Controlled human infection with RSV: The opportunities of experimental challenge

Habibi, Maximillian S.; Chiu, Christopher

doi:10.1016/j.vaccine.2016.08.086

Cited by 21 publications

(13 citation statements)

References 45 publications

(58 reference statements)

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“…Our study showed an upregulation of multiple interferon regulated genes in whole blood from infants with RSV infection indicating that the induction of Siglec‐1 during RSV infection could be dependent on type I IFNs. Human experimental RSV infection models in adults have been performed 24 and could be used to confirm our results derived from RSV‐infected infants. Whole blood gene expression may not accurately reflect the inflammatory response at the site of infection but rather reflect inflammation in general.…”

Section: Discussionsupporting

confidence: 62%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

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Section: Discussionsupporting

confidence: 62%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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“…The promising data obtained allow the further development of T cell-based RSV vaccines by incorporating human RSV epitopes into the LAIV genome. RSV human challenge models will help to accelerate this vaccine development (Habibi and Chiu, 2017). In particular, new data are emerging regarding RSV epitopes for CD4 airway-resident T cells (Guvenel et al, 2020) and CD8 resident memory T cells (Jozwik et al, 2015) with a defined immunodominance hierarchy.…”

Section: Discussionmentioning

confidence: 99%

Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

et al. 2020

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“…However, no two challenges will be identical, depending on how the swab is rolled over the unique contours of each pharynx and how the procedure is tolerated. Alternative methods discussed included intranasal injection as in the non-human primate GAS nasopharyngitis model [47] and HIS for other respiratory pathogens [53][54][55][56]. The record of successful and safe induction of experimental pharyngitis in the 1970s was ultimately decisive in choosing the swab method.…”

Section: Discussionmentioning

confidence: 99%

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study

Osowicki

Azzopardi

Baker

et al. 2019

Vaccine

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Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a diverse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease. We review the small number of historical GAS HIS and present the study protocol for a dose-ranging inpatient study in healthy adults. The primary objective of the study is to establish a new GAS pharyngitis HIS with an attack rate of at least 60% as a safe and reliable platform for vaccine evaluation and pathogenesis research. According to an adaptive dose-ranging study design, emm75 GAS doses manufactured in keeping with principles of Good Manufacturing Practice will be directly applied by swab to the pharynx of carefully screened healthy adult volunteers at low risk of severe complicated GAS disease. Participants will remain as closely monitored inpatients for up to six days, observed for development of the primary outcome of acute symptomatic pharyngitis, as defined by clinical and microbiological criteria. All participants will be treated with antibiotics and followed as outpatients for six months. An intensive sampling schedule will facilitate extensive studies of host and organism dynamics during experimental pharyngitis. Ethics approval has been obtained and the study has been registered at ClinicalTrials.gov (NCT03361163).

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Controlled human infection with RSV: The opportunities of experimental challenge

Cited by 21 publications

References 45 publications

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study

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