# 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.

| 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 patients | 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 | 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 | 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 (HM and SM) | Various vaccines including mRNA-1273 |
| A. Jain et al., 2021 | No | Observational cohort | 46 | Acute myeloid leukemia and MDS | 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 (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                      |

## 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.