Influenza A virus – swine (IAV-S), commonly also known as swine influenza virus (SIV), is the cause of acute, severe respiratory disease in pigs and is considered one of the top three health challenges facing the swine industry in the United States (U.S.). In addition, IAV-S is a zoonotic pathogen readily shared between pigs and people, representing a health and economic threat to humans and swine worldwide. Morbidity from swine influenza in a pig population may achieve 100% with low mortality, although secondary bacterial infections may increase the death loss. However, IAV-S decreases growth and production as well as increasing treatment costs leading to further economic losses. Estimates have shown a reduction of $10.31 per market hog per year due to influenza virus infections. To put this into perspective, a large production system in the U.S. may sustain losses of over $65 million per year due to IAV and its associated costs. In addition, the increased use of antibiotics to treat secondary infections due to IAV is counter-intuitive to current initiatives to reduce bacterial antibiotic resistance.
Strict biosecurity, proper pig flow in a production system, and preventing transmission of human IAV to pigs through personal protective equipment are important control measures for IAV on swine farms. However, vaccinations for IAV-S are the most common and necessary methods to control swine influenza. Current inactivated virus vaccines fail to cross-protect against the massive number of antigenically diverse strains circulating in swine and against the threat of human spillover IAV that had significantly impacted the diverse IAV ecology since 1998 when the first H3N2 human transmission occurred that profoundly affected the industry. As traditional vaccines fail, the industry must explore novel immunogens/antigens and vaccination strategies that will demonstrate broad, cross-protective immune responses in the pig.
Our team recently developed a HA stem-based immunogen designated “HIV6HB-HASTEM” based on the hemagglutinin (HA) of a human H3 virus (A/Hong Kong/8/68), which had shown its binding with the monoclonal antibody specific for the most conserved epitope (CR9114) among influenza A and B viruses to date. More importantly, mice immunized with this antigen (10 µg, three times) developed a high level of ELISA antibody against the immunogen and were protected from a lethal challenge of H1 and H3 IAV strains. As a proof-of-concept for the universal vaccine platform, we conducted a pig study using a random block design to assess if the immunogenicity of HIV6HB-HASTEM for swine and the degree of cross-reactivity of the antibodies with various H1 and H3 strains of IAV-S. Pigs were immunized three times with two different doses of the immunogen via two different routes. Two different adjuvants were used with the immunogen. All vaccinated pigs developed antibodies against the immunogen regardless of doses and routes, although IM injection and an oil-emulsion adjuvant induced a higher level of the antibodies, indicating the immunogenicity of the immungen for swine. However, neither virus-neutralizing antibodies nor HI antibodies were detected in these pigs, implying that this particular immunogen may elicit protective immunity in swine in a way different from what traditional IAV-S vaccines induce. Nonetheless, it remains to further investigate if the immune response induced by this immunogen can provide pigs clinical protection against IAV-S challenge.