Abstract
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.
Highlights
Acquired immunodeficiency syndrome (AIDS) is a slow degenerative disease of the immune and nervous systems resulting from HIV infection
EBOV glycoprotein (EboGP) was detected in HIVgp(M)/EboGP-virus-like particles (VLPs) and EboGP-VLPs (Fig 1B, lanes 1 and 2), while HIV gp120 was detected in HIVgp(M)/EboGP-VLP and HIVgp(M)-VLPs (Fig 1B, lanes 1 and 3)
Since EboGP pseudotyping HIV VLPs significantly enhanced targeting towards monocyte-derived dendritic cells (MDDCs)/ monocyte-derived macrophages (MDMs), we investigated whether the incorporation of EboGP into HIV VLPs could increase the immunogenicity of HIV VLPs in vivo
Summary
Acquired immunodeficiency syndrome (AIDS) is a slow degenerative disease of the immune and nervous systems resulting from HIV infection. The development of efficient protective vaccines to prevent HIV infection has become a major priority. The immunogenicity and protective efficacy of several vaccine strategies against HIV infection have been evaluated in vivo (reviewed in [4]). Among all the vaccines tested in non-human primate (NHP) models with simian immunodeficiency virus (SIV), live attenuated SIVs remain the most efficacious vaccines in protecting against wild-type SIV [5]. A live attenuated HIV vaccine for humans is unfeasible due to considerable safety issues. Much effort has been made to develop other types of vaccines, including inactivated HIV virions and virus-like particles (VLPs) [6,7,8,9]
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