title: H5N1 influenza virus-like particles produced by transient expression in mammalian cells induce humoral and cellular immune responses in mice.
abstract: Vaccination is an effective way to protect from influenza virus infection. Among the new candidates of influenza vaccines, influenza virus-like particles (VLPs) seem to be promising. Here, we generated 2 types of H5N1 influenza VLPs by co-expressing influenza virus Env (envelope protein) and murine leukemia virus (MLV) Gag-Pol. VLPs generated by co-transfection of pHCMV-wtH5 or pHCMV-mtH5 with pSV-Mo-MLVgagpol and pHCMV-N1 were named as wtH5N1 VLPs or mtH5N1 VLPs. The plasmid of pHCMV-wtH5 encoded the wild-type hemagglutinin (HA) (wtH5) from A/swine/Anhui/ca/2004 (H5N1) with a multibasic cleavage site, while pHCMV-mtH5 encoded the modified mutant-type (mtH5) with a monobasic cleavage site. Influenza virus HA VLPs were characterized and equal amounts of them were used to immunize mice subcutaneously, intraperitoneally, or intramuscularly. The levels of HA-specific IgG1, IFN-γ, and neutralization antibodies were significantly induced in mice immunized with wtH5N1 VLPs or mtH5N1 VLPs via all 3 routes, while HA-specific IgG2a was barely detectable. IL-4 secretion was detected in mice subcutaneously immunized with wtH5N1 VLPs or mtH5N1 VLPs, or intramuscularly immunized with mtH5N1 VLPs. Our results indicated that both H5N1 influenza VLPs could induce specific humoral and cellular immune responses in immunized mice. In conclusion, our study provides helpful information for designing new candidate vaccines against H5N1 influenza viruses.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, No. 44, Xiaohongshan, Wuhan 430071, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zheng
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Huanle
authors.initials: H
authors.lastname: Luo
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D056724:Immunity, Humoral / Q000502:physiology*; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D013552:Swine; D014611:Vaccination / Q000379:methods; D014771:Virion / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015847:Interleukin-4