Background
Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective.
Methods
This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN®-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule.
Results
A single dose increased the levels of neutralizing (PRNT to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (IFN-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T cell responses (up to 2.8-fold from pre-boost levels). No drug-related serious adverse events were reported.
Conclusions
MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings.
Clinical Trials Registration
NCT02873286
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.
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