Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Oct 15;79(4):1088-1098.
doi: 10.1093/cid/ciae365.

Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial

Rebecca Clark  1 , Sam Davies  2 , Jorge Labrador  3 , Paul Loubet  4 , Silvina Natalini Martínez  5 , Helena Moza Moríñigo  6 , Jean-François Nicolas  7 , Mercè Pérez Vera  8 , Mika Rämet  9 , Maria Henar Rebollo-Rodrigo  10 , Iván Sanz-Muñoz  11   12 , Nancy Dezutter  13 , Sophie Germain  13 , Marie-Pierre David  13 , Amulya Jayadev  14 , Hiwot Amare Hailemariam  13 , Shady Kotb  13 , Nadia Meyer  13
Affiliations
Clinical Trial

Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial

Rebecca Clark et al. Clin Infect Dis. .

Abstract

Background: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds.

Methods: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed.

Results: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups.

Conclusions: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine.

Clinical trials registration: NCT05568797.

Keywords: RSVPreF3 OA; adjuvanted seasonal influenza vaccine; concurrent administration; immunogenicity; safety.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. R. C. runs RSV studies at her trial site with Moderna and GSK and received NIHR funding to attend the World Vaccine Congress (October 2022) as part of the UK delegation; she is the Deputy Specialty Lead and the Clinical Lead for vaccine research at the North West Coast Clinical Research Network. P. L. received consulting fees from GSK and Pfizer, declares payments or honoraria from Janssen, GSK, Moderna, AstraZeneca, Pfizer, and Sanofi, and financial support for attending meetings and/or travel from AstraZeneca, Pfizer, and Sanofi. J.-F. N., M. R., and I. S.-M. report grants and funding from GSK to their institutions for conducting this clinical trial. N. D., S. G., M.-P. D., A. J., H. A. H., S. K., and N. M. are or were employed by GSK at the time the study was designed, initiated, and/or conducted. N. D., M.-P. D., H. A. H., S. K., and N. M. have stock options or shares from GSK. N. D. also reports stocks from Haleon and patents on vaccination against RSV (numbers 2218080.6 and 2303002.6). M.-P. D. is a co-applicant on a pending patent filed by GSK. S. N. M. declares being a Principal Investigator on the current trial. S. D., J. L., H. M. M., M. P. V., and M. H. R. -R. have no conflicts of interest to declare. The authors declare no other financial or non-financial relationships. 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

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Study design. Abbreviations: AE, adverse event; FLU-aQIV, adjuvanted inactivated seasonal quadrivalent influenza vaccine; pIMD, potential immune-mediated disease; RSVPreF3 OA, respiratory syncytial virus prefusion F protein-based vaccine; SAE, serious adverse event. aApplies to Control group only.
Figure 2.
Figure 2.
Flow of participants. For eliminations from the PPS, multiple reasons could apply for 1 participant; all reasons are listed in the figure. Co-Ad, group of participants who received RSVPreF3 OA and FLU-aQIV concomitantly on day 1. Control, group of participants who received FLU-aQIV on day 1 and RSVPreF3 OA on day 31; N, number of participants in the indicated analysis set and group. Abbreviations: AE, adverse event; FLU-aQIV, adjuvanted inactivated seasonal quadrivalent influenza vaccine; PPS, per-protocol sets for immunogenicity; RSVPreF3 OA, respiratory syncytial virus (RSV) prefusion F protein-based vaccine.
Figure 3.
Figure 3.
Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration, evaluated by adjusted GMT ratios for influenza HI and RSV neutralizing titers A, as well as influenza MN titers for A/Darwin (H3N2) B, (per-protocol sets for flu and RSV analyses). CIs are depicted as error bars. Success criterion for non-inferiority: upper limits of 2-sided 95% CIs for adjusted geometric mean titer (GMT) ratios (Control/Co-Ad) for each FLU-aQIV strain and for RSV-A and RSV-B were ≤1.50 at 1 m post-vaccination. Abbreviations: CI, confidence interval; FLU-aQIV, adjuvanted inactivated seasonal quadrivalent influenza vaccine; HI, hemagglutination inhibition; MN, microneutralization; RSVPreF3 OA, respiratory syncytial virus (RSV) prefusion F protein-based vaccine. aAs the non-inferiority analysis was performed sequentially, and the success criterion was not met for A/Darwin (H3N2), non-inferiority for RSV-B neutralization titers was no longer a confirmatory endpoint and was evaluated descriptively.
Figure 4.
Figure 4.
Geometric mean titers and mean geometric increases for influenza strains (A, per-protocol set for flu analysis) and for RSV-A and RSV-B neutralization titers (B, per-protocol set for RSV analysis). Co-Ad, group of participants who received RSVPreF3 OA and FLU-aQIV concomitantly on day 1; Control, group of participants who received FLU-aQIV on day 1 and RSVPreF3 OA on day 31; pre, before FLU-aQIV vaccination (day 1) for flu analysis or before RSVPreF3 OA vaccination (day 1 for Co-Ad group, day 31 for Control group) for RSV analysis; post, 1 m after FLU-aQIV vaccination (day 31) for flu analysis or 1 m after RSVPreF3 OA vaccination (day 31 for Co-Ad group, day 61 for Control group) for RSV analysis. Abbreviations: 1/DIL, 1/dilution; CI, confidence interval; ED60, estimated dilution 60; FLU-aQIV, adjuvanted inactivated seasonal quadrivalent influenza vaccine; MGI, mean geometric increase of the post- versus the pre-vaccination titers; RSVPreF3 OA, respiratory syncytial virus (RSV) prefusion F protein-based vaccine.
Figure 5.
Figure 5.
Solicited administration-site A, and systemic B, adverse events with onset within 7 d after FLU-aQIV and RSVPreF3 OA co-administration or sequential administration (exposed set). 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, administration-site pain, arthralgia, fatigue, headache, and myalgia that prevented normal activity. Co-Ad, group of participants who received RSVPreF3 OA and FLU-aQIV concomitantly on day 1 (visit 1); Control, group of participants who received FLU-aQIV on day 1 (visit 1) and RSVPreF3 OA on day 31 (visit 2). Abbreviations: FLU-aQIV, adjuvanted inactivated seasonal quadrivalent influenza vaccine; MGI, mean geometric increase; RSVPreF3 OA, respiratory syncytial virus (RSV) prefusion F protein-based vaccine.
See this image and copyright information in PMC

Comment in

References

    1. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus: a comprehensive review. Clin Rev Allergy Immunol 2013; 45:331–79. - PMC - PubMed
    1. Nam HH, Ison MG. Respiratory syncytial virus infection in adults. BMJ 2019; 366:l5021. - PubMed
    1. Shi T, Vennard S, Jasiewicz F, Brogden R, Nair H, RESCEU Investigators . Disease burden estimates of respiratory syncytial virus related acute respiratory infections in adults with comorbidity: a systematic review and meta-analysis. J Infect Dis 2022; 226:S17–21. - PubMed
    1. Branche AR, Saiman L, Walsh EE, et al. . Incidence of respiratory syncytial virus infection among hospitalized adults, 2017–2020. Clin Infect Dis 2022; 74:1004–11. - PubMed
    1. Prasad N, Walker TA, Waite B, et al. . Respiratory syncytial virus-associated hospitalizations among adults with chronic medical conditions. Clin Infect Dis 2021; 73:e158–63. - PubMed

Publication types

MeSH terms

Associated data