Incorporation of Ebola glycoprotein into HIV particles facilitates dendritic cell and macrophage targeting and enhances HIV-specific immune responses

• Published in: PloS one Vol. 14; no. 5; p. e0216949
• Main Authors: Ao, Zhujun, Wang, Lijun, Mendoza, Emelissa J, Cheng, Keding, Zhu, Wenjun, Cohen, Eric A, Fowke, Keith, Qiu, Xiangguo, Kobinger, Gary, Yao, Xiaojian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.05.2019; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; AIDS Vaccines - administration & dosage; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Analysis; Animals; Antigens; Biology and Life Sciences; Chemokine CCL3 - genetics; Chemokine CCL3 - immunology; Cytokines; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - virology; Dendritic structure; Ebola virus; Ebolavirus; Ebolavirus - chemistry; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Female; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; Gag protein; Gene Expression; Glycoproteins; Health aspects; Health sciences; HEK293 Cells; HIV; HIV Antibodies - biosynthesis; HIV infections; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - growth & development; HIV-1 - immunology; Human immunodeficiency virus; Human performance; Humans; Humoral immunity; Immune response; Immune response (humoral); Immune system; Immunity; Immunity, Cellular - drug effects; Immunity, Humoral - drug effects; Immunization; Immunogenicity; Immunogenicity, Vaccine; Immunology; Immunotherapy; Infection; Infections; Infectious diseases; Inflammation; Interleukin 4; Interleukin-4 - genetics; Interleukin-4 - immunology; Laboratories; Lymphocytes; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - immunology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - virology; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Molecular Targeted Therapy; Monocytes; Mucin; Peptides; Primary Cell Culture; Product development; Proteins; Public health; Replication; Research and Analysis Methods; Spleen - cytology; Spleen - drug effects; Spleen - immunology; Splenocytes; Vaccines; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Virology; Virus-like particles; Viruses; Zoonoses; Canada; Montreal Quebec Canada; Manitoba Canada; Thailand; Quebec Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216949

The development of an effective vaccine against HIV infection remains a global priority. Dendritic cell (DC)-based HIV immunotherapeutic vaccine is a promising approach which aims at optimizing the HIV-specific immune response using primed DCs to promote and enhance both the cellular and humoral arms of immunity. Since the Ebola virus envelope glycoprotein (EboGP) has strong DC-targeting ability, we investigated whether EboGP is able to direct HIV particles towards DCs efficiently and promote potent HIV-specific immune responses. Our results indicate that the incorporation of EboGP into non-replicating virus-like particles (VLPs) enhances their ability to target human monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). Also, a mucin-like domain deleted EboGP (EboGPΔM) can further enhanced the MDDCs and MDMs-targeting ability. Furthermore, we investigated the effect of EboGP on HIV immunogenicity in mice, and the results revealed a significantly stronger HIV-specific humoral immune response when immunized with EboGP-pseudotyped HIV VLPs compared with those immunized with HIV VLPs. Splenocytes harvested from mice immunized with EboGP-pseudotyped HIV VLPs secreted increased levels of macrophage inflammatory proteins-1α (MIP-1α) and IL-4 upon stimulation with HIV Env and/or Gag peptides compared with those harvested from mice immunized with HIV VLPs. Collectively, this study provides evidence for the first time that the incorporation of EboGP in HIV VLPs can facilitate DC and macrophage targeting and induce more potent immune responses against HIV.