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Background One of the NIH high-priority HIV/AIDS research objectives is to discover novel therapeutics aimed at developing safe, tolerable, strategies that targets cellular protein to induce long-term antiviral suppression. This current research aims at designing a novel targeted nano-formulation combining cell targeting and antiretroviral therapy to provide double protection against HIV-1. Methods CCR5 targeted combination antiretroviral drugs (cARV) loaded nanoparticles (NPs) were synthesized based on water-in-oil-in-water (W-O-W) emulsion methodology. For targeting CCR5+ T cells, a modified high affinity CCR5 monoclonal Ab (XFCCR5 mAb), was isolated from XF-CCR5 hybridoma cells. The XFCCR5 mAbs were covalently conjugated through their C-terminus by replacing the NHS group on FTC+DTG NPs with covalent amide bond. The CCR5 mAb binding was evaluated by SDS–PAGE methods. The CCR5-specific binding affinity of XFCCR5-FTC+DTG NP in compared with XFCCR5 monoclonal antibody (mAb) was evaluated by flow cytometry using CD4+CCR5+ TZM-bl cell line and PBMCs. The intracellular pharmacokinetic (PK) profile in TZMbl cells was evaluated by LC-MS/MS analysis, whereas in vitro efficacy was evaluated based on Steady-Glo® Luciferase Assay System using TZM-bl cells. Results XFCCR5-FTC+DTG NPs obtained averaged 173 ± 23 nm (mean ± SEM, n = 3) with 2.2 ± 0.47 mg XFCCR5 mAb bound per mg cARV NP. The formulation % entrapment efficiency of DTG and FTC respectively, to be 55 ± 1.6% and 42.6 ± 5.6%. The specific binding affinity (Km) of XFCCR5-FTC+DTG NP and XFCCR5 mAb were estimated to be 0.0057 and 0.0377, higher compared with wild-type anti-CCR5 mAb with higher Km value 0.303. Finally, the 4-day HIV-infection protection study result illustrates IC50 in case of XFCCR5-FTC+DTG NP and XFCCR5 NP to be as low as 0.0069 and 0.0031 µg/mL, respectively, compared with 1.771 µg/mL for XFCCR5 mAb (Figure 1, TZM-bl and Figure 2, PBMCs). Conclusion This nano-formulation aimed at duel protection by preventing HIV binding to CCR5+CD4+T cell due to CCR5 receptor blocking. These result support protection against HIV and maintenance of cARV drug levels. This novel formulation could be supportive of immune-alternative to achieve functional-cure against HIV. Disclosures All authors: No reported disclosures.

2501. CCR5 Targeted ARV Loaded Nanoparticle: Dual Protection for HIV Functional Cure