title: Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques.
abstract: Human immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 10(8) PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thippeshappa
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: Baoping
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Cleveland
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Washington National Primate Research Center, University of Washington, Seattle, Washington, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Polacino
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA Washington National Primate Research Center, University of Washington, Seattle, Washington, USA Hus@wanprc.org.
authors.forename: Shiu-Lok
authors.identifier: http://orcid.org/0000-0003-4336-7964
authors.initials: SL
authors.lastname: Hu
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; C514793:gp120 protein, Human immunodeficiency virus 1; C514797:gp160 protein, Human immunodeficiency virus 1