Aerosol Exposure of Monkeys to Influenza Virus.

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Abstract
Discussion and summary Previous studies from this laboratory(1) showed that intratracheal inoculation of rhesus monkeys with the PR8 strain of influenza virus resulted in mild illness in 2 of 4 monkeys; after intranasal inoculation, no clinical signs of illness were observed. Results of studies by others (2–5) have varied with the influenza virus strain and monkey species employed. In all, virus was administered intratracheally or intranasally, and in general, clinical evidence of disease was minimal or absent. The development of quantitative procedures for exposure of experimental animals to aerosols of infective organisms(6) suggested reinvestigation of the response of monkeys following challenge with influenza virus by these methods. The present report describes the clinical, hematologic and serologic response of rhesus and cynomolgus monkeys after aerosol exposure to the PR8 strain of influenza virus. Materials and methods. Challenge of young adult monkeys, Macaca mulatta and M. irus, was conducted in a Model 3 Henderson apparatus(6) by previously described methods (7,8). The aerosol generator was charged with mouse lung nitrate containing about 1.0 × 108 mouse intranasal LD50 per ml of the PR8 strain of influenza A virus. Monkey doses were calculated from studies of concurrently exposed 14–16 g white mice. Intratracheal inoculation of allantoic fluids(9) containing strains A/PR8/34, Swine/1976/31, A2/Japan/305/57, and B/Great Lakes/1739/54 was performed as described previously(1). Physical examinations, hematologic and serologic studies were carried out for 2 weeks prior to challenge. After challenge, monkeys were examined twice daily. Femoral vein blood was used for blood counts and C-reactive protein (CRP) tests daily or every other day, and weekly for serologic studies.