Elicit: Impact of Variants on Elasomeran Mechanism
Impact of Variants on Elasomeran Mechanism
How do updated formulations (variants of concern) affect the mechanism of Elasomeran?
Abstract
Updated mRNA-1273 formulations targeting SARS-CoV-2 variants of concern alter the immune response mechanism through differential neutralizing antibody profiles while maintaining the platform’s core immunological pathways. Monovalent variant-specific vaccines (mRNA-1273.351 targeting B.1.351, mRNA-1273.529 targeting BA.1) demonstrated superior neutralizing antibody responses against their target variants, with geometric mean ratios of 1.67-1.77 for BA.1 formulations and twofold improvements for B.1.351 formulations, but showed reduced cross-reactivity against ancestral strains with fourfold lower neutralization against WA1/2020 D614G. Bivalent formulations (mRNA-1273.211, mRNA-1273.214) balanced this trade-off by maintaining or improving ancestral strain neutralization (GMR 1.11 against D614G for BA.1-bivalent) while achieving GMT ratios ≥1 against all variants of concern tested. All updated formulations induced robust anamnestic B cell memory responses when used as boosters, with variant-modified boosters showing 34.9-61.6 fold increases in neutralization against target variants, restoring immunity that had waned 6-7 fold against wild-type and 24-69 fold against variants over 6 months. Cellular immune mechanisms, including CD4+ and CD8+ T cell responses measured in preclinical models, showed similar activation patterns to the original vaccine, with effector T cell expansion but not effector-memory phenotypes and waning within 6 months. However, longitudinal studies revealed progressive viral escape from updated vaccine-induced immunity, with newer variants continuing to evade even XBB.1.5-updated formulations, indicating that antigenic drift outpaces the vaccine update cycle despite mechanistic improvements in neutralizing breadth and depth.
Methods
We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 8 key aspects relevant 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: “How do updated formulations (variants of concern) affect the mechanism of Elasomeran?”
The search returned 200 total results from Elicit. We screened in sources based on their abstracts that met several criteria, including vaccine type, mechanistic outcomes, study design, and study rigor.
Results
Characteristics of Included Studies
The systematic review identified 10 sources examining updated mRNA-1273 (Elasomeran) formulations targeting SARS-CoV-2 variants of concern.
Study Overview
| Study | Full text retrieved? | Updated formulation(s) | Study type | Population | Primary focus |
|---|---|---|---|---|---|
| Ivan T Lee et al., 2023 | No | BA.1-monovalent (mRNA-1273.529), BA.1-bivalent (mRNA-1273.214) | Phase 3 RCT | Adults ≥16 years, UK | 3-month safety and immunogenicity of BA.1-containing boosters |
| Kai Wu et al., 2021 | No | mRNA-1273.351, mRNA-1273.211 | Preclinical (mice) | Mice | Variant vaccine neutralization as primary or booster series |
| A. Choi et al., 2021 | Yes | mRNA-1273.351, mRNA-1273.211 | Phase 2a clinical trial | Healthy adults (mean ages 47.5-63.8 years), US | Safety and immunogenicity of variant-modified boosters |
| K. Wu et al., 2021 | Yes | mRNA-1273.351, mRNA-1273.211 | Phase 2 clinical trial | Adults ≥18 years, US | Preliminary safety and immunogenicity of variant vaccine booster |
| M. Koch et al., 2021 | No | mRNA-1273.351, mRNA-1273.211 | Preclinical (mice) | Mice | Variant vaccine neutralization and cross-protection |
| Baoling Ying et al., 2021 | Yes | mRNA-1273.351, mRNA-1273.211 | Preclinical (mice) | 129S2 and K18-hACE2 mice | Protective activity against ancestral and variant strains |
| Baoling Ying et al., 2021a | Yes | mRNA-1273.351 | Preclinical (mice) | 129S2 and K18-hACE2 mice | Protection against variants with suboptimal immunity |
| M. Echaide et al., 2023 | Yes | Bivalent vaccines (Comirnaty, Spikevax) targeting BA.4-5 Omicron | Review | Multiple populations including elderly, pediatric, immunocompromised | Advantages and limitations of mRNA vaccines against variants |
| A. Roederer et al., 2024 | Yes | XBB.1.5 monovalent booster | Prospective cohort | Adults (median 33) and elderly (median 72), COVID-naive | Evolution of viral escape from vaccine immunity |
| A. Pegu et al., 2021 | No | None (durability study of original mRNA-1273) | Clinical immunogenicity study | Vaccine recipients | Durability of antibodies against variants |
Immunological Mechanisms Assessed
Studies evaluated multiple immunological mechanisms to characterize how updated formulations affect the immune response to SARS-CoV-2 variants.
- Neutralizing antibodies: Pseudovirus neutralization assays (lentivirus-based, VSV-based); live virus focus-reduction neutralization test (FRNT)
- Binding antibodies: ELISA measuring IgG against recombinant spike proteins
- T cell responses: CD4+ and CD8+ T cell responses measured via peptide stimulation and interferon-γ production
- Cellular immune responses: Anamnestic responses to boosting; durability measured at multiple time points
Variant Testing Panels
Updated formulations were tested against comprehensive panels of SARS-CoV-2 variants to assess both homologous and cross-reactive immune responses.
| Study | Ancestral strain | Variants of concern tested | Variant formulation designed for | Cross-reactivity assessed |
|---|---|---|---|---|
| Ivan T Lee et al., 2023 | D614G | BA.1 Omicron | BA.1 | Yes (D614G) |
| Kai Wu et al., 2021 | Wild-type | B.1.351 (Beta) | B.1.351 | Yes (broad cross-variant) |
| A. Choi et al., 2021 | D614G | B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) | B.1.351 | Yes (multiple VOCs) |
Effects of Updated Formulations on Neutralizing Antibody Responses
Superiority Against Homologous Variants
Updated formulations demonstrated superior neutralizing antibody responses against their target variants compared to the original mRNA-1273 vaccine.
| Study | Updated formulation | Target variant | Comparison to original mRNA-1273 | GMR or fold-change | Statistical significance |
|---|---|---|---|---|---|
| Ivan T Lee et al., 2023 | BA.1-monovalent | BA.1 Omicron | Superior at Month 3 | GMR 1.77 (96% CI 1.55-2.02) | Yes |
| A. Choi et al., 2021 | mRNA-1273.351 (50 μg) | B.1.351 | Numerically greater titers | 34.9-fold increase | Not confirmed |
| Baoling Ying et al., 2021 | mRNA-1273.351 | B.1.351 | Twofold higher GMTs | Twofold vs mRNA-1273 | Superiority noted |
Booster Effects on Waning Immunity
Booster doses with updated formulations restored and enhanced neutralizing antibody titers that had declined over time.
| Study | Pre-booster titers | Post-booster titers | Magnitude of increase | Timing |
|---|---|---|---|---|
| A. Choi et al., 2021 | Waned significantly vs peak at Month 1 | mRNA-1273.211: 61.6-fold vs B.1.351 | Significant (P<0.0001) | ~6 months post-primary |
Conclusions
The findings reveal patterns in how updated mRNA-1273 formulations alter immunological mechanisms. Monovalent variant-specific vaccines showed superior neutralization against their target variants but reduced neutralization against ancestral strains, while bivalent formulations maintained broad cross-variant protection. Emergent variants demonstrate that antigenic drift is happening faster than the vaccine update cycle. Updated boosters significantly restore waning immunity, affirming the importance of memory B cells in responding to evolving strains.