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Background Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV proteins. Methods In a phase 2a randomized double-blind, placebo-controlled trial, healthy participants aged 18 to 50 years received MVA-BN-RSV or placebo, then were challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes. RSV symptoms were collected. Antibody titers and cellular markers were assessed before and after vaccination and challenge. Results After receiving MVA-BN-RSV or placebo, 31 and 32 participants, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (p = 0.017) for MVA-BN-RSV (median = 0.00) than placebo (median = 49.05). Total symptom scores also were lower (median = 2.50 and 27.00, respectively; p = 0.004). Vaccine efficacy against symptomatic, laboratory-confirmed or culture-confirmed infection was 79.3% to 88.5% (p = 0.022 and 0.013). Serum immunoglobulin A and G titers increased ∼4-fold after MVA-BN-RSV vaccination. Interferon-γ-producing cells increased 4- to 6-fold after MVA-BN-RSV in response to stimulation with the encoded RSV internal antigens. 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 symptom scores, fewer confirmed infections, and induced humoral and cellular responses.

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.