PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo.

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Myeloid dendritic cells (mDCs) play a dual role in HIV pathogenesis and antiviral immunity.
• Polyinosinic polycytidylic acid (polyIC, PIC) stimulates DCs and enhances anti-HIV responses.
• Stabilized polyICLC (PICLC) is a potential vaccine adjuvant, necessitating understanding of its impact on HIV infection.

Purpose of the Study:

• To investigate how PICLC influences HIV infection in monocyte-derived DCs (moDCs) and DC-T cell mixtures.
• To evaluate the effect of PICLC on SIV transmission and replication in vivo in macaques.

Main Methods:

• In vitro studies using moDCs and DC-T cell mixtures exposed to PICLC and other dsRNAs.
• In vivo macaque rectal transmission studies with PICLC administration before or during SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge.

Main Results:

• PICLC activated DCs and T cells, upregulated immune markers (α4β7, CD169), and induced type I IFN responses in vitro.
• In vitro, dsRNA type and timing differentially affected HIV infection.
• Rectal PICLC treatment induced local and systemic immune activation without enhancing SIV transmission; acquisition was marginally reduced in a high-dose challenge model.
• SIVΔNef viremia was higher in PICLC-treated animals, correlating with DC and T cell activation.

Conclusions:

• PICLC activates immune cells and influences HIV infection dynamics in vitro.
• PICLC administration did not increase SIV transmission in macaques and showed a marginal reduction in acquisition.
• PICLC holds potential as part of an anti-HIV strategy to limit infection and enhance immunity.