title: Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.
abstract: We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA) non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009) H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+) T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1) than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1) in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+) T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses to macaques against pandemic influenza virus infection than did the split vaccine.
authors.affiliation: Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Arikata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shingo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Misako
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ishigaki
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishida
authors.forename: Kosuke
authors.initials: K
authors.lastname: Soda
authors.forename: Van Loi
authors.initials: VL
authors.lastname: Pham
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Torii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohkubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D002853:Chromatography, Liquid; D016207:Cytokines / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005805:Genes, MHC Class I / Q000235:genetics* / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D014162:Transfection
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D007252:Influenza Vaccines