Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

Nasal high flow nebulization in infants and toddlers: An in vitro and in vivo scintigraphic study.

Aerosol therapy in infants and toddlers is challenging. Nebulization within a nasal high flow (NHF) circuit is attractive. The aim of this study was to quantify aerosol lung deposition when combined with NHF as compared with standard practice. Lung doses were measured scintigraphically after nebulization with jet and mesh nebulizer placed within a NHF circuit in a spontaneously breathing non-human primate model (macaque) and in the anatomical bench SAINT model, respectively representing a full-term newborn and a 9-month-old toddler. In the SAINT model, lung depositions observed with the mesh nebulizer placed in the NHF circuit set at 2 and 4 L/min were 3.3% and 4.2% of the nebulizer charge, respectively, and similar to the 1.70% observed with the control standard facemask jet nebulization (6 L/min flow). In the macaque model, the depositions observed with the mesh nebulizer in the NHF circuit set at 2 and 4 L/min were 0.49% and 0.85%, respectively, also similar to the control measurement (0.71%). Mesh nebulization within a NHF circuit set at 8 L/min and jet nebulization either within a NHF circuit or placed on top of the cannula (NHF set at 2 L/min; total flow of 8 L/min), resulted in a significantly lower lung depositions. Mesh nebulization within a NHF circuit delivering up to 4 L/min gas is likely to be at least as effective than jet nebulization with a facemask in infants and toddlers. Aerosol facemask placement on top of cannulas or jet nebulization within the NHF circuit may be less effective. Pediatr Pulmonol. 2017;52:337-344. © 2016 Wiley Periodicals, Inc.