Efficacy and safety of respiratory syncytial virus vaccines

Rationale: Respiratory syncytial virus (RSV) is a highly transmissible pathogen that causes varying degrees of respiratory illness across all age groups. The safety and efficacy profiles of available RSV vaccines, a critical consideration for their integration into public health strategies and clinical practice, remain uncertain.

Objectives: To assess the benefits and harms of RSV vaccines compared to placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or monoclonal antibodies (mAbs) across all human populations.

Search methods: We conducted a comprehensive literature search of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the WHO ICTRP following standard systematic review methodology from 2000 to April 2024.

Eligibility criteria: We included both randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) involving all human populations comparing RSV vaccines with placebo, no intervention, vaccines for other respiratory infections, other RSV vaccines, or mAbs. We excluded studies focused on dose-finding schedules and immunogenicity assessment.

Outcomes: Benefits included frequency of RSV illness (both lower and upper respiratory illness) confirmed by laboratory tests (RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness); hospitalisation due to RSV disease (both lower and upper respiratory illness) confirmed by laboratory tests; mortality from illness caused by RSV (confirmed by laboratory test); all-cause mortality; and admission to an intensive care unit. Harms included serious adverse events (SAEs) related to vaccination, including neurological disorders such as Guillain-Barré syndrome.

Risk of bias: We assessed risk of bias in RCTs using Cochrane's RoB 2 tool.

Synthesis methods: We used standard Cochrane methods.

Included studies: We identified 14 RCTs: five trials (101,825 participants) on older adults; three trials (12,010 participants) on maternal vaccination and effects on infants; one trial (300 participants) on women of childbearing age; and five trials (192 participants) on infants and children. We identified no NRSIs.

Synthesis of results: RSV prefusion vaccine versus placebo in older adults These vaccines reduced RSV-associated lower respiratory tract illness with vaccine efficacy (VE) of 77% (95% confidence interval (CI) 0.70 to 0.83; risk ratio (RR) 0.23, 95% CI 0.17 to 0.30; 4 RCTs, 99,931 participants; high-certainty evidence) and RSV-associated acute respiratory illness with VE of 67% (95% CI 0.60 to 0.73; RR 0.33, 95% CI 0.27 to 0.40; 3 RCTs, 94,339 participants; high-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). RSV postfusion F protein-based vaccine versus placebo in older adults There is probably little to no difference in RSV-associated lower respiratory tract illness with VE of -0.37% (95% CI -1.96 to 0.37; RR 1.37, 95% CI 0.63 to 2.96; 1 RCT, 1894 participants; moderate-certainty evidence) and RSV-associated acute respiratory illness with VE of -0.07% (95% CI -1.15 to 0.47; RR 1.07, 95% CI 0.53 to 2.15; 1 RCT, 1894 participants; moderate-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Maternal RSV F protein-based vaccine versus placebo in infants These vaccines reduced medically attended RSV-associated lower respiratory tract illness with VE of 54% (95% CI 0.28 to 0.71; RR 0.46, 95% CI 0.29 to 0.72; 3 RCTs, 12,010 participants; high-certainty evidence), medically attended RSV-associated severe lower respiratory tract illness with VE of 74% (95% CI 0.44 to 0.88; RR 0.26, 95% CI 0.12 to 0.56; 3 RCTs, 12,010 participants; high-certainty evidence), and hospitalisation due to RSV disease with VE of 54% (95% CI 0.27 to 0.71; RR 0.46, 95% CI 0.29 to 0.73; 2 RCTs, 11,502 participants; high-certainty evidence) in infants. There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination in mothers and infants (low-certainty evidence). Live-attenuated RSV vaccines versus placebo in infants and children The evidence is very uncertain regarding all-cause medically attended acute respiratory illness (MAARI) with VE of 26% (95% CI -0.01 to 0.46; RR 0.74, 95% CI 0.54 to 1.01; 5 RCTs, 171 participants; very low-certainty evidence) and RSV-associated MAARI with VE of 38% (95% CI -0.24 to 0.69; RR 0.62, 95% CI 0.31 to 1.24; 5 RCTs, 192 participants; very low-certainty evidence). There may be little to no difference in SAEs related to vaccination (low-certainty evidence). RSV recombinant F nanoparticle vaccine versus placebo in women of childbearing age The evidence is very uncertain regarding new RSV infections with VE of 50% (95% CI 0.08 to 0.73; RR 0.50, 95% CI 0.27 to 0.92; 1 RCT, 300 participants; very low-certainty evidence). There may be little to no difference in mortality from illness caused by RSV, all-cause mortality, and SAEs related to vaccination (low-certainty evidence). Phase III trials consistently demonstrated low risk of bias. Whilst phase I and II trials occasionally raised concerns about selection bias in the randomisation process, the overall evidence was deemed robust.

Authors' conclusions: RSV prefusion vaccines reduced RSV-associated lower respiratory tract illness and acute respiratory illness in older adults. There may be little to no difference in SAEs related to vaccination in older adults. Maternal vaccination with RSV F protein-based vaccines reduced medically attended RSV-associated lower respiratory tract illness and severe cases in infants. There may be little to no difference in SAEs related to vaccination in mothers and infants. The evidence is very uncertain regarding the effects of RSV vaccine on women of childbearing age, and the effects of live-attenuated RSV vaccines on infants and children; there may be little to no difference in SAEs related to vaccination.

Funding: This review was funded by the EU4Health Programme under a service contract with the European Health and Digital Executive Agency (HaDEA).

Registration: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023439128).

Author/s:

K M Saif-Ur-Rahman, Catherine King, Seán Olann Whelan, Matthew Blair, Seán Donohue, Caoimhe Madden, Kavita Kothari, Isolde Sommer, Thomas Harder, Nicolas Dauby, Ida Rask Moustsen-Helms, Simona Ruta, Julie Frère, Viktoria Schönfeld, Eero Poukka, Irja Lutsar, Kate Olsson, Angeliki Melidou, Karam Adel Ali, Kerry Dwan, Declan Devane

Estimated Vaccine Effectiveness for Respiratory Syncytial Virus-Related Lower Respiratory Tract Disease

Alex Haga — Tue, 17 Dec 2024 19:36:52 +0000

Date Added:

December 17, 2024

Journal/Publication:

JAMA Netw Open

Publication Date:

December 2, 2024

Issue:

Volume:

URL:

Estimated Vaccine Effectiveness for Respiratory Syncytial Virus-Related Lower Respiratory Tract Disease

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2024.50832

Keywords

vaccine efficacy

vaccine

Respiratory

Lower Respiratory Tract Disease

PMID (1):

39671195

MeSH

COVID-19 / epidemiology

Emergency Service

Hospital / statistics & numerical data

Respiratory Syncytial Virus Infections* / epidemiology

Respiratory Tract Infections / epidemiology

Vaccine Efficacy* / statistics & numerical data

Not the strongest methodology but still suggests the RSV vaccine is very effective for reducing RSV-related hospitalizations in people over 75. James W. Mold, MD, MPH

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Importance: Clinical trials have demonstrated high vaccine efficacy (VE) against lower respiratory tract disease (LRTD) but enrolled a smaller proportion of persons aged 75 years or older and those with comorbidities than seen in highest-risk populations in clinical practice settings. Additionally, VE against respiratory syncytial virus (RSV)-related hospitalizations and emergency department (ED) visits is not yet fully described.

Objective: To estimate Respiratory Syncytial Virus Prefusion F (RSVpreF) effectiveness in older adults.

Design, setting, and participants: This was a retrospective case-control study with a test negative design. Cases were adults aged 60 years or older with hospitalizations or ED visits at Kaiser Permanente of Southern California for LRTD from November 24, 2023, to April 9, 2024, who had respiratory swabs collected and tested for RSV. Two control definitions were prespecified: (1) strict controls included RSV-negative LRTD events that were negative for human metapneumovirus, SARS-CoV-2, and influenza, and positive for a nonvaccine preventable cause (primary) and (2) broad controls included all RSV-negative LRTD events (sensitivity analysis). Enhanced specimen collection was conducted to salvage clinical respiratory swabs not tested for RSV during routine care. Data were analyzed from May to September 2024.

Exposure: RSVpreF vaccine receipt during the first RSV season after licensure and 21 or more days before LRTD event.

Main outcomes and measures: Estimated VE against first episode of RSV-related LRTD hospitalization or ED visit.

Results: A total of 7047 LRTD-related hospitalizations or ED encounters with RSV testing results were included. The mean (SD) age was 76.8 (9.6) years; 3819 (54.2%) were female; 839 (11.9%) were non-Hispanic Asian or Pacific Islander, 2323 (33.0%) were Hispanic, 1197 (17.0%) were non-Hispanic Black, and 2602 (36.9%) were non-Hispanic White; 998 (14.2%) were immunocompromised; and 6573 (93.3%) had 1 or more Charlson comorbidity. Using strict controls, estimated adjusted VE was 91% (95% CI, 59%-98%). Using broad controls, estimated adjusted VE was 90% (95% CI, 59%-97%).

Conclusions and relevance: In a high-risk, general population, RSVpreF vaccination conferred protection against RSV-related LRTD in the hospital and ED settings among US adults aged 60 years or older, the majority of whom were aged 75 years or older and had comorbidities. These data support use of this vaccine in older adults.

Author/s:

Sara Y Tartof, Negar Aliabadi, Gabriella Goodwin, Jeff Slezak, Vennis Hong