Influenza virus infection and aerosol shedding kinetics in a controlled human infection model

• Published in: Journal of virology 2024-11, Vol.98 (12), p.e0161224
• Main Authors: Shetty, Nishit, Shephard, Meredith J, Rockey, Nicole C, Macenczak, Hollie, Traenkner, Jessica, Danzy, Shamika, Vargas-Maldonado, Nahara, Arts, Peter J, Le Sage, Valerie, Anderson, Evan J, Lyon, G Marshall, Fitts, Eric Charles, Gulick, Dalia A, Mehta, Aneesh K, El-Chami, Mikhael F, Kraft, Colleen S, Wigginton, Krista R, Lowen, Anice C, Marr, Linsey C, Rouphael, Nadine G, Lakdawala, Seema S
• Format: Article
• Language: English
• Subjects: Adult; Aerosols; Antibodies, Viral - blood; Editor’s Pick; Feces - virology; Female; Humans; Influenza A Virus, H3N2 Subtype - physiology; Influenza, Human - transmission; Influenza, Human - virology; Kinetics; Male; Middle Aged; Nasopharynx - virology; Pathogenesis and Immunity; RNA, Viral; Saliva - virology; Viral Load; Virology; Virus Shedding; Young Adult
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/jvi.01612-24

Establishing effective mitigation strategies to reduce the spread of influenza virus requires an improved understanding of the mechanisms of transmission. We evaluated the use of a controlled human infection model using an H3N2 seasonal influenza virus to study critical aspects of transmission, including symptom progression and the dynamics of virus shedding. Eight volunteers were challenged with influenza A/Perth/16/2009 (H3N2) virus between July and September 2022 at Emory University Hospital. Viral shedding in the nasopharynx, saliva, stool, urine, and respiratory aerosols was monitored over the quarantine period, and symptoms were tracked until day 15. In addition, environmental swabs were collected from participant rooms to examine fomite contamination, and participant sera were collected to assess seroconversion by hemagglutination inhibition or microneutralization assays. Among the eight participants, influenza virus infection was confirmed in six (75%). Infectious virus or viral RNA was found in multiple physiological compartments, fecal samples, aerosol particles, and on surfaces in the immediate environment. Illness was moderate, with upper respiratory symptoms dominating. In participants with the highest viral loads, antibody titers rose by day 15 post-inoculation, while in participants with low or undetectable viral loads, there was little or no increase in functional antibody titers. These data demonstrate the safety and utility of the human infection model to study features critical to influenza virus transmission dynamics in a controlled manner and will inform the design of future challenge studies focused on modeling and limiting transmission.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05332899. We use a controlled human infection model to assess respiratory and aerosol shedding kinetics to expand our knowledge of influenza infection dynamics and help inform future studies aimed at understanding human-to-human transmission.