Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model

<div><p>Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids and reduced macroscopic and microscopic lesions whereas intranasal vaccination with experimental M2e epitope-based subunit vaccines did not. The results further highlight the importance using IAV-S type specific vaccines in pigs.</p></div

Modeling Nasal Physiology Changes Due to Septal Perforations

OBJECTIVE: To use computational fluid dynamics (CFD) technology to help providers understand 1) how septal perforations may alter nasal physiology and 2) how these alterations are influenced by perforation size and location. STUDY DESIGN: Computer simulation study SETTING: Facial Plastic and Reconstructive Surgery clinic SUBJECTS AND METHODS: With the aid of medical imaging and modeling software, septal perforations of 1 and 2 cm in anterior, posterior, and superior locations were virtually created in a nasal cavity digital model. CFD techniques were used to analyze airflow, nasal resistance, air conditioning, and wall shear stress. RESULTS: Bilateral nasal resistance was not significantly altered by a septal perforation. Airflow allocation changed, with more air flowing through the lower-resistance nasal cavity. This effect was greater for anterior and posterior perforations than for the superior location. At the perforation sites, there was less localized heat and moisture flux and wall shear stress in superior perforations compared to those in anterior or posterior locations. For anterior perforations, a larger size produced higher wall shear and velocity, while in posterior perforations a smaller size produced higher wall shear and velocity. CONCLUSIONS: Septal perforations may alter nasal physiology. In the subject studied, airflow allocation to each side was changed as air was shunted through the perforation to the lower-resistance nasal cavity. Anterior and posterior perforations caused larger effects than those in a superior location. Increasing the size of anterior perforations and decreasing the size of posterior perforations enhanced alterations in wall shear and velocity at the perforation