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Clinical Trial
. 2024 Oct 15;79(4):1074-1084.
doi: 10.1093/cid/ciae364.

Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age

Collaborators, Affiliations
Clinical Trial

Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age

Murdo Ferguson et al. Clin Infect Dis. .

Abstract

Background: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions.

Methods: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed.

Results: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups.

Conclusions: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds.

Clinical trial registration: ClinicalTrials.gov: NCT05590403.

Keywords: chronic conditions; humoral immunity; respiratory syncytial virus; safety; vaccination.

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Conflict of interest statement

Potential conflicts of interest . H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., C. V., and V. H. are/were GSK employees at the time when the study was designed and/or conducted. H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., and V. H. hold shares in GSK as part of their employee remuneration. M.-P. D. is a co-applicant on a pending patent filed by GSK. M. F. received study-related payments for training and study conduct from GSK. T. F. S. received honoraria for lectures from AstraZeneca, Bavarian Nordic, Biogen, CSL-Seqirus, GSK, Janssen-Cilag, Merck-Serono, Moderna, Novavax, MSD, Pfizer, Roche, Sanofi-Aventis, and Takeda; he participated on advisory boards for Bavarian Nordic, CSL-Seqirus, BioNTech, GSK, Moderna, Novavax, and Takeda. S. A. N. declares study-related payments to his institution from GSK and support from GSK to attend investigators meetings. J. R.-G. declares study-related payments from GSK and honoraria and support for attending meetings and/or travel from GSK, Pfizer, and Sanofi-MSD; he also participated on data and safety monitoring boards or advisory boards from GSK and Pfizer. C. Z. received grants from GSK for the conduct of this study and support from GSK for attending meetings. J. G. declares study-related payments from GSK; grants from Novartis, Pharmalog, New Amsterdam Pharma, Syneos, Winecker Pharma, and Lilly; and consulting fees, honoraria, payment for expert testimony, and support for attending meetings and/or travel from GSK. C. V.-P. is a former employee of QPS Netherlands B.V. The other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Plain language summary.
Figure 2.
Figure 2.
Study design. Abbreviations: 50–59-AIR-placebo, group of 50–59-year-old participants at increased risk for respiratory syncytial virus (RSV) disease who received placebo; 50–59-AIR-RSV, group of 50–59-year-old participants at increased risk for RSV disease who received RSV prefusion F protein–based vaccine (RSVPreF3 OA); 50–59-non-AIR-placebo, group of 50–59-year-old participants without increased risk for RSV disease who received placebo; 50–59-non-AIR-RSV, group of 50–59-year-old participants without increased risk for RSV disease who received RSVPreF3 OA; ≥60-RSV, group of ≥60-year-old participants who received RSVPreF3 OA.
Figure 3.
Figure 3.
Flow of participants. For eliminations from the per-protocol sets for immunogenicity, multiple reasons could apply for 1 participant; all reasons are listed in the figure. Abbreviations: (S)AE, (serious) adverse event; 50–59-AIR-placebo, group of 50–59-year-old participants at increased risk for respiratory syncytial virus (RSV) disease who received placebo; 50–59-AIR-RSV, group of 50–59-year-old participants at increased risk for RSV disease who received RSV prefusion F protein–based vaccine (RSVPreF3 OA); 50–59-non-AIR-placebo, group of 50–59-year-old participants without increased risk for RSV disease who received placebo; 50–59-non-AIR-RSV, group of 50–59-year-old participants without increased risk for RSV disease who received RSVPreF3 OA; ≥60-RSV, group of ≥60-year-old participants who received RSVPreF3 OA. aParticipants in the cell-mediated immunity subset were recruited from a selected number of countries and centers (Supplementary Methods). In total, 339 participants were included in the exposed set of the cell-mediated immunity subset.
Figure 4.
Figure 4.
RSV-A (A) and RSV-B (B) geometric mean neutralization titers and mean geometric increases (per-protocol set for humoral immunogenicity). Confidence intervals (CIs) are depicted as error bars. Abbreviations: ED60, estimated dilution 60; MGI, mean geometric increase (ie, geometric mean of the within-participant ratios of the post-vaccination over the pre-vaccination neutralization titers); Placebo, received placebo; POST, 1 month after vaccination; PRE, before vaccination; RSV, respiratory syncytial virus; 50–59-AIR, group of 50–59-year-old participants at increased risk for RSV disease; 50–59-non-AIR, group of 50–59-year-old participants without increased risk for RSV disease; ≥60, group of ≥60-year-old participants.
Figure 5.
Figure 5.
Frequency of RSVPreF3-specific-CD4+ T cells expressing ≥2 markers including ≥1 cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL-13, and IL-17 (per-protocol set for cell-mediated immunity). Abbreviations: CD40L, CD40 ligand; IFN-γ, interferon-γ; IL, interleukin; max, maximum; min, minimum; Placebo, received placebo; POST, 1 month after vaccination; PRE, before vaccination; Q1, first quartile; Q3, third quartile; RSV, received respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA); RSVPreF3, respiratory syncytial virus prefusion F protein; TNF-α, tumor necrosis factor-α; 50–59-non-AIR, group of 50–59-year-old participants without increased risk for RSV disease; 50–59-AIR, group of 50–59-year-old participants at increased risk for RSV disease; ≥60, group of ≥60-year-old participants.
Figure 6.
Figure 6.
Solicited adverse events within 4 days after RSVPreF3 OA or placebo administration (exposed population). Confidence intervals are depicted as error bars. Fever was defined as a temperature ≥38.0°C. Grade 3 adverse events were defined as administration-site erythema or swelling with a diameter >100 mm, fever with a temperature >39.0°C, and administration-site pain, headache, fatigue, myalgia, and arthralgia that prevented normal activity. Abbreviations: Placebo, received placebo; RSV, received respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA); 50–59-non-AIR, group of 50–59-year-old participants without increased risk for RSV disease; 50–59-AIR, group of 50–59-year-old participants at increased risk for RSV disease; ≥60, group of ≥60-year-old participants.

Comment in

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