Antibodies, Neutralizing / Vaccines, Synthetic / Immunogenicity, Vaccine · Journal article

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

Human Vaccines & Immunotherapeutics · August 26, 2026

Promising Why this matters to you Expert discussion

Encouraging direction, but not yet definitive.

AI Summary

This phase 2 trial demonstrates that two investigational bivalent and monovalent mRNA COVID-19 vaccines (CV0701 and CV0601) induce dose-dependent neutralizing antibody responses and T-cell responses comparable to a licensed bivalent vaccine, with no serious vaccine-related adverse events. The finding is limited to immunogenicity endpoints in previously vaccinated healthy adults and requires phase 3 confirmation with clinical outcomes before informing practice.

What was studied

Randomized, multi-center, active-controlled, observer-blind phase 2 trial. Healthy adults aged ≥18 years who had completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months before enrollment at 13 healthcare sites in Australia.. Intervention: CV0701 mRNA vaccine (bivalent, encoding ancestral D614G and Omicron BA.4–5 spike proteins) at three dose levels: 3+3 µg, 6+6 µg, or 12+12 µg; or CV0601 mRNA vaccine (monovalent, encoding Omicron BA.4–5 spike protein). Compared with: Licensed Original Wuhan/Omicron BA.4–5 bivalent mRNA COVID-19 vaccine. n = 425. 13 healthcare sites in Australia.

Key findings

425 participants vaccinated; 381 included in Day 29 per-protocol immunogenicity analysis CV0701 mRNA vaccine showed dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4–5 Neutralizing titers declined by Days 91 and 181 but remained above baseline

Safety

No vaccine-related serious adverse events or myocarditis/pericarditis cases reported; most solicited events were mild to moderate

Who this may help

These results support continued development of bivalent and monovalent mRNA COVID-19 vaccines with acceptable tolerability profiles comparable to licensed vaccines. However, the absence of clinical efficacy data and reliance on immunogenicity surrogates means this cannot yet inform changes to vaccination practice; phase 3 efficacy data will be required.

Plain-language summary

Phase 2 randomized active-controlled trial in 425 vaccinated adults showing dose-dependent immunogenicity and acceptable safety profile for investigational mRNA vaccines comparable to licensed comparator, but requiring Phase 3 confirmation before clinical adoption.

Study design

As stated by the source record.

MethodsHealthy adults ≥18 years with completed primary COVID-19 mRNA vaccination ≥3 months prior were randomized 1:1:1:1:1 to receive one of three dose levels of CV0701 bivalent mRNA vaccine (3+3, 6+6, or 12+12 µg), CV0601 monovalent mRNA vaccine, or licensed Original Wuhan/Omicron BA.4–5 bivalent mRNA vaccine. Reactogenicity and safety were assessed post-vaccination; immunogenicity (neutralizing titers and T-cell responses) were measured at Day 8, 29, 91, and 181.

DesignRandomized, multi-center, active-controlled, observer-blind phase 2 trial

PopulationHealthy adults aged ≥18 years who had completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months before enrollment at 13 healthcare sites in Australia.

Sample size425

InterventionCV0701 mRNA vaccine (bivalent, encoding ancestral D614G and Omicron BA.4–5 spike proteins) at three dose levels: 3+3 µg, 6+6 µg, or 12+12 µg; or CV0601 mRNA vaccine (monovalent, encoding Omicron BA.4–5 spike protein)

ComparatorLicensed Original Wuhan/Omicron BA.4–5 bivalent mRNA COVID-19 vaccine

Setting13 healthcare sites in Australia

Reported figures

Quoted from the source exactly as published.

Sample size425

Per-protocol immunogenicity analysis population381

Randomization ratio1:1:1:1:1

CV0701-Low dose3 + 3 µg mRNA encoding for each antigen

CV0701-Med dose6 + 6 µg mRNA encoding for each antigen

CV0701-High dose12 + 12 µg mRNA encoding for each antigen

Clinical bottom line

Caveats

Surrogate endpoints (neutralizing titers, T-cell counts) used; no clinical efficacy or disease outcome data reported
Single-country study (Australia) limits geographic generalizability
Participants were previously vaccinated; findings may not generalize to vaccine-naive populations
No p-values, confidence intervals, or statistical comparisons between treatment groups reported in the provided text

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

strong

Randomized, multi-center, active-controlled, observer-blind phase 2 design with licensed vaccine comparator.

Directness

moderate

Immunogenicity endpoints (neutralizing titers, T-cell responses) are surrogate markers; no clinical outcomes reported.

Consistency

moderate

Both investigational vaccines showed similar immune responses; dose-dependent effect observed for CV0701.

Risk of bias

moderate

Observer-blind design reduces bias; active-controlled reduces placebo effects; no blinding details for participants reported.

Sample adequacy

moderate

425 vaccinated, 381 in Day 29 per-protocol analysis; adequate for phase 2 but not powered for rare safety events.

Source abstract

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults ≥18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Stefano BerrèAntibodies, NeutralizingMartin Robert GaudinskiVaccines, SyntheticEmna BabaAnastasia KuznetsovaImmunogenicity, VaccineAntibodies, ViralRobynne WongTapiwa Ganyani