title: Enhanced mucosal immune responses to HIV virus-like particles containing a membrane-anchored adjuvant.
abstract: Previously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.
authors.affiliation: Zetra Biologicals LLC, Tucker, Georgia, USA.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Vassilieva
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Vzorov
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Wang
authors.forename: Jadranka
authors.initials: J
authors.lastname: Bozja
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D005408:Flagellin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006168:Guinea Pigs; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; D005408:Flagellin