Decreased Viral Load, Symptom Reduction, and Prevention of Respiratory Syncytial Virus Infection with MVA-BN-RSV Vaccine

ABSTRACT Background Respiratory syncytial virus (RSV) causes significant disease burden in infants and older adults. Most vaccines in development focus on the virus’s F protein. MVA-BN-RSV is a novel vectored vaccine encoding internal and external proteins from both RSV subtypes. Methods In a phase 2a trial, participants aged 18 to 50 years selected for low RSV titers were randomized to receive MVA-BN-RSV or placebo, then challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes and virus cultivation, and RSV symptoms were collected throughout quarantine. Antibody titers and cellular markers were assessed before and after vaccination and challenge. Results Of 74 participants randomized, 36 received MVA-BN-RSV and 37 received placebo; 31 and 32, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (p=0.017) for MVA-BN-RSV (median=0.00) compared to placebo (median=49.05). Total symptom scores also were lower with MVA-BN-RSV. Vaccine efficacy in preventing infection confirmed by viral culture was 88.5% (CI: 14.8%; 98.5%). Immunoglobulin A and G in serum increased about 4-fold after MVA-BN-RSV vaccination, which was greater than the placebo response to challenge, and neutralizing antibody titer increased about 2-fold. Cellular responses were robust, particularly to the internal RSV proteins. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination. Conclusion MVA-BN-RSV vaccination resulted in lower viral load and was effective against laboratory-confirmed symptomatic infection. Humoral and cellular responses support broad immunogenicity of the vaccine. No safety issues were identified with vaccination. Clinical Trial Registry Number NCT04752644