Table 2.

Protection against SHIV mucosal challenge following intravenous parenteral administration of HIV-MAbs

Reference	MAbs	MAb Dosage	SHIV Challenge	Protection	Notes
Mascola [30]	2G12 2G12 + 2F5	15 mg/kg 15 mg/kg @	Vaginal, sHDa SHIV89.bPD ″	2/4 2/5	First demonstration of modest protection against mucosal SHIV challenge w/mAbs.
Parren [34]	b12 ″ ″	1 mg/kg 5 mg/kg 25 mg/kg	Vaginal, sHD SHIV162.P4 ″ ″	0/4 2/4 4/4	MAb protection was dose-dependent.
Hessell [24]	b12 b12KA b12LALA	25mg/kg ″ ″	Vaginal, sHD SHIVSF162P3	8/9 8/9 5/9	Decreased protection without Fc function.
Hessell [25]	b12 b12LALA	1 mg/kg (weekly) ″	Vaginal, rLD SHIV162.P4 ″	20X RRb 10X RR	First repeated low dose SHIV challenge study: less mAb required for protection. Fc important.
Hessell [26]	2G12	40 mg/kg	Vaginal, sHD, SHIVSF16273	3/5	Half-life of 2G12 in serum: 7.7-12.2 days. Half-life in vaginal secretions: <24 hrs.
Hessell [27]	2F5 4E10	50 mg/kg 50 mg/kg	Rectal, sHD SHIVBa-L ″	5/6 5/6	MPER mAbs are also protective.
Burton [18]	b12 b6	25 mg/kg 25 mg/kg	Vaginal, sHD SHIVSF162P2 ″	3/4 0/4	Strong neutralizing mAb (b12) more protective than weakly neutralizing mAb (b6).
Moldt [32]	PGT121 ″ ″	0.2 mg/kg 1 mg/kg 5 mg/kg	Vaginal, sHD, SHIVSF162P3 ″ ″	3/5 5/5 5/5	Potently neutralizing mAb (PGT121) achieved protection at low dose
Moldt [33]	b12 NFb12	1 mg/kg (weekly)	Vaginal, rLDc, SHIVSF162 ″	4.5X RR 3.0X RR	Nonfucosylated b12 (higher affinity for Fcγ RIIIa and ↑ADCC) did not show enhanced protection.
Klein [28]	2F5 ″ ″ 2F5 (Fab)	5 mg/kg 25 mg/kg 50 mg/kg 25 mg/kg	Vaginal, sHD SHIVBaL ″ ″ ″	3/5 5/5 5/5 0/4	Serum and vaginal PK and PD: serum mAb levels were higher and more predictive of protection than vaginal mAbs. Fab mAb not protective.
Ko [29]	VRC01 VRC01-LS	0.3 mg/kg ″	Rectal, sHD SHIVBaLP45 ″	2/12 7/12	VRC01-LS, engineered for enhanced FcRn binding, had 3X longer serum half-life and was more protective than VRC01.
Pegu [35]	VRC01 ″ ″ 10E8 ″ ″ PG9 ″ ″	0.3 mg/kg 5 mg/kg 20 mg/kg 0.3 mg/kg 5 mg/kg 20 mg/kg 0.3 mg/kg 5 mg/kg 20 mg/kg	Rectal, sHD SHIVBaLP4 ″ ″ Rectal, sHD SHIVBaLP4 ″ ″ Rectal, sHD SHIVBaLP4 ″ ″	4/10 6/6 6/6 3/6 6/6 6/6 0/6 3/6 4/6	Various bNAbs directed against different epitopes on HIV Env were protective.
Rudicell [36]	VRC01 ″ VRC07-523	0.05 mg/kg 0.2 mg/kg 0.3 mg/kg	Rectal, sHD SHIVBaLP4 ″ ″	0/4 3/4 5/12	VRC07-523, a clonal relative of VRC01, engineered to have increased neutralization potency, was more protective than VRC01. EC50: 0.47 μg/ml vs. 2.5 μg/ml.
Shingai [37]	VRC01 ″ ″ PGT 121 ″ ″ 10-1074 ″ ″	20 mg/kg 30 mg/kg 50 mg/kg 1 mg/kg 5 mg/kg 20 mg/kg 1 mg/kg 5 mg/kg 20 mg/kg	Rectal, sHD SHIVDH12-V3AD8 or SHIV AD8E0 ″ ″	0/2 1/2 1/2 3/4 1/2 6/6 1/4 4/4 4/4	Plasma protective neutralization titer (50% animals) ~ 1:100. [3BNC117 and 45-46m2 mAbs showed little to no protection in same concentration range.]
Gautam [23]	VRC01 VRC01-LS 3BNC 117 10-1074	20 mg/kg ″ ″ ″	Rectal, rLD SHIVAD8-EO ″ ″ ″	RR=2.6 RR=4.8 RR=4.3 RR=4.2	A single mAb injection provided protection against several weeks of low dose SHIV rectal challenge (n=6/group).
Moldt [31]	PGT126 ″ ″ PGT126 ″ ″	0.4 mg/kg 2 mg/kg 10 mg/kg 0.4 mg/kg 2 mg/kg 10 mg/kg	Vaginal, sHD SHIVSF163P3 ″ ″ Rectal, sHD SHIVSF163P3 ″ ″	1/5 2/5 5/5 0/4 2/4 3/4	bNAbs protect against both vaginal and rectal challenge routes.
Astronomo [17]	CH54 IgG CH38 mIgA2	50 mg/kg ″	Rectal, sHD SHIVBaLP4	0/8 1/6	These non-neutralizing mAbs were not protective against rectal SHIV challenge.

^asHD: Single high dose SHIV challenge;

^bRR: Relative risk, Cox Proportional Hazard Model;

^crLD: Repeated low dose SHIV challenge