title: Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein.
abstract: Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza.
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Andrey
authors.identifier: 0000-0003-2156-1635
authors.initials: A
authors.lastname: Rekstin
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Isakova-Sivak
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Petukhova
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Daniil
authors.initials: D
authors.lastname: Korenkov
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Losev
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Smolonogina
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Tretiak
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Donina
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Shcherbik
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bousse
authors.affiliation: Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Rudenko
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009698:Nucleoproteins; D014613:Vaccines, Attenuated; D009439:Neuraminidase