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 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. 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

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.

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.

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
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
3. K. Mancuso et al. (2021). High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma. Blood
4. Narcis-George Manolache et al. (2021). Attenuated anti-SARS-CoV-2 antibody response to vaccination in patients with rheumatic diseases. Journal of Infection