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] |