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

Lin, Allen; Balazs, Alejandro B.

doi:10.1186/s12977-018-0449-7

Retrovirology

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]

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ISSN: 1742-4690

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