Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

The ConquerRSV phase 2–3 trial evaluated the mRNA-1345 vaccine (Moderna) encoding the stabilized RSV prefusion F glycoprotein in 35,541 adults ≥60 years old across 22 countries. Participants received a single 50 μg dose of mRNA-1345 or placebo. Primary efficacy endpoints showed:

• RSV-associated lower respiratory tract disease (≥2 symptoms):

  • Vaccine efficacy: 83.7% (95.88% CI: 66.0–92.2)

• RSV-associated lower respiratory tract disease (≥3 symptoms):

  • Vaccine efficacy: 82.4% (96.36% CI: 34.8–95.3)

• RSV-associated acute respiratory disease (≥1 symptom):

  • Vaccine efficacy: 68.4% (95% CI: 50.9–79.7) Efficacy remained high across RSV subtypes (A: 91.7%, B: 68.5) and in subgroups stratified by age (70–79 yr: 95.4%), frailty, and comorbid conditions. Safety:

• Local reactions: 58.7% (mRNA-1345) vs 16.2% (placebo); mostly injection-site pain

• Systemic reactions: 47.7% vs 32.9%; mostly fatigue, headache, myalgia

• Serious adverse events: 2.8% in both groups; no safety signals identified

• No reports of myocarditis, Guillain–Barré, or vaccine-related deaths The authors conclude mRNA-1345 is a safe, highly efficacious single-dose RSV vaccine in older adults, with protection sustained through a median 112-day follow-up. Further data on duration and boosting are pending.

The ConquerRSV phase 2–3 trial evaluated the mRNA-1345 vaccine (Moderna) encoding the stabilized RSV prefusion F glycoprotein in 35,541 adults ≥60 years old across 22 countries. Participants received a single 50 μg dose of mRNA-1345 or placebo. Primary efficacy endpoints showed:

• RSV-associated lower respiratory tract disease (≥2 symptoms):

  • Vaccine efficacy: 83.7% (95.88% CI: 66.0–92.2)

• RSV-associated lower respiratory tract disease (≥3 symptoms):

  • Vaccine efficacy: 82.4% (96.36% CI: 34.8–95.3)

• RSV-associated acute respiratory disease (≥1 symptom):

  • Vaccine efficacy: 68.4% (95% CI: 50.9–79.7) Efficacy remained high across RSV subtypes (A: 91.7%, B: 68.5) and in subgroups stratified by age (70–79 yr: 95.4%), frailty, and comorbid conditions. Safety:

• Local reactions: 58.7% (mRNA-1345) vs 16.2% (placebo); mostly injection-site pain

• Systemic reactions: 47.7% vs 32.9%; mostly fatigue, headache, myalgia

• Serious adverse events: 2.8% in both groups; no safety signals identified

• No reports of myocarditis, Guillain–Barré, or vaccine-related deaths The authors conclude mRNA-1345 is a safe, highly efficacious single-dose RSV vaccine in older adults, with protection sustained through a median 112-day follow-up. Further data on duration and boosting are pending.