tetano
Editor, Senior Moderator
J Infect Dis
. 2025 Dec 16:jiaf603.
doi: 10.1093/infdis/jiaf603. Online ahead of print. Feasibility and Safety of Aerosolized Influenza Virus Challenge in Humans Using Two Modern Delivery Systems
Nadine Rouphael[SUP] 1 [/SUP], Ralph Tanios[SUP] 1 [/SUP], Jessica Traenkner[SUP] 1 [/SUP], Matthew D Pauly[SUP] 2 [/SUP], Nishit Shetty[SUP] 3 [/SUP], Meredith J Shephard[SUP] 2 [/SUP], A J Campbell[SUP] 2 [/SUP], Christelle Radi[SUP] 1 [/SUP], Shamika Danzy[SUP] 2 [/SUP], Jin Pan[SUP] 4 [/SUP], Andrew P Catchpole[SUP] 5 [/SUP], Alex Mann[SUP] 5 [/SUP], Joshua F Detelich[SUP] 6 [/SUP], Anice C Lowen[SUP] 2 [/SUP], Linsey C Marr[SUP] 7 [/SUP], Seema S Lakdawala[SUP] 2 [/SUP]; Flu CHIM Study Group
Collaborators, Affiliations
Background: Controlled human infection models are widely used to study infectious diseases. Since the 1960s, these studies have primarily relied on intranasal inoculation, as earlier aerosol-based methods raised safety concerns and were largely abandoned despite better mimicking the natural route of infection.
Methods: Utilizing modern advances in aerosol delivery, we conducted a dose-escalation study to evaluate the safety and feasibility of aerosol inoculation for human influenza challenge. Healthy adults aged 18-49 years were inoculated with influenza A/Perth/16/2009 (H3N2) using either a flow-focusing monodisperse aerosol generator (FMAG) delivering coarse particles or a medical nebulizer delivering fine particles. Participants were monitored in a controlled inpatient setting with symptom tracking, virologic sampling, and serology. Doses were escalated according to predefined safety and attack rate thresholds.
Results: Fourteen participants were enrolled. Flow-focusing monodisperse aerosol generator delivery at higher dose levels resulted in infection in 75% of participants (3/4), while nebulizer delivery produced infection in 50% (2/4). Illnesses were mild and self-limited. Viral shedding was detected at multiple respiratory sites, and adverse events were infrequent and generally mild. No serious adverse events occurred. Antibody responses were observed in a subset of infected participants.
Conclusions: In this small pilot, aerosolized challenge using modern delivery systems was feasible under controlled conditions; no safety concerns were identified, and MMID was induced in a subset of participants. These data establish a methodological framework for future studies evaluating pathogenesis and mucosal immune responses to a variety of respiratory pathogens.
Keywords: aerosol inoculation; controlled human infection model; flow-focusing monodisperse aerosol generator; influenza A (H3N2); nebulizer.
. 2025 Dec 16:jiaf603.
doi: 10.1093/infdis/jiaf603. Online ahead of print. Feasibility and Safety of Aerosolized Influenza Virus Challenge in Humans Using Two Modern Delivery Systems
Nadine Rouphael[SUP] 1 [/SUP], Ralph Tanios[SUP] 1 [/SUP], Jessica Traenkner[SUP] 1 [/SUP], Matthew D Pauly[SUP] 2 [/SUP], Nishit Shetty[SUP] 3 [/SUP], Meredith J Shephard[SUP] 2 [/SUP], A J Campbell[SUP] 2 [/SUP], Christelle Radi[SUP] 1 [/SUP], Shamika Danzy[SUP] 2 [/SUP], Jin Pan[SUP] 4 [/SUP], Andrew P Catchpole[SUP] 5 [/SUP], Alex Mann[SUP] 5 [/SUP], Joshua F Detelich[SUP] 6 [/SUP], Anice C Lowen[SUP] 2 [/SUP], Linsey C Marr[SUP] 7 [/SUP], Seema S Lakdawala[SUP] 2 [/SUP]; Flu CHIM Study Group
Collaborators, Affiliations
- PMID: 41400368
- DOI: 10.1093/infdis/jiaf603
Background: Controlled human infection models are widely used to study infectious diseases. Since the 1960s, these studies have primarily relied on intranasal inoculation, as earlier aerosol-based methods raised safety concerns and were largely abandoned despite better mimicking the natural route of infection.
Methods: Utilizing modern advances in aerosol delivery, we conducted a dose-escalation study to evaluate the safety and feasibility of aerosol inoculation for human influenza challenge. Healthy adults aged 18-49 years were inoculated with influenza A/Perth/16/2009 (H3N2) using either a flow-focusing monodisperse aerosol generator (FMAG) delivering coarse particles or a medical nebulizer delivering fine particles. Participants were monitored in a controlled inpatient setting with symptom tracking, virologic sampling, and serology. Doses were escalated according to predefined safety and attack rate thresholds.
Results: Fourteen participants were enrolled. Flow-focusing monodisperse aerosol generator delivery at higher dose levels resulted in infection in 75% of participants (3/4), while nebulizer delivery produced infection in 50% (2/4). Illnesses were mild and self-limited. Viral shedding was detected at multiple respiratory sites, and adverse events were infrequent and generally mild. No serious adverse events occurred. Antibody responses were observed in a subset of infected participants.
Conclusions: In this small pilot, aerosolized challenge using modern delivery systems was feasible under controlled conditions; no safety concerns were identified, and MMID was induced in a subset of participants. These data establish a methodological framework for future studies evaluating pathogenesis and mucosal immune responses to a variety of respiratory pathogens.
Keywords: aerosol inoculation; controlled human infection model; flow-focusing monodisperse aerosol generator; influenza A (H3N2); nebulizer.