MASIC A, Pyo HM, Babiuk S, Zhou Y, et al. An eight-segment swine influenza virus harbouring H1 and H3 hemagglutinins is attenuated and protective against H1N1 and H3N2 subtypes in pigs. J Virol. 2013 Jul 10.
Swine influenza virus (SIV) infections continue to cause production losses in the agricultural industry in addition to being a human public health concern. The primary method to control SIV is through vaccination. Currently used killed SIV vaccines must be closely matched to the challenge virus and their protection efficiency is limited. Live attenuated influenza vaccines (LAIV) provide strong, long-lived, cell mediated and humoral immunity against different influenza subtypes without need for antigen matching. Here we report a generation of new potential LAIV, an eight segment SIV harbouring two different SIV hemagglutinins (H1 and H3) in genetic background of H1N1 SIV. This mutant SIV was generated by fusing the H3 HA ectodomain from A/Swine/Texas/4199-2/98 (H3N2) to the cytoplasmic tail, transmembrane domain and stalk region of NA from A/Sw/Saskatchewan/18789/02 (H1N1) SIV. While in vitro this H1H3 chimeric SIV showed similar kinetics and growth properties to parental wild type virus when was propagated in the presence of exogenous neuraminidase. In vivo the H1H3 chimeric SIV was highly attenuated in pigs, demonstrating the great potential to serve as dual LAIV. Furthermore, vaccination with H1H3 virus elicited robust immune responses which conferred complete protections to both H1 and H3 SIV subtypes infection in pigs.
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