ABSTRACT

Aerosol biology (aerobiology) as it relates to respiratory viral diseases is an understudied area considering the vast microbiome in the nasopharynx and related upper respiratory tract (URT) airways [1-3]. Despite the abundance of microbes that coexist at mucosal surfaces, comparatively few of these microorganisms are pathogenic with most occupying commensal or opportunistic niches in the URT microbiome. However, several pathogens have evolved airborne transmission as a primary route of infection in part to gain direct access to the respiratory system in order to facilitate host-to-host transmission. One example is inuenza virus, which can be considered an obligate airborne pathogen. Inuenza infection induces host generation of large quantities of virus-laden aerosols via coughs and sneezes that typically serve as a means for virus transmission via the respiratory system. Infectious aerosols

Aerosol Biology .......................................................................................................93 Small Animal Models and Aerosol Transmission ....................................................97 Respiratory Virus Infection ......................................................................................99 Countermeasures for Respiratory Tract Infections ................................................ 101 Inuenza Virus, a Prototypical Respiratory Tract Virus......................................... 103 Controlling Inuenza Virus Disease Burden .......................................................... 105 Brief History of Inuenza Vaccines ....................................................................... 106 Live-Attenuated Inuenza Vaccines ....................................................................... 107 Pulmonary Delivery ............................................................................................... 108 Pulmonary Drug Delivery ...................................................................................... 110 Aerosol Inhalers ..................................................................................................... 113 Safety of Aerosol Vaccines..................................................................................... 114 Benets and Drawbacks of Inhaled Agents ........................................................... 116 Considerations ........................................................................................................ 117 Summary ................................................................................................................ 118 References .............................................................................................................. 119

produced by the affected host typically range in size from 0.1 to 20 μm [3]. Aerosol generation induced by a pathogen is one way to efciently enable multiple passages through several hosts, an effect that may ultimately lead to a general increase in relative virulence via virus modications induced by passaging in successive hosts. Aerosols generated during infection vary in both droplet size and virus content; that is, those larger than 5 μm in diameter are classied as droplets (and have a relatively low virus content), while those smaller than 5 μm are classied as particles and typically have increased virus content [4,5].