Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

Conclusions: These finding suggest that Poly-ICLC could be safely used for inducing transient innate immune responses in treated HIV+ subjects indicating promise as an adjuvant for HIV therapeutic vaccines. Trial Registration: www.ClinicalTrials.gov, identifier: NCT02071095. Introduction Innate immune dysregulation during HIV infection hinders the formation of anti-HIV adaptive immunity (1–6) resulting in rampant viral dissemination and progression to AIDS. Adherence to combination anti-retroviral therapy (cART) regimens controls viremia, restores CD4+T cell counts and reverses immune dysfunction to a larg extent. However, cART fails to eradicate latent viral reservoirs, posing a major barrier to achieving sterilizing cure (7). Thus, safe and effective adjuvants that stimulate innate immune responses (8) and reactivate latent HIV, allowing for killing of infected cells, are likely to be a vital element of successful therapeutic immunization strategies in aviremic patients (9). Pattern recognition receptors, such as Toll-like receptors (TLRs), are key activators of innate immunity. These germ line encoded receptors induce rapid inflammation in response to a wide range pathogen associated molecular patterns (PAMPs) (10). Of the 10 TLRs expressed in humans, TLRs 1,2,4,5,6, and 10 are expressed on the cell surface and recognize pathogenic cell membrane components such as lipoproteins, peptidoglycans, flagellin, etc. TLR 3, TLR 7/8, and TLR9 are intracellul...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research