Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus

Abstract

Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate.

Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms

“…Histopathological changes in the stained lung tissue sections were scored by a veterinary pathologist blinded to the treatment group. Lung histopathology was scored using five parameters (necrosis of the bronchiolar epithelium, airway inflammation, perivascular/bronchiolar cuffing, alveolar exudates and septal inflammation) scored on a 5-point scale of 0 to 4 and then summed to give a total slide score ranging from 0 to 20 per slide and a total animal score from 0 to 60 44 . The slides were also scored using the “Iowa” method, that also takes into account the amount of viral antigen present in the sample, as described 45 .…”

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

“…The slides were fixed with 2 drops of acrytol (Leica, Concord, ON, Canada) with a coverslip and scored at ϫ10 and ϫ100 magnification. The slides were scored blinded, and the scoring system evaluated the following 5 parameters: (i) airway epithelial necrosis, attenuation, or disruption; (ii) airway inflammation; (iii) peribronchiolar and perivascular lymphocytic cuffing; (iv) alveolar cellular exudate/edema and interlobular edema; and (v) alveolar septal inflammatory cells and cellularity (41). Each parameter was scored from 0 to 4 for a total possible score of 20 ( Table 2).…”

A single cycle influenza virus coated in H7 hemagglutinin provides heterotypic protection and neutralising antibody responses to both glycoproteins

“…We have shown that in ferrets immunization with H1N1 or H5N1 S-FLU (group 1) significantly reduced replication of H1N1, H6N1, H5N1 (group 1) and H7N9 (group 2) wild-type viruses in the lung [44]. In pigs, immunization with H1N1 or H5N1 S-FLU reduced virus titres in nasal swabs and lungs following challenge with a swine H1N1pdm09 isolate and [45]. S-FLU can infect cells for one round only, but this is sufficient to express all the conserved virus proteins in the cytosol for induction of a vigorous local CD8 T cell response.…”