# 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
- n = 10
## 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.
### 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 | Full text retrieved? | Study Type | Sample Size | Population | Vaccination Details |
|-------------------------------------------------------------------------|--------------------|---------------------------------|-------------------|-------------------------------------------|------------------------------------------------------------|
| K. Mancuso et al., 2021 | No | Observational prospective study | 96 MM patients | Multiple myeloma patients | BNT162b2 or mRNA-1273, 2 doses 3-4 weeks apart |
| M. Provencio et al., 2021 | No | Observational cohort (SOLID) | 1,976 lung cancer patients | Lung cancer (67.6% stage IV) | Various vaccines, 2-dose series |
| P. Ratajczak et al., 2023 | Yes | Meta-analysis of 8 RCTs | 135,275 total participants | 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 IMID patients | Rheumatic diseases | AZD1222, BNT162b2, mRNA-1273, or JNJ-78436735 |
| V. Pozdnyakova et al., 2021 | Yes | Observational cohort (vaccine registry) | 353 IBD patients | Inflammatory bowel disease | mRNA-1273, BNT162b2, or Ad26.CoV2.S |
| S. Ehmsen et al., 2021 | Yes | Observational cohort | 524 cancer patients | Solid (38%) and hematologic (62%) cancer | mRNA vaccines, 2 doses |
| M. Seija et al., 2022 | Yes | Multicenter prospective observational | 109 kidney transplant recipients | 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 | Cancer patients (HM and SM) | Various vaccines including mRNA-1273 |
| A. Jain et al., 2021 | No | Observational cohort | 46 patients (30 AML, 16 MDS) | Acute myeloid leukemia and myelodysplastic syndrome | mRNA-1273, 2 doses |
The studies predominantly enrolled immunocompromised populations, including patients with hematologic malignancies, solid tumors, transplant recipients, and autoimmune diseases. Most patients in cancer studies were receiving active treatment at vaccination. The median age ranged from 51 years in IBD patients to 68 years in AML/MDS patients. One meta-analysis focused exclusively on healthy populations over 16 years.
## 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.
| 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 (95% CI 593.5-723.8) | 2 weeks | Chemiluminescent microparticle immunoassay |
| Rheumatic diseases | 82% optimal response | Responders: 245.4 ± 18.8 BAU/ml
Non-responders: 70.7 ± 44.9 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 (range 0.4-2500) | 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)
70.6% (homologous)| 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 versus 94% of solid malignancy patients. Similarly, in the Ehmsen study, solid cancer patients showed 93% seropositivity compared to 66% in hematologic cancer patients.
### 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, including 5 with solid cancer and 19 with hematologic cancer. An additional 24% of patients with borderline levels at 36 days became seronegative 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 by an additional 31.2%, resulting in final rates of 71.7% for the heterologous scheme (2 CoronaVac + 2 BNT162b2) and 70.6% for the homologous scheme (3 BNT162b2). Similarly, in AML/MDS patients, seropositivity increased from 69.6% after one dose to 95.7% after two doses, with mean antibody titers rising dramatically from 315 to 3806.5.
## Cellular Immune Response
Limited data on cellular immunity were available. Among cancer patients receiving mRNA vaccination, 46% of solid cancer patients and 45% of hematologic cancer patients exhibited positive T-cell responses. Of those with positive responses, 76% of solid cancer patients and 81% of hematologic cancer patients mounted both CD4+ and CD8+ T-cell responses, while 23% and 18% respectively elicited only CD8+ responses. Notably, 76% of seronegative patients did not elicit a T-cell response. The cancer meta-analysis reported an overall cellular response rate of 61% (95% CI 44-76%), with 59% in hematologic malignancies and 68% in solid malignancies.
Multiple myeloma patients underwent IGRA testing for SARS-CoV-2 specific IFN-γ T-cell response at 3 and 12 months after the second dose, though specific results were not reported in the available abstract.
## Clinical Protection Outcomes
Breakthrough infection data were limited. Among lung cancer patients, only 0.5% (10 patients) contracted SARS-CoV-2 within a median of 19 days (IQR 5-76) after full vaccination. In kidney transplant recipients, 10 patients experienced breakthrough infections during a 5-month follow-up, with no deaths reported.
Performance status and comorbidities significantly influenced clinical protection. Lung cancer patients with performance status ≥2 had higher odds of being seronegative (OR 4.38, 95% CI 2.24-8.55, p<0.001), as did those with comorbidities (OR 3.43, 95% CI 1.32-8.87, p=0.011).
## 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.
| 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) |
| Disease Status | Progressive disease (hematologic) | Associated with seronegativity | Significant association |
| Treatment | Lenalidomide maintenance (MM) | Higher Ab titers (median 1681.2 U/ml) | OR 4.53 (CI 484-1233) |
| Treatment | Anti-CD38 antibodies (MM) | Lower Ab titers (median 265 U/ml) | p<0.001 |
| Treatment | Proteasome inhibitors (MM) | Lower Ab titers (median 156 U/ml) | p=0.003 |
| Treatment | Anti-CD20 therapy | 28% seronegativity | p<0.008 |
| Treatment | BTK inhibitors | 11% seronegativity | p=0.002 |
| Treatment | Chemotherapy | 25% seronegativity | p=0.02 |
| Treatment | Steroids (prednisolone) | Associated with seronegativity | p=0.005 |
| Treatment | Mycophenolate (KTR) | Lower seroconversion | Significant association |
### Disease-Specific Response Patterns
Among hematologic malignancies, specific diagnoses showed markedly different seropositive rates. Only 11% of mantle cell lymphoma patients achieved seropositivity, while 55% of CLL/SLL patients and 62% of follicular lymphoma patients became seropositive. Higher rates were observed in marginal zone lymphoma (72%), multiple myeloma (80%), and diffuse large B cell lymphoma (85%).
Disease remission status also influenced response. In multiple myeloma, patients with very good partial response or better had median antibody titers of 1242 U/ml compared to 221.5 U/ml in those with lesser responses. Similarly, hematologic cancer patients in remission were more likely to be seropositive than those with progressive disease.
### Vaccine-Specific Differences
In rheumatic disease patients, those receiving mRNA vaccines showed 85% optimal humoral response versus only 69% with viral vector vaccines. Multivariate analysis confirmed that vaccine type remained significantly associated with response when controlling for age, treatment, and time between vaccination and antibody measurement.
Among IBD patients, those receiving mRNA-1273 or BNT162b2 showed substantially higher antibody levels at both 2 and 8 weeks compared to Ad26.CoV2.S recipients. At 2 weeks, log10 antibody levels were 4.20 for mRNA-1273, 3.92 for BNT162b2, and only 1.96 for Ad26.CoV2.S. These differences persisted at 8 weeks (3.72, 3.41, and 2.65 respectively). Multivariate analysis demonstrated that both mRNA-1273 and BNT162b2 independently predicted higher antibody levels at week 2 (β 2.24 and 1.96 respectively) and week 8 (β 1.08 and 0.77 respectively).
## Safety and Tolerability
Safety data were limited across studies. In AML/MDS patients, mild injection site pain, fatigue, headache, and arm swelling were the most common adverse events. Two AML patients experienced disease relapse post-vaccination, though no direct link to vaccination was established. The meta-analysis of RCTs found that BNT162b2 and mRNA-1273 administration was associated with higher proportions of adverse events compared to placebo (RR 2.14 [1.99, 2.29], p<0.00001), though serious adverse events showed no significant difference (RR 0.98 [0.89, 1.08], p=0.68). Identified serious adverse events potentially related to vaccination included hypersensitivity reactions, dermal filler reactions, Bell’s palsy, thromboembolism, and pericarditis, though specific rates were not provided.
Among lung cancer patients, the study concluded that patients could "safely achieve a strong immune response", though specific adverse event data were not detailed. In kidney transplant recipients, during 5-month follow-up, two rejection episodes and one IgA nephropathy recurrence occurred, though causality with vaccination was not established.
## Synthesis
The evidence demonstrates substantial heterogeneity in immune responses to elasomeran vaccination, which can be explained through several distinct mechanisms rather than representing contradictory findings.
### Population-Specific Response Margins
The apparent discrepancy between high efficacy in healthy populations (RR 0.08 for preventing COVID-19) and variable seropositivity in immunocompromised groups reflects distinct immune capacity margins. Lung cancer patients achieved 95.2% seropositivity, multiple myeloma patients 91.7%, and rheumatic disease patients 82%, while hematologic malignancy patients showed only 60-66% seropositivity. These differences align with underlying B-cell function: solid tumors primarily affect tissue architecture rather than immune cell production, while hematologic malignancies directly impair lymphocyte development and antibody production. The finding that patients with B-cell malignancies (mantle cell lymphoma 11%, CLL/SLL 55%) showed the lowest response rates supports this mechanistic explanation.
### Treatment-Dependent Immunosuppression Hierarchy
The variable impact of immunosuppressive treatments follows predictable patterns based on their mechanisms of action. B-cell-depleting therapies showed the strongest negative impact: anti-CD20 therapy associated with 28% seronegativity, while anti-CD38 antibodies in multiple myeloma yielded median titers of only 265 U/ml. These agents directly eliminate antibody-producing cells, explaining the profound suppression. In contrast, agents preserving B-cell populations but modulating their function showed intermediate effects: BTK inhibitors associated with 11% seronegativity, and mycophenolate in transplant recipients reduced but did not eliminate response. Treatments enhancing immune function showed opposite effects: patients on immunotherapy had decreased seronegativity odds (OR 0.25), while those receiving lenalidomide maintenance achieved median titers of 1681.2 U/ml, likely through immunomodulatory effects that enhance T-cell help for B-cell responses.
### Temporal Dynamics and Dose-Response Relationships
The progressive increase in seroconversion with additional doses demonstrates a dose-response relationship rather than vaccine failure. Kidney transplant recipients improved from 26% after two doses to 71.7% after four doses, while AML/MDS patients increased from 69.6% to 95.7% after a second dose. This pattern suggests immunocompromised patients require greater antigenic stimulus to overcome suppression. The observed antibody decay (median titers declining from 429 to 139 BAU/mL between 36 days and 3 months) with 10% of initially seropositive patients converting to seronegative status indicates that maintenance of response may require more frequent boosting in these populations than in healthy individuals.
### Disease State as Immune Capacity Indicator
Disease activity strongly predicted response, with patients in complete remission achieving median titers of 1242 U/ml versus 221.5 U/ml in those with lesser responses. This correlation likely reflects underlying immune competence: patients achieving disease control typically have better preserved immune function and lower disease burden. Progressive disease associated with higher seronegativity may result from both disease-related immune dysfunction and typically more intensive immunosuppressive treatment requirements.
### Platform-Specific Immunogenicity
The superior performance of mRNA vaccines over viral vector vaccines in rheumatic disease patients (85% vs 69% optimal response) and consistently higher antibody levels with mRNA-1273 and BNT162b2 versus Ad26.CoV-2.S in IBD patients (log10 values 4.20 and 3.92 vs 1.96 at 2 weeks) likely reflects fundamental differences in antigen presentation kinetics and magnitude. mRNA vaccines enable prolonged in situ antigen production, potentially compensating for impaired immune surveillance in immunocompromised patients. This advantage persisted even when controlling for immunosuppression status, suggesting platform-intrinsic rather than population-dependent differences.