title: Unpolarized release of vaccinia virus and HIV antigen by colchicine treatment enhances intranasal HIV antigen expression and mucosal humoral responses.
abstract: The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.
authors.affiliation: Mucosal Immunity Research Group, the State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Bao
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhou
authors.forename: Benxia
authors.initials: B
authors.lastname: He
authors.forename: Maohua
authors.initials: M
authors.lastname: Zhong
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018938:Caco-2 Cells; D002522:Chlorocebus aethiops; D003078:Colchicine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D014616:Vaccinia virus / Q000276:immunology*; D014709:Vero Cells
chemical_list: D015488:HIV Antigens; D003078:Colchicine