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

Author
item HAI, RONG - Mount Sinai Hospital
item GARCIA-SASTRE, ADOLFO - Mount Sinai Hospital
item Swayne, David
item PALESE, PETER - Mount Sinai Hospital

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2011
Publication Date: 7/14/2011
Citation: Hai, R., Garcia-Sastre, A., Swayne, D.E., Palese, P. 2011. A reassortment-incompetent live attenuated influenza virus vaccine for use in protection against pandemic virus strains. Journal of Virology. 85(14):6832-6843.

Interpretive Summary: Live influenza vaccines (LAIV) are safe for use in protection against seasonal H1 and H3 influenza strains in humans. However, there is a concern these vaccines could swap genes with a field influenza virus, creating a virus with a greater ability to cause disease. In this study, a hybrid virus was created which had genes from influenza A and B type viruses. This virus will not swap genes with either influenza A or B viruses. In a mouse challenge model, all hybrid viruses were safe and when used to immunize mice, the mice were protected from lethal influenza A virus infections. The hybrid virus did not infect chickens in experimental studies. This hybrid virus has the potential to be a human influenza vaccine virus.

Technical Abstract: 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 may be effective LAIVs.