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 F protein of the virus. 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.

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein

“…A significant reduction in viral load was observed in the vaccine group compared with the placebo group ( p = 0.017). Additionally, vaccinated subjects showed a significant reduction in clinical symptoms typically associated with RSV infection, demonstrating a vaccine efficacy of 79–89% for preventing symptomatic RSV infection [ 63 , 64 , 65 , 66 ]. Vaccine efficacies of 86.7–100% and 51.9–55.1% (conservative definition) have been reported for RSVpreF [ 55 ] and Ad26.RSV.preF [ 58 ], respectively, for preventing symptomatic infection in healthy adults.…”