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Table 2 Evaluation of vectored delivery of bNAbs against HIV-1 in animal models

From: Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1

Experimental design Model Delivery Antibody Highest rAAV genome copies given Challenge virus Challenge route Week of 1st challenge post vectored delivery [Antibody] in serum at challenge Viremia in experimental arm Viremia in control arm References
Expression Rag1 KO mice rAAV2 b12 5 × 1011 HIV-1 IIIB N/A (in vitro neutralization with serum) 20 2–6 μg/ml 1/6 not neutralize No control [67]
Protection Macaques rAAV1 4L6, 5L7, or N4 immunoadhesins 2 × 1013 SIVmac316 Intravenous 4 0–190 μg/ml (1/9 developed ADA) 3/9 after 1 challenge 6/6 after 1 challenge [68]
Protection HuPMBC-NSG mice rAAV8 b12 or VRC01 1 × 1011 HIV NL4-3 Intravenous 4 198–313 μg/ml 0/8 after 1 challenge 8/8 after 1 challenge [73]
Protection BLT mice rAAV8 VRC01 1 × 1011 HIV JR-CSF Intravaginal 4 45–151 μg/ml 2/10 after 15 challenges 9/9, after mean 4.25 challenges [77]
Protection BLT mice rAAV8 VRC07-G54W 1 × 1011 HIV REJO.c Intravaginal 4 56–118 μg/ml 0/13 after 21 challenges 12/12, after mean 7.45 challenges [77]
Maintenance Hu-CD34-NSG mice rAAV2 10-1074 2.5 × 1011 HIV YU-2-NL4-3 N/A N/A ~ 200 μg/ml 1/7 rebounded No control [80]
Protection Macaques rAAV1 IgG1 versions of 4L6 or 5L7 1.6 × 1013 SIVmac239 Intravenous 14 or 44 0–270 μg/ml (9/12 developed ADA) 11/12 after 6 challenges 6/6 after 6 challenges [106]
Protection Macaques, with cyclosporine administration (CsA) for 4 weeks rAAV8 Simianized VRC07 1 × 1013 SHIV-BaLP4 Intrarectal 5.5 0–39 μg/ml (1/6 developed ADA during CsA, 2/5 after CsA) 2/6 after 1 challenge 5/5 after 1 challenge [107]
Protection Macaques rAAV1/2 Rhesus eCD4-Ig with rhesus tyrosine-protein sulfotransferase 2 2.5 × 1013 SHIV-AD8 Intravenous 8 17–77 μg/ml 0/4 after 6 challenges 4/4 after 6 challenges [108]