The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses
Lorena Usero,
Lorna Leal,
Carmen Elena Gómez,
Laia Miralles,
Elena Aurrecoechea,
Ignasi Esteban,
Berta Torres,
Alexy Inciarte,
Beatriz Perdiguero,
Mariano Esteban,
Felipe García,
Montserrat Plana
Affiliations
Lorena Usero
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Lorna Leal
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Carmen Elena Gómez
Centro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
Laia Miralles
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Elena Aurrecoechea
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Ignasi Esteban
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Berta Torres
Infectious Diseases Department, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Alexy Inciarte
Infectious Diseases Department, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Beatriz Perdiguero
Centro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
Mariano Esteban
Centro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
Felipe García
Infectious Diseases Department, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
Montserrat Plana
AIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV.