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A Randomized Phase 1 Clinical Trial of a Respiratory Syncytial Virus and Human Metapneumovirus Combination Protein-Based Virus-like Particle Vaccine in Adults 60-75 Years of Age.

Open forum infectious diseases2025-04-09PubMed
Total: 78.5Innovation: 8Impact: 8Rigor: 8Citation: 7

Summary

In a randomized Phase 1 study of adults aged 60–75 years, a combination RSV/hMPV protein-based VLP vaccine (IVX-A12) was well tolerated and boosted neutralizing antibodies against both viruses up to 3–5-fold by day 28, with responses persisting to day 365. No vaccine-related serious adverse events were observed.

Key Findings

  • Randomized Phase 1 trial in adults 60–75 years evaluated IVX-A12 at multiple dose levels ± MF59 vs placebo.
  • Well tolerated with only mild-to-moderate transient reactions; no vaccine-related serious adverse events.
  • Neutralizing antibody titers increased up to 4× (RSV A), 3× (RSV B), 5× (hMPV A), and 4× (hMPV B) by day 28, with responses maintained around/above baseline through day 365.

Clinical Implications

Although early-phase, the data support advancing combination RSV/hMPV vaccination strategies for older adults pending efficacy trials, potentially simplifying immunization schedules.

Why It Matters

Demonstrates safety and dual-pathogen immunogenicity of a combination respiratory virus vaccine in older adults, supporting development of broader LRTD prevention strategies.

Limitations

  • Phase 1 study not powered for clinical efficacy against LRTD
  • Immunogenicity endpoints limited to neutralizing antibodies without cellular immunity detail in abstract

Future Directions

Proceed to Phase 2/3 efficacy trials in older adults, assess durability, correlates of protection, and potential coadministration with other vaccines.

Study Information

Study Type
RCT
Research Domain
Prevention
Evidence Level
II - Randomized Phase 1 trial demonstrating safety and immunogenicity
Study Design
OTHER