Immunogenicity and safety of bivalent recombinant RSV preF vaccine vs AS01E‑adjuvanted RSV preF vaccine in lung and allogeneic HSCT recipients: Phase 2

The primary objective is to evaluate the RSVpreF-binding antibody response to each of the two vaccine strategies one month after completion of the dosing schedule, with separate analyses for lung transplant recipients and allogeneic hematopoietic stem cell transplant recipients; this measurement serves as a direct indicator of vaccine‑induced immunogenicity and informs potential protection against respiratory syncytial virus in these high‑risk populations. Secondary objectives include: • assessment and comparison of the neutralizing antibody response to RSV‑A and RSV‑B one month post‑vaccination; • characterization and longitudinal monitoring of the systemic humoral immune response up to twelve months; • evaluation of the mucosal humoral immune response in oral fluid at one month; • determination and comparison of reactogenicity and overall safety; • analysis of the determinants of humoral response influencing immunogenicity; • description of medically attended RSV infection episodes among vaccinated participants; • characterization of RSV isolates from such episodes; • assessment of systemic and mucosal immunity at the time of infection; and • comparison of immune responses between participants with infection and matched vaccinated controls without infection.

The trial enrolled adult patients, both male and female, who were either recipients of a lung transplant performed at least three months before the first vaccine dose or recipients of an allogeneic haematopoietic stem cell transplant conducted between three months and five years prior to vaccination. All participants were required to be at least 18 years of age at inclusion, to be under active follow‑up at a study centre, and to provide written informed consent. The sponsor did not provide information regarding the total number of participants enrolled. No additional lifestyle or health status details were specified beyond the transplant history and general inclusion requirements.

The phase II study is a randomized, double‑blind, controlled trial evaluating two intramuscular respiratory syncytial virus vaccine strategies in adult recipients of lung transplantation or allogeneic haematopoietic stem cell transplant. Participants are screened (Visit 0) to confirm eligibility, including transplant timing (≥3 months for lung, 3 months to 5 years for stem cell), active follow‑up, age ≥18 years, and consent. Eligible subjects are randomly assigned in a 1:1 ratio to receive either the bivalent RSV vaccine (Abrysvo) or the adjuvanted RSV vaccine (Arexvy) in a two‑dose series administered at baseline (Visit 1) and a second dose 30 days later (Visit 1b for the Arexvy arm). The primary immunogenicity assessment occurs one month after the second dose (Visit 2), with additional blood and oral fluid sampling at baseline, pre‑dose‑2, Visit 2, and at 12 months post‑first dose (Visit 3). Safety monitoring includes solicited adverse events for 7 days and unsolicited events for 30 days after each vaccination, with ongoing surveillance for serious adverse events and RSV infection throughout the study period. Participant involvement spans approximately 12 months from the first vaccination to the end‑of‑study visit. Early termination may occur if a participant withdraws consent, experiences a vaccine‑related serious adverse event, or is lost to follow‑up, in which case data collected up to the point of discontinuation are retained for analysis.

The investigational product identified as Abrysvo is supplied as a powder for reconstitution with solvent to produce a solution for injection. Each administered dose consists of 0.5 ml of the reconstituted vaccine, delivered by the intramuscular route. The formulation contains a bivalent recombinant antigen composed of stabilized prefusion F proteins from respiratory syncytial virus subgroups A (847A) and B (847B). Dosing is scheduled as a single injection, with the administration date recorded in the participant’s case report form and the injection site observed for a minimum of 30 minutes post‑administration to assess immediate reactogenicity.

The second investigational product, Arexvy, is provided as a powder for suspension intended for intramuscular injection. The administered volume is 0.5 ml of the suspension, containing a recombinant prefusion F glycoprotein of respiratory syncytial virus adjuvanted with AS01E. The vaccine is given as a single dose, and similar post‑injection observation procedures are applied. Compliance with the dosing schedule is verified by confirming the preparation and administration timestamps in the electronic data capture system.

Adherence to the vaccination protocol is monitored through scheduled clinic visits at baseline, the day of vaccination, and follow‑up visits at 1 month and additional time points as defined in the protocol. Participants maintain a vaccination diary documenting any local or systemic symptoms, and study staff perform source‑document verification of diary entries and injection records to ensure accurate compliance reporting.

The primary efficacy assessment is the proportion of participants in each vaccine group who achieve a seroresponse one month after completing the vaccination series (visit 2). A seroresponse is defined as either seroconversion or at least a four‑fold increase in RSVpreF‑binding serum IgG concentration from baseline, as quantified by a validated enzyme immunoassay (EIA).

Secondary efficacy evaluations include: 

• Measurement of RSV‑A and RSV‑B serum 50 % neutralizing geometric mean titres (GMT) and the corresponding geometric mean fold rises (GMFR) using a standardized RSV neutralization assay at baseline and visit 2.
• Determination of geometric mean concentrations (GMC) of RSVpreF‑binding serum IgG, the proportion achieving a ≥2‑fold rise, and log‑dilution values for 50 % signal inhibition in D25‑ and palivizumab‑competitive EIAs at baseline, pre‑dose‑2 (arm B), visit 2, and one‑year post‑first dose (visit 3).
• Assessment of RSVpreF‑binding oral fluid IgA GMT and GMFR by EIA at baseline and visit 2.
• Exploratory analyses of humoral immunogenicity determinants (age, transplantation timing, immunosuppression, graft‑versus‑host disease) collected at baseline, interim visits, and visit 3.
• Descriptive evaluation of medically attended RSV infection episodes, including viral load sequencing and immunogenicity parameters at the time of infection.

Efficacy parameters are obtained using validated laboratory assays (enzyme immunoassay, neutralization assay) performed on serum and oral fluid samples collected at predefined study visits: baseline (visit 1), pre‑dose‑2 for arm B (visit 1b), one month after the final vaccine dose (visit 2), and one year after the first dose (visit 3). Additional sampling occurs at the onset of a confirmed RSV infection. Data are analyzed by calculating proportions, geometric means, and fold‑rise ratios, with comparisons made between vaccine groups within each transplant subcohort.