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Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations., Author summary Antibodies (Ab) are increasingly used to treat human infectious diseases. Pigs are large animals, natural hosts for influenza viruses and very similar to humans. We generated monoclonal Abs from influenza infected pigs and show that they recognize the same sites of the virus as humans. One of these sites was not recognized by ferret anti-sera, which are commonly used to predict the evolution of the virus and inform vaccine design. We also show that prophylactic administration of one of these mAb to pigs abolished lung viral load and prevented lung damage following infection with influenza. We conclude that the pig is a useful model to test how best to use Abs for therapy and to inform vaccine recommendations for humans.

Influenza is a major cause of mortality and morbidity worldwide. Despite numerous studies of the pathogenesis of influenza in humans and animal models the dynamics of infection and transmission in individual hosts remain poorly characterized. In this study, we experimentally modelled transmission using the H1N1pdm09 influenza A virus in pigs, which are considered a good model for influenza infection in humans. Using an experimental design that allowed us to observe individual transmission events occurring within an 18-hr period, we quantified the relationships between infectiousness, shed virus titre and antibody titre. Transmission event was observed on 60% of occasions when virus was detected in donor pig nasal swabs and transmission was more likely when donor pigs shed more virus. This led to the true infectious period (mean 3.9 days) being slightly shorter than that predicted by detection of virus (mean 4.5 days). The generation time of infection (which determines the rate of epidemic spread) was estimated for the first time in pigs at a mean of 4.6 days. We also found that the latent period of the contact pig was longer when they had been exposed to smaller amount of shed virus. Our study provides quantitative information on the time lines of infection and the dynamics of transmission that are key parts of the evidence base needed to understand the spread of influenza viruses though animal populations and, potentially, in humans., Author summary Influenza is a major cause of mortality and morbidity worldwide. The relationship between the time course of influenza infection and virus shedding and onward transmission of the virus remains poorly characterized. Pigs are a natural host for influenza infection with shedding patterns similar to humans. Therefore we experimentally infected pigs with the H1N1pdm09 influenza A virus using direct contact challenge and then mixed the infected pigs with a different naïve pig each day to understand when transmission occurred. Using mathematical modeling, we found that transmission events occurred on 60% of occasions when the infected pigs were shedding virus and that the risk of transmission increased with the quantity of virus shed. Also it was clear the incontact pigs started to shed virus later after exposure when the infected pigs were shedding low quantities of virus. Our study therefore provides quantitative information on the time lines of influenza virus infection and the dynamics of transmission. This is important to understand the spread of influenza viruses through animal populations and, potentially, in humans.

Hepatitis E is an important public health disease [1]. Although the mortality rate is less than 1% in the general population, it can reach up to 25% in infected pregnant women. According to the World Health Organization, each year an estimated 20 million infections occur worldwide resulting in >3 million symptomatic cases and 56,600 hepatitis E-related deaths (http://www.who.int/mediacentre/factsheets/fs280/en/). Large explosive waterborne outbreaks of hepatitis E are generally seen in developing countries with poor sanitation conditions, whereas in industrialized countries, sporadic and cluster cases of hepatitis E have been reported. Hepatitis E is a self-limiting acute disease that normally does not go into chronicity. However, recently, chronic hepatitis E has become a significant clinical problem in immunocompromised individuals such as organ transplant recipients [2]. The discovery of animal strains of hepatitis E virus (HEV) [3] that infect across species barriers revolutionizes the way we used to think about this important disease. Hepatitis E is now recognized as a zoonotic disease, and animal reservoirs exist [4]. Herein, I briefly discuss the ever-expanding host ranges, cross-species infection, zoonotic risk, and food safety of HEV. The author's research on HEV is supported by the National Institutes of Health (R01AI074667 and R01AI050611). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.