SMNP adjuvant strongly reduces inducible HIV-1 reservoir ex vivo, surpassing MPLA in TLR4-dependent immune activation.

Despite effective antiretroviral therapy (ART), HIV-1 persists in latent cellular reservoirs, posing a significant barrier to a functional cure. These latent reservoirs can reactivate upon cessation of ART, leading to viral rebound. Current strategies often fail to sufficiently target these hidden viral sanctuaries. Adjuvants like Monophosphoryl lipid A (MPLA) and saponin-MPLA nanoparticle (SMNP) are potent immunostimulants known to boost vaccine efficacy by enhancing immune responses. Investigating their direct effects on HIV-1 latency in ART-treated individuals is crucial, as chronic immune activation in PWH might alter their impact on viral reservoirs.

Researchers investigated the effects of MPLA and SMNP on immune activation and HIV-1 latency. They stimulated monocyte-derived dendritic cells (DCs) with these adjuvants and measured TLR4-dependent cytokine production and costimulatory receptor expression. The ability of cytokines from stimulated DCs to induce HIV-1 transcription was assessed using a J-Lat cell model. Crucially, they also treated PBMC (peripheral blood mononuclear cells) from people with HIV-1 (PWH) and healthy donors ex vivo with MPLA and SMNP to evaluate cytokine responses and the impact on the inducible HIV-1 reservoir size.

Both MPLA and SMNP effectively triggered TLR4-dependent cytokine production in monocyte-derived dendritic cells (DCs), with SMNP eliciting a stronger response based on costimulatory receptor expression and cytokine profiles. Cytokines produced by these adjuvant-stimulated DCs were capable of inducing HIV-1 transcription in a J-Lat cell model, indicating their potential to reactivate latent virus. Notably, SMNP, but not MPLA, induced a cytokine response in PBMC from PWH, although this response was lower compared to healthy donor PBMC.