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In 2012, swine influenza surveillance detected a novel reassorted influenza A virus (IAV) strain containing human-seasonal hemagglutinin (HA) and neuraminidase (NA). Subsequently, these viruses reassorted, maintaining only the human-origin H3, which resulted in a new lineage of viruses that became the most frequently detected H3 clade in US swine (2010.1 HA clade). Here, we assessed the antigenic phenotype, virulence, and transmission characteristics of this virus lineage following its introduction to swine. Relative to 2010.1 viruses from 2012 and 2014, recent 2010.1 contemporary strains from 2015 to 2017 resulted in equivalent macroscopic lung lesions and transmission in pigs. A single mutation at amino acid residue 145 within the previously defined HA antigenic motif was associated with a change of antigenic phenotype, potentially impairing vaccine efficacy. Contemporary 2010.1 viruses circulating in swine since 2012 were significantly different from both pre-2012H3N2 in swine and human-seasonal H3N2 viruses and demonstrated continued evolution within the lineage. • Human-like H3N2 swine 2010.1 viruses evolved antigenically at position 145 in the HA. • Recent 2010.1 viruses with different genome combinations were not more virulent or transmissible compared to the prototype. [ABSTRACT FROM AUTHOR]

Live-attenuated influenza virus (LAIV) prime-boost vaccination previously conferred protection against heterologous H3N2 swine influenza challenge, including in piglets with maternally derived antibodies (MDA). Conversely, a whole-inactivated virus (WIV) vaccine was associated with enhanced disease. This study was aimed at identifying immune correlates of cross-protection. Piglets with and without MDA received intramuscular adjuvanted WIV or intranasal LAIV, and were challenged with heterologous H3N2. WIV induced cross-reactive IgG, inhibited by MDA, and a moderate T cell response. LAIV elicited mucosal antibodies and T cells cross-reactive to the heterologous challenge strain. The presence of MDA at LAIV vaccination blocked lung and nasal antibody production, but did not interfere with T cell priming. Even without mucosal antibodies, MDA-positive LAIV vaccinates were protected, indicating a likely role for T cells. Based on the data, one LAIV dose can induce cell-mediated immunity against antigenically divergent H3N2 influenza virus despite passive antibody interference with humoral immune responses. [ABSTRACT FROM AUTHOR]