Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model.
This study sought to improve an existing live attenuated influenza vaccine (LAIV) by including nucleoprotein (NP) from wild-type virus rather than master donor virus (MDV). H7N9 LAIV reassortants with 6:2 (NP from MDV) and 5:3 (NP from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. Although, in general, the 6:2 reassortant induced greater cell-mediated immunity in C57BL6 mice than the 5:3 vaccine, mice immunized with the 5:3 LAIV were better protected against heterologous challenge. The 5:3 LAIV-induced CTLs also had better in vivo killing activity against target cells loaded with the NP366epitope of recent influenza viruses. Modification of the genome of reassortant vaccine viruses by incorporating the NP gene from wild-type viruses represents a simple strategy to improve the immunogenicity and cross-protection of influenza vaccines.
Institute of Experimental Medicine, Saint Petersburg, Russia. Electronic address: isakova.sivak@gmail.com.
Irina
I
Isakova-Sivak
Institute of Experimental Medicine, Saint Petersburg, Russia.
Daniil
D
Korenkov
Institute of Experimental Medicine, Saint Petersburg, Russia.
Tatiana
T
Smolonogina
Institute of Experimental Medicine, Saint Petersburg, Russia.
Tatiana
T
Tretiak
Institute of Experimental Medicine, Saint Petersburg, Russia.
Svetlana
S
Donina
Institute of Experimental Medicine, Saint Petersburg, Russia.
Andrey
A
Rekstin
Institute of Experimental Medicine, Saint Petersburg, Russia.
Anatoly
A
Naykhin
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Svetlana
S
Shcherbik
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Nicholas
N
Pearce
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Li-Mei
LM
Chen
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Tatiana
T
Bousse
Institute of Experimental Medicine, Saint Petersburg, Russia.
Larisa
L
Rudenko
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003080:Cold Temperature; D056738:Cross Protection; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016865:Reassortant Viruses / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014774:Virulence
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D009698:Nucleoproteins; D014613:Vaccines, Attenuated
Cell-mediated immunity; Cross-protection; Immunodominant epitope; Immunogenicity; Live attenuated influenza vaccine; Mouse model; Nucleoprotein