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Abstract Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies. Animals infected with higher doses of virus also experienced increasing severity of clinical symptoms and fever at 2 days post-infection (DPI). Interestingly, weight loss was more pronounced in animals infected with lower doses of virus compared to those infected with a higher dose; these results were consistent with viral titers of swabs collected from the nares, but not the throat. Analyzed specimens included nasal and throat swabs from 1, 3, 5, and 7 DPI as well as tissue samples from caudal lung and nasal turbinates. Viral titers of the swab samples in all groups were higher on 1 and 3 DPI and returned to baseline levels by 7 DPI. Analysis of nasal turbinates indicated presence of virus at 3 DPI in all infected groups, whereas virus was only detected in the lungs of animals in the two highest dose groups. Histological analysis of the lungs showed a range of pathology, such as chronic inflammation and bronchial epithelial hypertrophy. The results provided here offer important endpoints for preclinical testing of the efficacy of new antiviral compounds and experimental vaccines.

Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies. Animals infected with higher doses of virus also experienced increasing severity of clinical symptoms and fever at 2 days post-infection (DPI). Interestingly, weight loss was more pronounced in animals infected with lower doses of virus compared to those infected with a higher dose; these results were consistent with viral titers of swabs collected from the nares, but not the throat. Analyzed specimens included nasal and throat swabs from 1, 3, 5, and 7 DPI as well as tissue samples from caudal lung and nasal turbinates. Viral titers of the swab samples in all groups were higher on 1 and 3 DPI and returned to baseline levels by 7 DPI. Analysis of nasal turbinates indicated presence of virus at 3 DPI in all infected groups, whereas virus was only detected in the lungs of animals in the two highest dose groups. Histological analysis of the lungs showed a range of pathology, such as chronic inflammation and bronchial epithelial hypertrophy. The results provided here offer important endpoints for preclinical testing of the efficacy of new antiviral compounds and experimental vaccines. [ABSTRACT FROM AUTHOR]

Death by respiratory complications from influenza infections continues to be a major global health concern. Antiviral drugs are widely available for therapy and prophylaxis, but viral mutations have resulted in resistance that threatens to reduce the long-term utility of approved antivirals. Vaccination is the best method for controlling influenza, but vaccine strategies are blunted by virus antigenic drift and shift. Genetic shift in particular has led to four pandemics in the last century, which have prompted the development of efficient global surveillance and vaccination programs. Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. Recently, a novel H7N9 avian influenza virus with potential to become a pandemic strain emerged in China and was transmitted from animals to humans with a demonstrated >20% mortality rate. Sporadic outbreaks of highly lethal avian virus strains have already increased public awareness and altered annual vaccine production strategies to prevent the natural adaption of this virus to human-to-human transmission. Additional strategies for combating influenza include advancement of new antivirals for unexploited viral or host cellular targets; novel adjuvants and alternate vaccine delivery systems; and development of universal protein, DNA, or multivalent vaccines designed to increase immune responsiveness and enhance public health response times.