LB747. Immune Responses of the Recombinant MVA-BN-RSV Vaccine against Respiratory Syncytial Virus Infection in an RSV Human Challenge Trial (HCT) in Healthy Adult Participants


 
 
 Respiratory Syncytial Virus (RSV) causes considerable morbidity and mortality in infants and older adults. Even though throughout life multiple infections occur, there is no natural protection. The MVA-BN vector-based RSV vaccine was designed to induce humoral and cellular RSV-specific immune responses against 5 RSV proteins (F, G [A and B subtype], M2-1 and N). We present immune response data after vaccination and challenge with an RSV-A strain in a human challenge trial conducted in healthy, young adults.
 
 
 
 In a double-blinded, placebo controlled, HCT (EudraCT-no. 2020-004814-36) subjects (N=61) were randomly vaccinated with MVA-BN-RSV or placebo (30 MVA-BN-RSV and 31 placebo), intranasally challenged with RSV-A (Memphis-37b strain) after 28 days and quarantined for 12 days. Exploratory endpoints included RSV specific humoral and cellular immune responses after vaccination and after challenge throughout follow up until Day 155 assessed by treatment group and infected vs non infected in subjects receiving either MVA-BN-RSV or placebo.
 
 
 
 For all serum-based RSV specific antibody assays including ELISA IgG, IgA and neutralizing antibody assays PRNT A and B, antibody titers increased after vaccination in the MVA-BN-RSV group and stayed above baseline level over the entire study without being influenced by the challenge with Memphis-37b. In the placebo group, the antibody titers increased after challenge and were not affected by vaccination.
 The geometric mean spot forming units (GMSFUs) based on IFN-γ producing PBMCs for the stimulating agents pool F, G(A), G(B), N, M2-1 and RSV increased after vaccination in the MVA-BN-RSV group, peaking at Day 7 post vaccination for most peptide pools without any effect after challenge. In the placebo group, there was no increase after vaccination, but an increase with a peak on Day 10 post challenge was observed for all pools.
 
 
 
 The results confirmed the broad humoral and cellular immune response elicited by the vaccination with MVA-BN-RSV which was not further boosted by the challenge virus.
 
 
 
 Darja Schmidt, PhD, Bavarian Nordic: Employed|Bavarian Nordic: Warrants Günter Silbernagl, MSc, Bavarian Nordic: Employed|Bavarian Nordic GmbH: employee Employee and received warrants Elke Jordan, PhD, Bavarian Nordic: Employed Victoria A. JENKINS, PhD MBA, Bavarian Nordic: Employed Stephanie Schultz, Dipl Biol, Bavarian Nordic: Employed Heinz Weidenthaler, Dr med, Bavarian Nordic: Employed.
