Controlled Human Infection Challenge Studies with RSV

Dayananda, Pete; Chiu, Christopher; Openshaw, Peter

doi:10.1007/82_2022_257

Cited by 4 publications

(3 citation statements)

References 107 publications

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“…To our knowledge, this is the first report describing a shift in functional profiles of T cells over the course of a natural RSV infection. T-cell engagement during the course of infection suggested a role of the cellular adaptive immunity in controlling infection, in agreement with observations from experimental RSV challenge models ( 13 ).…”

Section: Discussionsupporting

confidence: 86%

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

Salaun,

De Smedt,

Vernhes

et al. 2023

Front. Immunol.

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IntroductionThe immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.MethodsThis study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017–2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated–) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.ResultsPre–RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).ConclusionThe evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.

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Section: Discussionsupporting

confidence: 86%

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

Salaun,

De Smedt,

Vernhes

et al. 2023

Front. Immunol.

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“…These values were not reproduced in the efficacy study reported here. The RSV controlled human challenge trials have inherent limitations due to the use of highly attenuated RSV strains causing mild to moderate upper respiratory tract disease; such studies can reveal the protective potential of a vaccine, though their results cannot be directly reflective of larger vaccine efficacy studies or real-world analysis [33]. The results of the MVA-BN-RSV challenge trial are nevertheless coherent with the efficacy estimated against ARD and milder LRTD with at least 2 symptoms, but do not align with the efficacy seen against more severe LRTD.…”

Section: Discussionmentioning

confidence: 99%

A multivalent RSV vaccine based on the Modified Vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a Phase 3 clinical study

Jordan,

Jenkins,

Silbernagl

et al. 2024

Preprint

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Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV. Adults aged ≥ 60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022-2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with >=3 and >=2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post vaccination respectively, and SAEs for the entire study period. In total, 18348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9% (95% CI: -16.1; 71.9) against RSV-associated LRTD with >=3 symptoms, 59.0% (95% CI: 34.7; 74.3) against LRTD with >= 2 symptoms, and 48.8% (95% CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with >=3 symptoms since the lower bound of the 95% CI was below 20%, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified. MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.

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“…(2) Develop a set of best practices for using a CHIM in coronavirus vaccine research, to include risk-mitigation strategies [85] . Prior experience with CHIM models for other viral respiratory pathogens, such as influenza virus and respiratory syncytial virus can inform this activity [95] , [96] . (3) Establish parameters, in coordination with global regulators, for using CHIM studies and immunobridging for licensure of candidate vaccines, which has been considered for other pathogens [97] .…”

Section: Introductionmentioning

confidence: 99%

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy

Moore¹,

Leighton²,

Ostrowsky³

et al. 2023

Vaccine

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Controlled Human Infection Challenge Studies with RSV

Cited by 4 publications

References 107 publications

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

A multivalent RSV vaccine based on the Modified Vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a Phase 3 clinical study

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy

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