HIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates

PLoS One. 2018 Nov 30;13(11):e0207794. doi: 10.1371/journal.pone.0207794. eCollection 2018.


HIV-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. HIV-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. A therapeutic vaccine boosting cellular immunity against HIV-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for long-term drug therapies. An approach to elicit strong T cell-based immunity is to direct virus protein antigens specifically to dendritic cells (DCs), which are the key cell type for controlling immune responses. For eliciting therapeutic cellular immunity in HIV-1-infected individuals, we developed vaccines comprised of five T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol (HIV5pep) fused to monoclonal antibodies that bind either, the antigen presenting cell activating receptor CD40, or the endocytic dendritic cell immunoreceptor DCIR. The study aimed to demonstrate vaccine safety, establish efficacy for broad T cell responses in both primed and naïve settings, and identify one candidate vaccine for human therapeutic development. The vaccines were administered to Rhesus macaques by intradermal injection with poly-ICLC adjuvant. The animals were either i) naïve or, ii) previously primed with modified vaccinia Ankara vector (MVA) encoding HIV-1 Gag, Pol, and Nef (MVA GagPolNef). In the MVA-primed groups, both DC-targeting vaccinations boosted HIV5pep-specific blood CD4+ T cells producing multiple cytokines, but did not affect the MVA-elicited CD8+ T cell responses. In the naive groups, both DC-targeting vaccines elicited antigen-specific polyfunctional CD4+ and CD8+ T cell responses to multiple epitopes and these responses were unchanged by a subsequent MVA GagPolNef boost. In both settings, the T cell responses elicited via the CD40-targeting vaccine were more robust and were detectable in all the animals, favoring further development of the CD40-targeting vaccine for therapeutic vaccination of HIV-1-infected individuals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • CD40 Antigens / immunology*
  • Dendritic Cells / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • HIV Antibodies / immunology*
  • HIV-1 / immunology*
  • Macaca mulatta
  • Male
  • Molecular Targeted Therapy
  • Receptors, Immunologic / immunology*


  • AIDS Vaccines
  • CD40 Antigens
  • Epitopes, T-Lymphocyte
  • HIV Antibodies
  • Receptors, Immunologic

Grant support

The study was funded within the Vaccine Research Institute (ANRS/INSERM) HIV vaccine program and was supported by the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77. Advanced Bioscience Laboratories, Inc., provided contract services for the non-human primate study and some of the listed authors are employees of this commercial company. Oncovir, Inc., is a commercial company that provided Hiltonol for this study at no cost. The funder provided support in the form of salaries for all authors with Vaccine Research Institute affiliation authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Authors employed by ABL helped design and manage the study, including animal care and ELISPOT assay. Dr. Salazar, who is employed by Oncovir, Inc., on advised aspects related to use and formulation of Hiltonol.