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. 2021 Sep 15;12:734304. doi: 10.3389/fimmu.2021.734304

Table 1.

Protective and therapeutic efficacy of bNAbs in vivo.

Reference Model System bNAb Human or Monkey Ab Dose given (mg/kg) Passive Transfer or AAV Route Challenge Virus Virus Route Dose In vitro IC50 Projected Conc at time of challenge Isotype Effector function Outcome
Moldt et al. (35) rhesus macaques PGT121 Human 5 P.T. I.V. SHIV-SF162P3 intravaginal challenge 300 TCID50 0.005µg/ml High: 95µg/ml IgG1 N.A. Protection at 5 and 1mg/kg and 3/5 protected at 0.2mg/kg, suggesting that protective serum concentrations for PGT121 is <10µg/ml
1 Medium: 15µg/ml
0.2 Low:1/8µg/ml
Shingai et al. (57) rhesus macaques VRC01 Human Against AD8EO: P.T. I.V. SHIV-DH12-V3AD8 rectal challenge   AD8EO: AD8EO: IgG1 N.A. Neutralizing titers were predictive of protection against both viruses; the higher the antibody conentration the more likely a monkey was to be protected
NIH45-46 VRC01: 50, 20 VRC01: 188-711µg/ml
45-46G54W PGT121 and 10-10-74: 20, 5, 1, 0.2 V3:0.09-0.15µg/ml, PGT121: 1.8-267µg/ml
45-46m2 CD4bs: 0.14µg/ml-6.36µg/ml 10-1074: 19-289µg/ml' 3BNC117: 215-105µg/ml
3BNC117 3BNC117: 5, 1   45-46m2: 2-15µg/ml
12A12 45-46m2: 20, 5 DH12-V3AD8 V3: DH12-V3AD8:
1NC9 Against DH12-V3AD8: SHIV-AD8EO VRC01: 306-395µg/ml
8ANC195 VRC01: 30 V3: 0.01-0.16µg/ml PGT121: 1-282µg/ml
10-1074 PGT121, 10-1074 and 3BNC117: 20, 1, 0.2, 0.05 10-1074: 19-290µg/ml 3BNC117: 3-294µg/ml
PGT121 CD4bs: 0.39-86.27µg/ml 45-46m2: 2-4µg/ml
PGT126 45-46m2: 5
Pegu et al. (32) rhesus macaques 2D5 Human 2D5:40 P.T. I.V. SHIV-SF162P3 rectal challenge 300 TCID50   2D5: 352µg/ml IgG1 N.A. Protection with 2D5 (2/4) despite high concentration, VRC01 against SHIV-SF162P3 afforded complete protection, BalP4 challenges: all monkeys at high and medium doses of VRC01 were protected, at low dose (4/10), 10E8 protected all monkeys at high and medium doses, at low dose (3/6), PG9 protected (4/6) at high dose, (3/6) at medium and no moneys at low dose
VRC01 VRC01 high 60µg/ml, medium 22µg/ml, low 1.31µg/ml
1E9 VRC01, 10E8, PG9: 20, 5, 0.3 BALP4 10E8 high 133µg/ml, medium 31µg/ml, low 1.8µg/ml
PG9 PG9 high 32µg/ml, medium 3.7µg/ml, low 0.28µg/ml
Julg et al. (10) rhesus macaques PGDM1400 Human 2 P.T. I.V. SHIV-325c rectal challenge 500 TCID50 PGDM1400=0.037 ~0.1-10µg/ml IgG1 N.A. CAP256.VRC26 protection at high dose (3/3), medium (3/3), low (3/3), PGMD1400 protection at high dose (4/5), medium (5/5/), low (1/3)
CAP256-VRC26.25-LS 0.4 CAP256-VRC26.25=0.003
0.08
Balazs et al. (18) Hu-PBMC mice 2G12 Human N.A. AAV I.V. NL4-3 I.P. and I.V. 1ng p24   b12: 100µg/ml IgG1 N.A. Mice given b12 were completely protected, mice given 2G12, 2F5 and 4E10 were partially protected. Mice expressing varying doses of VRC01 showed partial protection: Mice expressing less than 10µg/ml succumbed to infection but mice expressing >10µg/ml were protected
b12 2G12: 150µg/ml
2F5 2F5: 20µg/ml
4E10 10ng p24 4E10: 20µg/ml
VRC01 VRC01: 0.1-200µg/ml
Balazs et al. (21) BLT humanized mice b12 Human N.A. AAV I.V. REJO.c intravaginal challenge 16ng p24 REJO.c   b12: ~100-300µg/ml IgG1 N.A. bNAbs can maintain long lasting expression using VIP, can also reach high concentrations that are protective against repeated mucosal challenge
VRC01 JR-CSF 50ng p24 JR-CSF VRC01:~100-300µg/ml
VRC07W VRC07W: ~100µg/ml
Moldt et al. (58) rhesus macaques PGT126 Human 10 P.T. I.V. SHIV-SF162P3 intravaginal and rectal unknown 0.3µg/ml 10mg/kg: 100-125µg/ml IgG1 N.A. No difference in protection between either route of challenge, suggesting that there is similar effiacy of bNAb proteection against both primary transmission routes
0.4 2mg/kg:25µg/ml
0.4mg/kg: 4µg/ml
Rudicell et al. (59) rhesus macaques VRC01-LS Human 0.3 P.T. I.V. SHIV-BalP4 rectal challenge 12,800 TCID50 VRC01-LS: 0.028µg/ml VRC01-LS: 2.5µg/ml IgG1 N.A. VRC07-523-LS afforded better protection compared to VRC01-LS, suggesting that a more potent antibody can protect at these lower concentrations
VRC07-523-LS 0.2 VRC07-523-LS: 0.005µg/ml VRC07-523-LS: 0.47µg/ml
0.05
Saunders et al. (11) rhesus macaques VRC01 Simian 5 P.T. I.V. SHIV-BalP4 rectal challenge unknown 0.019µg/ml VRC01: 0.1-1µg/ml IgG1 N.A. Introducing an LS mutation into the antibody led to elevated antibody levels for a longer period of time and protected against mucosal challenge for up to two months after last antibody administration
VRC01-LS VRC01-LS: 2-6µg/ml
Ko et al. (59) rhesus macaques VRC01, VRC01-LS Human 0.3 P.T. I.V. SHIV-BalP4 rectal challenge unknown unknown ~20-100µg/ml IgG1 FcRn and FcγRIIIa binding, ADCC VRC01-LS affords better protection against viral challenge than VRC01, due to its enhanced binding with FcRn. No detectable difference in the ability to bind FcRIIIa, suggesting that ADCC is intact
VRC01-LS
Hessell et al. (13) rhesus macaques b12-WT Human 1 P.T. I.V. SHIV-SF162P3 intravaginal challenge TCID50 10 0.18µg/ml b12: ~45-70µg/ml IgG1 b12-WT can mediate effector functions, LALA variant cannot mediate any function Two-fold difference in hazard ratio between WT and LALA variant number of challenges to infection, effector function appears to play a role in this difference in protection
b12-LALA b12-LALA: ~5-55µg/ml,
Hessell et al. (38) rhesus macaques b12-WT Human 25 P.T. I.V. SHIV-SF162P3 intravaginal challenge 300 TCID50 unknown b12-WT: 562µg/ml IgG1 C1q and FcγR binding No difference in protection between b12-WT and b12-KA (8/9 protected), but monkeys given b12-LALA were less protected (5/9)
b12-LALA b12-KA: 616µg/ml
b12-KA b12-LALA: 534µg/ml
Bournazos et al. (37) Luciferase reporter mice transduced with AdV hCCR5-A2-hCD4 3BNC117 mouse-human chimeric (human bNAbs with mouse constant region heavy chains) 200µg P.T. S.C. HIV-YU-2 Cre pseudovirus I.V. unknown 3BNC117: 0.021 unknown mIgG2a and mIgG1 D265A FcγR binding as a surrogate for Fc effector function mIgG1 and mIgG1 D265A (Fc-null) variants of bNAbs had higher rates of infection compared to mIgG2a (intact Fc function) variants of all bNAbs, suggesting that Fc-mediated effector functions play a role in protection
Jan-74 1-74: >50
3BCN60 3BNC60: 0.018
Jan-79 1-79: 24.8
3BC176 3BNC176: 1.278
PGT121 PGT121: 0.44
PG16 PG16: 0.8
Bournazos et al. (37) NRG humanized mice 3BNC117-WT Human 100µg/ml (high dose) P.T. S.C. HIV-YU-2 I.V. 57.5ng p24 0.021µg/ml >10µg/ml IgG1 FcγR binding as a surrogate for Fc effector function Mice given 3BNC117-GASDALIE (Fc enahncing) exhibited lower rates of infection compared to WT and 3BNC117-GRLR (Fc-null)
3BNC117-GRLR 20µg/ml (low dose)
3BNC117-GASDALIE
Julg et al. (10) rhesus macaques 3BNC117, PGT121 Human 10 P.T. I.V. SHIV-327c rectal challenge 300 TCID50 PGT121=0.11µg/ml ~50-150µg/ml IgG1 ADCP and CDC PGT121 protected monkeys at both doses (high dose 4/4, low dose 2/2), 3BNC117 did not protect at low dose (0/3) and only protect 1/4 monkeys at high dose, no dfference in mediating effector function
2 3BNC117=0.84µg/ml
Hangartner et al. (60) rhesus macaques PGT121 Human 1 P.T. I.V. SHIV-SF162P3 intravaginal challenge 300 TCID50   PGT121: 5-10µg/ml IgG1 ADCP and ADCC No difference in protection between PGT121 and PGT121-LALA, suggesting that effector function for this antibody maynot contribute to protection against this given virus
PGT121-LALA, PGT121-LALA: 5-18µg/ml
PGT121-LALAPG PGT121-LALAPG: 5-20µg/ml

N.A., not applicable; S.C., subcutaneous