Immunogenicity and Safety of the Bivalent Respiratory Syncytial Virus Prefusion F Subunit Vaccine in Immunocompromised or Renally Impaired Adults

Abstract

Background/Objectives: Individuals with immunocompromising conditions are at high risk of developing severe respiratory syncytial virus (RSV) illness. This phase 3, single-arm study assessed the safety and immunogenicity of the bivalent RSV prefusion F protein-based (RSVpreF) 120-µg vaccine in immunocompromised and renally impaired adults. Methods: Participants were stratified by age group (18-<60-year-olds; ≥60-year-olds) and received two RSVpreF doses 1 month apart (i.e., Dose 1 and Dose 2, respectively). Reactogenicity events were collected for 7 days after each dose; adverse events through 1 month after the last dose; and serious adverse events, adverse events of special interest, and newly diagnosed chronic medical conditions throughout the study. Results: One month after Dose 1, RSVpreF elicited robust immune responses overall and across age and immunocompromised subgroups. Overall, geometric mean fold rises from before to 1 month after Dose 1 were high for RSV A and RSV B (8.3 and 9.0, respectively); no additional increases 1 month after Dose 2 (7.5 and 7.8) were observed. The most frequent local reaction was pain at the injection site, which was more common after Dose 2 than after Dose 1. The most frequent systemic event after any dose was fatigue. Most local reactions and systemic events were mild or moderate in severity. Adverse event and serious adverse event rates were 13.5% and 7.3% among 18-<60-year-olds and 22.4% and 14.0% among ≥60-year-olds, respectively. Conclusions: A single dose of the RSVpreF vaccine conferred robust immune responses in immunocompromised and renally impaired adults with no safety concerns. (ClinicalTrials.gov Identifier: NCT05842967).

Keywords: RSV; RSVpreF; adults; immunocompromised; immunogenicity; renally impaired; safety.

Figure 1

Neutralizing GMTs and GMFRs together with 95% CIs overall and by age group for RSV A and RSV B (evaluable immunogenicity population). The LLOQ values were 242 and 99 for RSV A and RSV B neutralizing titers, respectively. Any assay results that were less than the LLOQ were set to 0.5 × LLOQ for all GMT and GMFR calculations, except for prevaccination assay results less than the LLOQ where the postvaccination result was greater than or equal to the LLOQ, in which case the prevaccination value was then set to the LLOQ when calculating GMFRs. ^a GMFR from before to 1 month after Dose 2. ^b GMFR from before to 1 month after Dose 1. GMFR = geometric mean fold rise; GMT = geometric mean titer; LLOQ = lower limit of quantitation; RSV = respiratory syncytial virus.

Figure 2

Neutralizing GMTs and GMFRs with 95% CIs by immunocompromising condition for RSV A and RSV B (evaluable immunogenicity population). The LLOQ values were 242 and 99 for RSV A and RSV B neutralizing titers, respectively. Any assay results that were less than the LLOQ were set to 0.5 × LLOQ for all GMT and GMFR calculations, except for prevaccination assay results less than the LLOQ where the postvaccination result was greater than or equal to the LLOQ, in which case the prevaccination value was then set to the LLOQ when calculating GMFRs. ^a GMFR from before to 1 month after Dose 2. ^b GMFR from before to 1 month after Dose 1. GMFR = geometric mean fold rise; GMT = geometric mean titer; ESRD = end-stage renal disease; LLOQ = lower limit of quantitation; NSCLC = non-small cell lung cancer; RSV = respiratory syncytial virus; SOT = solid organ transplantation.

Figure 3

RSV A and RSV B neutralizing titer seroresponse rates 1 month after each RSVpreF vaccination overall and by age group. Data are for the evaluable immunogenicity population. Error bars are the 95% CI. The LLOQ values were 242 and 99 for RSV A and RSV B neutralizing titers, respectively. Seroresponse was defined as achieving a ≥4-fold rise from baseline (before vaccination) if the baseline measurement was above the LLOQ. If the baseline measurement was below the LLOQ, a postvaccination assay result ≥ 4 × LLOQ is considered a seroresponse. LLOQ = lower limit of quantitation; RSV = respiratory syncytial virus; RSVpreF = RSV prefusion F protein−based vaccine.

Figure 4

Local reactions occurring within 7 days of RSVpreF vaccination by age group. Data are for the electronic diary safety population, and error bars are the 95% CIs. N values for the 18 to <60 years old group are 96, 94, and 96 for D1, D2, and any dose, respectively. Corresponding values for the ≥60 years old group are 107, 105, and 107. The numbers above the bars are the percentage of participants with the specific local reaction overall. No severe local reactions were observed. The severity rating scale is shown in Table S2. D1 = Dose 1; D2 = Dose 2; RSVpreF = RSV prefusion F protein−based vaccine.

Figure 5

Systemic events occurring within 7 days of RSVpreF vaccination by age group. Data are for the electronic diary safety population, and error bars are the 95% CIs. N values for the 18 to <60 years old group are 96, 94, and 96 for D1, D2, and any dose, respectively. Corresponding values for the ≥60 years old group are 107, 105, and 107. The numbers above the bars are the percentage of participants with the specific local reaction overall. The severity rating scale is shown in Table S2. D1 = Dose 1; D2 = Dose 2; RSVpreF = RSV prefusion F protein−based vaccine.

Figure 6

Percentages of participants reporting AEs by age group after receiving the RSVpreF vaccination. Data are for the safety population and are for all AEs excluding prespecified events (i.e., any prespecified events that are electronic diary-specified local reactions and systemic events reported in the AE case report form during the electronic diary collection period, apart from SAEs). AEs were reported through 1 month after the second RSVpreF vaccination; SAEs, NDCMCs, AEs leading to withdrawal, and AESIs are those reported throughout the study. AE = adverse event; AESI = adverse event of special interest; NDCMC = newly diagnosed chronic medical condition; RSVpreF = RSV prefusion F protein−based vaccine; SAE = serious adverse event.