# 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 significantly 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

## 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 | Study Type | Sample Size | Population | Vaccination Details |
| --- | --- | --- | --- | --- |
| K. Mancuso et al., 2021 | Observational prospective study | 96 | Multiple myeloma patients | BNT162b2 or mRNA-1273, 2 doses 3-4 weeks apart |
| M. Provencio et al., 2021 | Observational cohort (SOLID substudy) | 1,976 | Lung cancer patients | Various vaccines, 2-dose series |
| P. Ratajczak et al., 2023 | Meta-analysis of 8 RCTs | 135,275 | Healthy persons aged >16 | BNT162b2 and mRNA-1273, 100 μg dose |
| Nina Kreuzberger et al., 2022 | Scoping review | 318 studies, >5 million | Immunocompromised populations | Various vaccines including mRNA-1273 |
| Narcis-George Manolache et al., 2021 | Observational cohort | 231 | Rheumatic diseases | AZD1222, BNT162b2, mRNA-1273, or JNJ-78436735 |
| V. Pozdnyakova et al., 2021 | Observational cohort (vaccine registry) | 353 | Inflammatory bowel disease | mRNA-1273, BNT162b2, or Ad26.CoV2.S |
| S. Ehmsen et al., 2021 | Observational cohort | 524 | Cancer (solid and hematologic) | mRNA vaccines, 2 doses |
| M. Seija et al., 2022 | Multicenter prospective observational | 109 | Kidney transplant recipients | Heterologous (4 doses) or homologous (3 doses) schemes |
| D. Martins-Branco et al., 2022 | Meta-analysis of 89 records | 30,183 | Cancer patients (HM and SM) | Various vaccines including mRNA-1273 |
| A. Jain et al., 2021 | Observational cohort | 46 | 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

The healthy population meta-analysis showed 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).

| 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 |

Patients with hematologic malignancies consistently demonstrated lower seropositivity rates compared to those with solid tumors.

### 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.

### 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.

### 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 after full vaccination. In kidney transplant recipients, 10 patients experienced breakthrough infections during a 5-month follow-up, with no deaths reported.

## Factors Modifying Immune Response

### Cancer Treatment and Immunosuppression

Specific cancer treatments substantially impacted humoral response. In multiple myeloma patients, those receiving proteasome inhibitors had lower median antibody titers. Conversely, patients receiving lenalidomide maintenance had higher median titers.

| 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 (median 1681.2 U/ml) | OR 4.53 (CI 484-1233) |
| Treatment | Anti-CD20 therapy | 28% seronegativity | p<0.008 |
| Treatment | Steroids (prednisolone) | Associated with seronegativity | p=0.005 |

### Disease-Specific Response Patterns

Among hematologic malignancies, specific diagnoses showed markedly different seropositive rates. Disease remission status also influenced response.

### Vaccine-Specific Differences

In rheumatic disease patients, those receiving mRNA vaccines showed higher optimal humoral response compared to viral vector vaccines.

## Safety and Tolerability

Safety data were limited across studies. Common adverse events included mild injection site pain, fatigue, headache, and arm swelling. Serious adverse events potentially related to vaccination included hypersensitivity reactions, though specific rates were not provided.

## 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 reflect distinct immune capacity margins.

## References

1. [P. Ratajczak et al., 2023](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-258913836/index.html)
2. [Nina Kreuzberger et al., 2022](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-251444264/index.html)
3. [K. Mancuso et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-244539565/index.html)
4. [Narcis-George Manolache et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-245145375/index.html)
5. [V. Pozdnyakova et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-236991786/index.html)
6. [S. Ehmsen et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-236435578/index.html)
7. [M. Seija et al., 2022](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-248723912/index.html)
8. [D. Martins-Branco et al., 2022](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-250927780/index.html)
9. [A. Jain et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-244644615/index.html)
10. [M. Provencio et al., 2021](/content/review/5a422cef-207b-4a82-9716-8e71ec9bbd39/source/ss-245453264/index.html)