Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered With Seasonal Inactivated Influenza Vaccine in Older Adults

Abstract

Background: Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines.

Methods: The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy adults aged ≥65 years in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein-based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% confidence interval >.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data.

Results: Of 1403 participants randomized, 1399 received vaccinations (median age, 70; range, 65‒91 years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin.

Conclusions: The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older-adult population.

Clinical trials registration: https://clinicaltrials.gov/study/NCT05301322.

Keywords: RSVpreF; coadministration; influenza; respiratory syncytial virus; seasonal inactivated influenza vaccine.

Figure 1.

Study design. Abbreviations: RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine; SIIV, seasonal inactivated influenza vaccine.

Figure 2.

Participant disposition. “Enrolled” refers to participants who were recruited by study site staff and gave written informed consent, regardless of whether they were randomized. Abbreviations: AE, adverse event; RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine; SIIV, seasonal inactivated influenza vaccine.

Figure 3.

Geometric mean ratios (95% CIs) for influenza strain HAI titers and RSV neutralizing titers at 1 month after vaccination. Data are for the evaluable SIIV immunogenicity population and evaluable RSV immunogenicity population. Two-sided 95% CIs were based on the Student’s t distribution. The dotted line represents the prespecified noninferiority margin. The number of participants with valid and determinate assay results for the specified assay in the respective evaluable immunogenicity population was 674–681. Abbreviations: CI, confidence interval; GMR, geometric mean ratio; HAI, hemagglutination inhibition; NT, 50% neutralizing titer; RSV, respiratory syncytial virus; RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine; SIIV, seasonal inactivated influenza vaccine.

Figure 4.

Local reactions (A) and systemic events (B) reported within 7 days of vaccination. Data are for the safety population. Severity grading of the specific local reactions and systemic events is provided in Supplementary Table 1. Error bars represent 95% CIs computed using the Clopper-Pearson method and numbers above the bars indicate the percentage of participants in each group reporting the specified event (rounded to whole numbers). Local reactions were reported by participants at the RSVpreF or placebo injection site only. RSVpreF + SIIV (n = 701); placebo (n = 681); placebo + SIIV (n = 693); RSVpreF alone (n = 686). Abbreviations: CI, confidence interval; RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine; SIIV, seasonal inactivated influenza vaccine.

Figure 5.

Adverse event summary within 1 month of each vaccination. Data are for the safety population. The numbers above the bars show the percentage of participants who experienced 1 or more of the specified type of event within 1 month after the respective vaccination. Error bars represent exact 2-sided 95% CIs calculated using the Clopper-Pearson method. An immediate AE was defined as any AE that occurred within the first 30 minutes after administration of study vaccine (RSVpreF or placebo). Related AEs were determined by the investigator. Abbreviations: AE, adverse event; CI, confidence interval; RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine; SIIV, seasonal inactivated influenza vaccine.