Fig. 6: Therapeutic efficacy of Nb457s in HIV-1-infected NDG-HuPBL mice.
a Experimental timeline outlining the immunotherapeutic intervention using Nb457 and Ibalizumab in HIV-1CH058–challenged humanized mice. Intraperitoneal (i.p.) injections were administered at 1 day post-infection (dpi), followed by subcutaneous (s.c.) administrations at 3 dpi, 5 dpi, and 7 dpi after HIV-1CH058 challenge. Each treatment group received four administrations, including Nb457-Fc, Nb457-NbHSA-Nb457, Ibalizumab, and a negative control Nb (Nb Ctl, SNB02, one of our published nanobodies specific for envelope protein of SFTSV). The dosage of Nbs or antibodies was 400 μg (~20 mg/kg). The initial HIV-1 inoculum was 10 ng P24. Mice were monitored for four weeks post HIV-1 challenge. A summary of the treatment groups (n = 4 mice, female) with distinct interventions is presented in the lower table. b Quantification of plasma viral loads in five groups of NDG-HuPBL mice, color-coded and labeled as in the table in (a), assessed through qRT-PCR. Nb457-Fc (green line), Nb457-NbHSA-Nb457 (cyan line), Ibalizumab (orange line), and Nb Ctl (pink line), No HIV-1 (gray line). Each line represents average data from one group of mice (n = 4 in each group). Data from an individual mouse in the Nb457-NbHSA-Nb457 group is represented by a cyan dashed line. Data are presented as SEM. c Viral outgrowth assay (VOA) results of splenocytes from the aforementioned HIV-1-infected NDG-HuPBL mice (n = 4 in each group), indicating viral load in copies per milliliter culture supernatant. Data are presented as mean ± SEM. Two-sided Mann–Whitney test was applied to compare the treatment group with the Nb control group. Significance levels: ns, not significant; *p < 0.05, **p < 0.01, ***p < 0.001. d Immunofluorescence staining of spleen sections using antibodies specific to HIV-1 nucleocapsid protein (P24) in green, and DAPI (4’,6-diamidino-2-phenylindole) for nuclei in blue. Representative spleen sections were visualized under ×10 or ×60 objective, with indicated scale bars (200 μm or 50 μm), respectively. Source data are provided as a Source Data file.
