Delivery of a thermo-enzymatically treated influenza vaccine using pulmonary surfactant in pigs

Swine influenza A virus (IAV-S) infections are a major cause of economic losses for the swine industry. The vast genetic and antigenic diversity often results in mismatch between the vaccine and field strains, necessitating frequent updates of vaccines. Inactivated IAV-S vaccines are of questionable efficacy. Intra-nasally administered live vaccines are more effective but are associated with safety concerns. The objective of this study was to develop a first-generation vaccine which combines the safety and efficacy advantages of inactivated and attenuated vaccines respectively. The approach targeted fragmentation of viral nucleic acids while preserving structure. Hence, cultures of influenza A/CA/04/09 H1N1 were exposed to 44 °C for 10 min. to reversibly denature the capsid, followed by RNase treatment to digest the genomic RNA and then refolded at lower temperatures. As targeted, treated virions retained an intact structure and were not detected in the first passage in infected cells. To improve intra-nasal delivery of the vaccine antigen, the vaccine antigen was delivered in porcine lung surfactant. Both the treated vaccine alone or vaccine in combination with the surfactant elicited strong anti-HA and virus neutralizing antibodies, protection against viral shedding and lung lesions in 3-week-old piglets. There were no significant differences between the groups. Vaccine viral replication was not detected in the vaccinated pigs. The described approach can advance current immunization practices against swine influenza viruses due to the relative simplicity, high efficacy and safety and ease of adaptation to newly emerging field strains.