A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice

PLoS One. 2014 Sep 12;9(9):e106597. doi: 10.1371/journal.pone.0106597. eCollection 2014.


Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV) displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G). The clade B Env immunogen is an Env-VSV G hybrid (EnvG) in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5'terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs), and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN) or intramuscular (IM) administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10(4)-10(5), with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Female
  • Genetic Vectors / metabolism*
  • HIV-1 / metabolism*
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Immunization
  • Lung / immunology
  • Lymphocyte Count
  • Mice, Inbred BALB C
  • Protein Conformation
  • Protein Multimerization
  • Spleen / immunology
  • Vaccines, Attenuated / immunology*
  • Vesicular stomatitis Indiana virus / metabolism*
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / immunology*
  • env Gene Products, Human Immunodeficiency Virus / metabolism


  • Vaccines, Attenuated
  • env Gene Products, Human Immunodeficiency Virus