Effective Aerosol Inoculation of Dose-Escalated Seasonal Influenza H3N2 Virus in Controlled Human Infection Model rouphael2025effective

Dose-escalation controlled human infection study (Feb 2024–Mar 2025) evaluating aerosolized inoculation of influenza A/Perth/16/2009 (H3N2) using two devices (FMAG and a medical nebulizer) in 14 healthy adults (aged 18–49). Participants were challenged in an inpatient unit and monitored daily; molecular (qPCR) and infectious (plaque assay) viral loads were measured at multiple upper airway sites (nasopharynx, anterior nares, buccal, oropharynx, saliva). Study assessed viral shedding kinetics, symptom development (MMID), safety, and seroconversion.

Analytes

nasopharyngeal_gc_ml

Quantitative molecular detection of influenza viral RNA from nasopharyngeal swab samples by RT-PCR, reported as gene copies per mL (gc/mL).

observations for nasopharyngeal_gc_ml

Measurements only — no shedding model is fitted to this analyte, usually because it is sampled once per participant, leaving no trajectory to fit, or because nothing was ever detected. Open triangles are non-detects, drawn at the assay's censoring limit. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: nasopharyngeal swab
Units: gc/mL
Participants: 8
Negative samples: 23
Positive samples (not quantifiable): 0
Quantifiable samples: 33
Limit of quantification: unknown
Limit of detection: 501.1872

anterior_nasal_gc_ml

Quantitative molecular detection of influenza viral RNA from anterior nasal (anterior nares) swab samples by RT-PCR, reported as gene copies per mL (gc/mL).

observations for anterior_nasal_gc_ml

Measurements only — no shedding model is fitted to this analyte, usually because it is sampled once per participant, leaving no trajectory to fit, or because nothing was ever detected. Open triangles are non-detects, drawn at the assay's censoring limit. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: anterior nares swab
Units: gc/mL
Participants: 8
Negative samples: 29
Positive samples (not quantifiable): 0
Quantifiable samples: 27
Limit of quantification: unknown
Limit of detection: 501.1872

buccal_gc_ml

Quantitative molecular detection of influenza viral RNA from buccal swab samples (inner cheek) by RT-PCR, reported as gene copies per mL (gc/mL).

exponential for buccal_gc_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: buccal swab
Units: gc/mL
Participants: 8
Negative samples: 49
Positive samples (not quantifiable): 0
Quantifiable samples: 7
Limit of quantification: unknown
Limit of detection: 501.1872

oropharyngeal_gc_ml

Quantitative molecular detection of influenza viral RNA from oropharyngeal swab samples by RT-PCR, reported as gene copies per mL (gc/mL).

gamma for oropharyngeal_gc_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: oropharyngeal swab
Units: gc/mL
Participants: 8
Negative samples: 31
Positive samples (not quantifiable): 0
Quantifiable samples: 25
Limit of quantification: unknown
Limit of detection: 501.1872

saliva_gc_ml

Quantitative molecular detection of influenza viral RNA from saliva samples by RT-PCR, reported as gene copies per mL (gc/mL).

exponential for saliva_gc_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: saliva
Units: gc/mL
Participants: 8
Negative samples: 29
Positive samples (not quantifiable): 0
Quantifiable samples: 27
Limit of quantification: unknown
Limit of detection: 501.1872

nasopharyngeal_pfu_ml

Infectious virus quantification by plaque assay from nasopharyngeal swab samples, reported as plaque-forming units per mL (pfu/mL).

observations for nasopharyngeal_pfu_ml

Measurements only — no shedding model is fitted to this analyte, usually because it is sampled once per participant, leaving no trajectory to fit, or because nothing was ever detected. Open triangles are non-detects, drawn at the assay's censoring limit. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: nasopharyngeal swab
Units: pfu/mL
Participants: 6
Negative samples: 19
Positive samples (not quantifiable): 0
Quantifiable samples: 23
Limit of quantification: unknown
Limit of detection: 5

anterior_nasal_pfu_ml

Infectious virus quantification by plaque assay from anterior nasal (anterior nares) swab samples, reported as plaque-forming units per mL (pfu/mL).

exponential for anterior_nasal_pfu_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: anterior nares swab
Units: pfu/mL
Participants: 6
Negative samples: 22
Positive samples (not quantifiable): 0
Quantifiable samples: 20
Limit of quantification: unknown
Limit of detection: 5

buccal_pfu_ml

Infectious virus quantification by plaque assay from buccal swab samples, reported as plaque-forming units per mL (pfu/mL).

exponential for buccal_pfu_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: buccal swab
Units: pfu/mL
Participants: 6
Negative samples: 38
Positive samples (not quantifiable): 0
Quantifiable samples: 4
Limit of quantification: unknown
Limit of detection: 5

oropharyngeal_pfu_ml

Infectious virus quantification by plaque assay from oropharyngeal swab samples, reported as plaque-forming units per mL (pfu/mL).

observations for oropharyngeal_pfu_ml

Measurements only — no shedding model is fitted to this analyte, usually because it is sampled once per participant, leaving no trajectory to fit, or because nothing was ever detected. Open triangles are non-detects, drawn at the assay's censoring limit. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: oropharyngeal swab
Units: pfu/mL
Participants: 6
Negative samples: 24
Positive samples (not quantifiable): 0
Quantifiable samples: 18
Limit of quantification: unknown
Limit of detection: 5

saliva_pfu_ml

Infectious virus quantification by plaque assay from saliva samples, reported as plaque-forming units per mL (pfu/mL).

exponential for saliva_pfu_ml

Fitted by censored maximum likelihood. The red line is the median individual; the shaded region is the full range of a simulated cohort drawn from the fitted population, so it shows what simulating from this dataset would produce rather than a confidence interval, with dashed lines at the central 95%. Open triangles are non-detects, drawn at the censoring limit and entering the fit as "below this value" rather than being dropped. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: saliva
Units: pfu/mL
Participants: 6
Negative samples: 24
Positive samples (not quantifiable): 0
Quantifiable samples: 18
Limit of quantification: unknown
Limit of detection: 5

nasopharyngeal_ct

RT-PCR cycle threshold (Ct) values from nasopharyngeal swab samples for influenza viral detection (unit: cycle threshold).

observations for nasopharyngeal_ct

Measurements only — no shedding model is fitted to this analyte, usually because it is sampled once per participant, leaving no trajectory to fit, or because nothing was ever detected. Open triangles are non-detects, drawn at the assay's censoring limit. See the modelling methods for what these estimates do and do not support.

Biomarker: influenza
Specimen: nasopharyngeal swab
Units: cycle threshold
Participants: 6
Negative samples: 7
Positive samples (not quantifiable): 0
Quantifiable samples: 35
Limit of quantification: unknown
Limit of detection: unknown