell responses. Of those with positive responses, a significant percentage mounted both CD4+ and CD8+ T-cell responses. ## Clinical Protection Outcomes Breakthrough infection data were limited. Among lung cancer patients, only 0.5% contracted SARS-CoV-2 post-vaccination. In kidney transplant recipients, some patients experienced breakthrough infections during follow-up. ## Factors Modifying Immune Response ### Cancer Treatment and Immunosuppression Specific cancer treatments substantially impacted humoral response. Disease status at vaccination and demographic factors also affected response. | Factor Category | Specific Factor | Effect on Response | Statistical Measure | |------------------|-----------------------------------|-----------------------------|---------------------------------------| | Disease Status | Complete response (MM) | Higher Ab titers | OR 2.54 (95% CI 0.93-7.56) | | Treatment | Lenalidomide maintenance (MM) | Higher Ab titers | OR 4.53 (CI 484-1233) | | Treatment | Anti-CD20 therapy | 28% seronegativity | p<0.008 | | Treatment | Chemotherapy | 25% seronegativity | p=0.02 | ## Safety and Tolerability Safety data were limited. Mild injection site pain and fatigue were reported. Some adverse events were noted, though causality was not established. ## Synthesis The evidence demonstrates substantial heterogeneity in immune responses to elasomeran vaccination, explained through several distinct mechanisms. - The apparent discrepancy between high efficacy in healthy populations and variable seropositivity in immunocompromised groups reflects distinct immune capacity margins. - Specific treatments showed the strongest negative impact on immune responses. - The progressive increase in seroconversion with additional doses indicates a dose-response relationship rather than vaccine failure. - Disease activity strongly predicted response, with patients in complete remission typically achieving better immune responses. - The superior performance of mRNA vaccines over viral vector vaccines is evident across different patient populations. ## References 1. [P. Ratajczak et al. (2023). Tozinameran (Pfizer, BioNTech) and Elasomeran (Moderna) Efficacy in COVID-19 – A Systematic Review of Randomised Controlled Trial Studies. Healthcare](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-258913836/index.html) 2. [Nina Kreuzberger et al. (2022). Immunity after COVID-19 vaccination in people with higher risk of compromised immune status: a scoping review. Cochrane Database of Systematic Reviews](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-251444264/index.html) 3. [K. Mancuso et al. (2021). High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma. Blood](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-244539565/index.html) 4. [Narcis-George Manolache et al. (2021). Attenuated anti-SARS-CoV-2 antibody response to vaccination in patients with rheumatic diseases. Journal of Infection](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-245145375/index.html)