title: Interaction between hexon and L4-100K determines virus rescue and growth of hexon-chimeric recombinant Ad5 vectors.
abstract: The immunogenicity of recombinant adenovirus serotype 5 (rAd5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against hexon hypervariable regions (HVRs). Preexisting immunity can be circumvented by replacing HVRs of rAd5 hexon with those derived from alternate adenovirus serotypes. However, chimeric modification of rAd5 hexon HVRs tends to cause low packaging efficiency or low proliferation of rAd5 vectors, but the related mechanism remains unclear. In this study, several Ad5-based vectors with precise replacement of HVRs with those derived from Ad37 and Ad43 were generated. We first observed that a HVR-exchanged rAd5 vector displayed a higher efficacy of the recombinant virus rescue and growth improvement compared with the rAd5 vector, although most hexon-chimeric rAd5 vectors constructed by us and other groups have proven to be nonviable or growth defective. We therefore evaluated the structural stability of the chimeric hexons and their interactions with the L4-100K chaperone. We showed that the viability of hexon-chimeric Ad5 vectors was not attributed to the structural stability of the chimeric hexon, but rather to the hexon maturation which was assisted by L4-100K. Our results suggested that the intricate interaction between hexon and L4-100K would determine the virus rescue and proliferation efficiency of hexon-chimeric rAd5 vectors.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yan
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Dong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Baoming
authors.initials: B
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Lizheng
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
mesh_terms: D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000737:chemistry*; D000914:Antibodies, Viral / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C018315:hexon capsid protein, Adenovirus