title: Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs.
abstract: HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming-intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Roheila
authors.initials: R
authors.lastname: Seyedtabaei
authors.affiliation: Department of Bioengineering, Henan University of Technology, Zhengzhou 450052, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Henan University of Technology, Zhengzhou 450052, China.
authors.forename: Laiting
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D005260:Female; D006017:Glycolipids / Q000737:chemistry*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006168:Guinea Pigs; D006678:HIV / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D057134:Antibodies, Neutralizing; D006017:Glycolipids; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D058425:Vaccines, Virus-Like Particle; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor