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A reassortment-incompetent live attenuated influenza virus vaccine for use in protection against pandemic virus strains

Hai, Rong, Garcia-Sastre, Adolfo, Swayne, David E., Palese, Peter
Journal of Virology 2011 v.85 no.14 pp. 6832
Influenza A virus, Influenza B virus, RNA, antibodies, cell-mediated immunity, genetic recombination, hemagglutinins, immune response, inactivated vaccines, influenza, live vaccines, mice, models, pandemic, recombinant vaccines, vaccination, vaccine development, viruses
Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns over their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity over inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live vaccine strain, we have designed a chimeric virus that takes advantage of the fact that influenza B and A viruses do not reassort. Our novel vaccine model makes use of an attenuated influenza B virus that we have manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3) and VN (H5) vaccine strains. All recombinant viruses were attenuated both in vitro and in vivo, and immunization with these recombinant viruses protected mice against lethal influenza A virus infection. Overall, our data indicate that the chimeric live attenuated influenza B viruses expressing the modified influenza A hemagglutinin are effective LAIVs.