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
Multicenter Study
. 2024 Feb 14;229(2):355-366.
doi: 10.1093/infdis/jiad321.

Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study

Isabel Leroux-Roels  1 , Marc Van Ranst  2 , Corinne Vandermeulen  3 , Carline Vanden Abeele  4 , Nathalie De Schrevel  5 , Bruno Salaun  5 , Céline Verheust  4 , Marie-Pierre David  4 , Shady Kotb  4 , Veronica Hulstrøm  4
Affiliations
Multicenter Study

Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study

Isabel Leroux-Roels et al. J Infect Dis. .

Abstract

Background: In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 μg RSVPreF3-AS01E formulation.

Methods: In total, 122 older adults (60-80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 μg RSVPreF3 antigen), received an additional 120 μg RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 μg RSVPreF3-AS01E doses until 1 month after dose 3.

Results: Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1.

Conclusions: Revaccination with 120 μg RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults.

Clinical trials registration: NCT04657198; EudraCT, 2020-000692-21.

Keywords: AS01E; RSV neutralizing titers; RSV vaccine; RSVPreF3; cell-mediated immunity; respiratory syncytial virus.

Plain language summary

Respiratory syncytial virus (RSV) is a common, contagious seasonal virus causing respiratory tract infections. In older adults, RSV can cause serious respiratory illnesses or worsen underlying medical conditions such as chronic diseases of the lungs or heart failure. Severe disease may lead to hospitalization, increased need for oxygen, and ventilatory support. However, several vaccines against RSV in older adults have recently been licensed in the United States and European Union. This study evaluated safety and immune responses after revaccination (third dose) with an adjuvanted vaccine against RSV in older adults aged 60–80 years, who had received 2 doses of the vaccine with a similar adjuvanted formulation in a previous (parent) study. Revaccination was done with the licensed vaccine formulation, which was also selected for further investigation in several phase 3 clinical trials. This study found that immune responses against RSV persisted above prevaccination levels for at least 18 months after the second vaccination in the parent study. The third vaccine dose was well tolerated and recalled the immune responses in older adults. Together with the ongoing confirmatory clinical trials, these results help better characterize this RSV vaccine, in terms of safety and RSV-specific immune responses elicited in older adults.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. I. L. R. reports funding from Icosavax and Virometix to her institution for the conduct of RSV vaccine trials, and from GSK to her institution for conduct of this clinical trial. M. V. R. reports GSK funding to the Leuven University Vaccinology Center for the conduct of the clinical trial. C. Vm. reports GSK funding to her institution for the conduct of the clinical trial as at the time of the execution of the clinical trial she was an investigator; C. Vm. joined GSK after the close of the study at her institution and is currently an employee of GSK; however, she does not hold any shares. C. V. A., N. D. S., B. S., C. V., M. P. D., S. K., and V. H. were employees of GSK at the time of the study conduct. N. D. S., B. S., M. P. D., C. V., S. K., and V. H. hold shares from GSK as part of their past/current employee remuneration. All current/previous employees of GSK declare financial and nonfinancial relationships and activities. 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.
Overview of parent and extension study designs. The parent study design and data have been published [18]. Syringe symbols represent vaccination. Time points 0, 1, 2, 3, 8, 14, 20, and 21 indicate study time points at M0 (day 1, dose 1 vaccination), M1 (day 31, 1 month after dose 1), M2 (day 61, dose 2 vaccination), M3 (day 91, 1 month after dose 2), M8, M14, M20 (dose 3 vaccination), and M21 (1 month after dose 3). Participants received 2 doses of the AS01E-adjuvanted vaccine formulation with 30, 60, or 120 μg of RSVPreF3 antigen in the parent study and a third dose of the AS01E-adjuvanted vaccine formulation containing 120 μg of RSVPreF3 antigen in the extension study, indicated by 30/120-, 60/120-, and 120/120 μg RSVPreF3-AS01E. Abbreviations: AS01E, adjuvant system; M, month; RSVPreF3, prefusion conformation of the respiratory syncytial virus fusion (F) protein.
Figure 2.
Figure 2.
Participant flow chart with (A) reasons for withdrawal and elimination from the exposed set and (B) per-protocol set. aParticipant withdrawal (including consent withdrawal) was due to a reason other than an adverse event and/or solicited adverse event, migration from study area, loss to follow-up, or sponsor study termination. Participants received 2 doses of the AS01E-adjuvanted vaccine formulation with 30, 60, or 120 μg of RSVPreF3 antigen in the parent study and a third dose of the AS01E-adjuvanted vaccine formulation containing 120 μg of RSVPreF3 antigen in the extension study, indicated by 30/120-, 60/120-, and 120/120 μg RSVPreF3-AS01E. M20 and M21 indicate study time points at month 20 (dose 3 vaccination) and month 21 (1 month after dose 3) in the extension study. Abbreviations: COVID-19, coronavirus disease 2019; M, month; RSVPreF3, prefusion conformation of the respiratory syncytial virus fusion (F) protein.
Figure 3.
Figure 3.
Percentage of participants reporting (A) at least 1 solicited AE (any, administration-site, and systemic adverse event) within 4 days, or (B) at least 1 solicited administration-site AE within 4 days, or (C) at least 1 unsolicited AE within 30 days after vaccination with the third dose of the 120 μg RSVPreF3-AS01E formulation (exposed set). The only collected systemic AE was fever, which was defined as body temperature ≥38°C (grade 3 fever was defined as temperature >39°C). Grade 3 erythema and swelling were defined as being >100 mm in diameter. No serious AEs, pIMDs, and deaths were reported within 30 days after dose 3. Participants received 2 doses of the AS01E-adjuvanted vaccine formulation with 30, 60, or 120 μg of RSVPreF3 antigen in the parent study and a third dose of the AS01E-adjuvanted vaccine formulation containing 120 μg of RSVPreF3 antigen in the extension study, indicated by 30/120-, 60/120-, and 120/120 μg RSVPreF3-AS01E. Abbreviations: AE, adverse event; AS01E, adjuvant system [18]; CI, confidence interval; RSVPreF3, prefusion conformation of the respiratory syncytial virus fusion (F) protein.
Figure 4.
Figure 4.
Humoral immune responses in terms of RSV-A and RSV-B nAb GMTs (ED60) and RSVPreF3-specific IgG GMCs (ELU/mL) in the 120/120 μg RSVPreF3-AS01E group (per-protocol set). Part of these data (until M14) have been published in the parent study [18]; only data for 120/120 μg RSVPreF3-AS01E formulation were obtained in the present (extension) study. Syringe symbols represent vaccination. Fold increase indicates fold increase in GMT and GMC values at M20 (before dose 3 in extension study) and M21 (1 month after dose 3 in the extension study) compared to M0 (before dose 1 in parent study) as well as GMT and GMC fold increase at M21 compared to M20. Time points 0, 1, 2, 3, 8, and 14 designate M0 (day 1), M1 (day 31), M2 (day 61), M3 (day 91), M8, and M14 in the parent study, respectively. Neutralizing titers against RSV-B were not measured at M2. Data are plotted as mean values with 95% confidence intervals. Participants received 2 doses of the AS01E-adjuvanted vaccine formulation with 120 μg of RSVPreF3 antigen in the parent study and a third dose of the AS01E-adjuvanted vaccine formulation containing 120 μg of RSVPreF3 antigen in the extension study, indicated by 120/120 μg RSVPreF3-AS01E. Abbreviations: AS01E, adjuvant system [18]; ED60, estimated dilution 60; ELU, enzyme-linked immunosorbent assay units; GMC/GMT, geometric mean concentration/titer; IgG, immunoglobulin G; M, month; nAb, neutralizing antibody; RSV-A and RSV-B, respiratory syncytial virus subtypes A and B; RSVPreF3, RSV fusion protein stabilized in its prefusion trimeric conformation.
Figure 5.
Figure 5.
Frequencies of RSVPreF3-specific CD4+ T cells expressing at least (A) 2 markers (among IL-2, CD40L, TNF-α, IFN-γ) or (B) IFN-γ in the 120/120 μg RSVPreF3-AS01E group (per-protocol set). Part of these data (time points to M14) have been published in the parent study [18]. Only data for 120/120 μg RSVPreF3-AS01E formulation were obtained in the present (extension) study. Syringe symbols represent vaccination. The dashed horizontal line represents the assay cutoff value of 590. Fold increase and the corresponding horizontal lines indicate fold increase in frequencies of CD4+ T cells at M20 (before dose 3 in extension study) and M21 (1 month after dose 3 in the extension study) compared to M0 (before dose 1 in parent study), as well as fold increase in frequencies at M21 compared to M20. Time points 0, 1, 2, 3, 8, and 14 designate M0 (day 1, dose 1 vaccination), M1 (day 31, 1 month after dose 1), M2 (day 61, dose 2 vaccination), M3 (day 91, 1 month after dose 2), M8, and M14 in the parent study. Data are plotted as box and whisker plots with a median, interquartile range (Q1 and Q3, first and third quartile), minimum and maximum. Participants received 2 doses of the AS01E-adjuvanted vaccine formulation with 120 μg of RSVPreF3 antigen in the parent study and a third dose of the AS01E-adjuvanted vaccine formulation containing 120 μg of RSVPreF3 antigen in the extension study, indicated by 120/120 μg RSVPreF3-AS01E. Abbreviations: AS01E, adjuvant system [18]; CD4+, cluster-of-differentiation-4-expressing; CD40L, cluster of differentiation 40 ligand; IFN-γ, interferon-γ; IL-2, interleukin 2; M, month; RSVPreF3, respiratory syncytial virus fusion protein stabilized in its prefusion trimeric conformation; TNF-α, tumor necrosis factor-α.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

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. Staadegaard L, Caini S, Wangchuk S, et al. . Defining the seasonality of respiratory syncytial virus around the world: national and subnational surveillance data from 12 countries. Influenza Other Respir Viruses 2021; 15:732–41. - PMC - PubMed
    1. Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev 2017; 30:277–319. - PMC - PubMed
    1. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J of Med 2005; 352:1749–59. - PubMed
    1. Nam HH, Ison MG. Respiratory syncytial virus infection in adults. BMJ 2019; 366:l5021. - PubMed

Publication types

Substances

Associated data