In a recent study posted to the medRxiv* preprint server, researchers reported the immunogenicity,  efficacy, and safety of the MVA-BN (modified vaccinia Ankara-Bavarian Nordic)-RSV (respiratory syncytial virus) vaccine against RSV-A (RSV subtype A) Memphis 37b strain in a human challenge trial.

Study: Decreased Viral Load, Symptom Reduction, and Prevention of Respiratory Syncytial Virus Infection with MVA-BN-RSV Vaccine. Image Credit: ART-ur/Shutterstock

Background

RSV infections cause a substantial health burden amongst infants and adults, but an authenticated anti-RSV vaccine is lacking. A lot of the RSV vaccines under development encode the RSV F protein. The MVA-BN-RSV vaccine is a recent vector vaccine encoding RSV surface proteins [fusion (F), glycoprotein (G)-(A),(B)], and internal proteins [M2-1 and nucleoprotein (N)], that has induced immunological responses and reported protected amongst animals and in initial clinical evaluation trials.

In regards to the study

In the current study, researchers documented MVA-BN-RSV vaccine immunogenicity, efficacy, and safety against Memphis 37b infection in a human challenge clinical trial conducted in London, United Kingdom (UK), between January and November 2021.

The clinical trial was a double-blinded, phase 2a, placebo-controlled randomized clinical trial comprising healthy participants aged from 18 years to 50 years with expected RSV susceptibility [on the basis of neutralizing antibody (nAb) titers] during screening. Participants were randomly allocated into two groups in a 1:1 ratio to receive either intramuscular MVA-BN-RSV vaccinations or equal volumes of placebo Tris-buffered saline vaccines.

After 4 weeks, individuals were challenged with five log10 PFU (plaque-forming units) of Memphis 37b at a dose of. Blood specimens were obtained for Ab titer and cell-based marker assessments pre-vaccination, seven days post-vaccination for cell-based markers, and two weeks post-vaccination for Ab titers. As well as, blood was drawn six months post-vaccination and on day 5, day 10, and day 28 post-RSV challenge. Viral load was determined by qRT-PCR (quantitative reverse transcription-polymerase chain response) evaluation from nasal wash samples and RSV cultivation experiments.

RSV symptom data were obtained throughout the quarantine period. Participants used memory aid diary cards to acquire data on local and systemic reactions on the day of vaccination as much as one-week post-vaccination and rated symptoms experienced on the initial quarantine day, on the last quarantine day, and thrice every day between the initial and last days. Nasal wash samples were collected two times every day between day 2 and day 11 post-challenge and once on the last day of quarantine.

Plaque assays were performed to evaluate RSV replication. Participant sera were analyzed using ELISA (enzyme-linked immunosorbent assays) to measure anti-RSV immunoglobulin G (IgG) and IgA titers and by PRNT (plaque reduction neutralization tests) to measure nAb titers against RSV-A, B. Further, ELISpot (EL immune-spot) assays were performed for IFN-γ (interferon-gamma)-and IL-4 (interleukin-4) PMBC (peripheral blood mononuclear cell) enumeration as a response to RSV proteins.

MVA-BN-RSV vaccine efficacy was evaluated for the PP (per-protocol) population, comprising vaccinated and RSV-challenged who provided nasal wash samples at the least as much as the tenth quarantine day. The ITTC [intent-to-treat (challenge)] population comprised vaccinated and RSV-challenged individuals evaluated for the supportive-type analyses. Vaccine safety was evaluated amongst all vaccinees (safety population). Logistic regression modeling was performed to explore pre-RSV challenge immunological markers having prognostic value for symptomatic infections by RSV.

Results

Out of 74 study participants, 36 and 38 received MVA-BN-RSV vaccines and placebo vaccines, respectively, and 31 and 32 were RSV-challenged. All (except one) individuals formed the protection evaluation dataset, and five individuals from each group weren’t challenged with Memphis 37b. In consequence, 63 study participants formed the ITTc dataset. Further, viral load assessment specimens till day 10 were unavailable for one individual per group. Thus, 61 individuals comprised the PP dataset.

Viral load from nasal wash samples was significantly lower amongst MVA-BN-RSV vaccinees than placebo vaccinees. Likewise, symptom scores were also lower post-MVA-BN-RSV vaccination. Serological anti-RSV IgA and IgG titers and nAb titers increased by four-fold and two-fold post-MVA-BN-RSV vaccinations, respectively, and robust cellular responses were observed, particularly against the inner RSV proteins. Pain on the injection site was reported for MVA-BN-RSV vaccines; nevertheless, there have been no serious opposed events.

Based on qRT-PCR-based a priori efficacy definitions, MVA-BN-RSV efficacy ranged between 10% for infections confirmed by laboratories only and 59% for those confirmed by laboratory reports and by ≥1 RSV grade ≥2 symptom presence. The viral culture experiments showed 89% MVA-BN-RSV vaccine efficacy in stopping infections, which remained unaltered after including clinical symptoms. Amongst MVA-BN-RSV vaccinees, RSV shedding ended inside 4 days typically, whereas the virus continued shedding for six days or longer amongst placebo vaccinees.

The GMSFUs (geometric mean spot-forming units) for IFN-γ-expressing PBMCs were elevated by two-fold to six-fold inside every week of MVA-BN-RSV vaccination, to a bigger extent than that observed post-placebo vaccination, especially against RSV N and M2-1. Quite the opposite, GMSFUs for IL-4-expressing PBMCs were persistently low throughout the study, indicative of type 1 helper- T (Th1)-based cell-mediated responses. The estimated potential for symptomatic infections by RSV by way of pre-RSV challenge IgA titers most robustly represented RSV infection prognosis, with greater values representing greater protection.

Overall, the study findings showed that MVA-BN-RSV vaccinations reduced viral loads, were effective against laboratory-confirmed symptomatic RSV infections, and conferred humoral and cell-mediated immunity with none serious vaccination-related opposed events.

*Necessary notice

medRxiv publishes preliminary scientific reports that should not peer-reviewed and, subsequently, shouldn’t be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.