Appendix: Table of Contents

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expressed as the concentration of IgG in ng/ml able to neutralize 90% of viral infectivity (IC90) and the reactivity of the antibodies in western blot (WB) under non-.
Appendix: Table of Contents § Appendix Table S1. Selection of blood donors § Appendix Table S2. Summary of all the genetic and functional characteristics of the panel of 21 isolated human RABV neutralizing antibodies. § Appendix Table S3. Summary of the 42 RABV isolates tested in this study. § Appendix Table S4. Summary of the characteristics of the 71 lyssaviruses tested in this study. § Appendix Table S5. Geographic distribution of the antigenic site I and III polymorphisms of the 2566 RABV isolates analyzed. § Appendix Figure S1. Neutralization of CVS-11 RABV by RVC20 and RVC58 antibodies combinations.

LBV

SHIBV

MOKV

WCBV

IRKV

EBLV$2

$ $ 130 195 544 212 136 169 77 199 351 208 115 38 43 270 325 1022 $ 34 172 2209 $ 661 157 541 $ $ $ 29 $ 27 206 625 $ 35 328 225 101 212 38 47 29 77 48565 637 10769 194 $ 57 419 34880 $ 40 20 24 $ $ 108 94

ARAV

138 2811 6755 1682 735 2391 188 630 564 $ 1411 50 94 47 $ $ 167 $ 483 $ $ 135 3606 6083 72 929 $ 31 $ 148

KHUV

10943 259 9143 782 56911 1347 978 346 751 $ 18735 507 3422 621 8087 441 7463 731 2155 46 30125 94 23126 75 27790 110 5339 $ 258 47 1120 $ 3834 145 2661 56 401 147 3124 64 365 117 26957 128 10875 171 3705 176 117 68 $ 941 26734 62 1613 78 1074 29 3137 78

EBLV$1

DUVV

ABLV

CVS$11 Berirab 907 RVA 6056 RVB 18577 RVC 1486 RVD 3307 RVE 2524 6 1028 9 1354 10 2235 17 511 20 4690 25 565 27 782 31 165 37 169 49 178 50 2463 51 398 56 1185 57 343 58 373 64 867 66 62256 67 32280 75 1119 79 $ 82 226 86 421 88 438 89 682

143 2727 2543 2400 1063 2017 40 66 1220 31 1308 123 79 34 49 58 124 63 357 86 111 173 862 110 111 32 82 59 51 35

278 1074 6209 372 396 953 199 375 1045 116 862 149 373 $ 272 102 447 236 412 144 173 162 1016 431 96 24 92 103 170 489

$ 452 104 97 $ 246 $ $ $ 24 18 $ $ $ $ 77 $ $ $ $ $ $ $ $ $ $ $ $ 93 $

$ 76 193 30 $ 28 $ $ 17 $ 28 $ $ $ $ $ $ $ 64 $ $ $ $ $ $ $ $ $ $ $

23 64 448 26 42 159 70 $ 697 45 396 $ $ 48 71 $ $ $ 42 $ 32 43 89 119 18 $ $ $ 37 46

$ $ 34 32 $ 32 $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $

Appendix Table S1. Selection of blood donors. Neutralization of 12 different pseudotypes lyssaviruses by a panel of 29 plasma samples from RABV vaccinees expresses as ID50 titers.

Isotype Donor CR057 CR4098 RAB1

HEAVY CHAIN VH

IgG1 λ IgG1 κ

V1-69*01 V3-33*03

% nts

JH

% nts

na na

J5*02 J4*02

na na

CVS-11 ppneutralization

LIGHT CHAIN DH D3-10*02 D6-19*01

HCDR3 lenght na na

VL/VK VL2-11*02 VK1-17*01

% nts na na

JL/JK

% nts

JL2*01 JK1*01

na na

(IC90 ng/ml) 1 8

Neutralization potency ratio vs Berirab

WB

987 123

Nonred. ++ ++

folds

Red. -

IgG1 κ

V3-33*03

na

J4*02

na

D6-6*01

na

VK3D-11*02

na

JK1*01

na

49

20

ND

ND

RVA122 RVA144 RVA125

A A A

IgG1 λ IgG3 λ IgG1 κ

V4-59*03 V4-39*01 V2-5*10

95% 92% 96%

J6*02 J5*02 J4*02

89% 84% 90%

D4-17*01 D4-4*01 D6-13*01

17 12 15

VL1-47*01 VL1-40*01 VK1-12*01

94% 97% 97%

JL3*02 JL2*01 JK4*01

92% 92% 100%

0,03 0,09 0,5

32900 10967 1974

+ + +

-

RVB185

B

IgG1 λ

V4-39*01

89%

J4*02

85%

D3-9*01

11

VL1-44*01

95%

JL3*02

97%

0,3

3290

++

-

RVB492 RVB143

B B

IgG1 λ IgG1 λ

V3-23*01 V1-46*01

90% 93%

J4*02 J6*02

98% 90%

D3-10*01 D2-21*01

18 20

VL-2-11*01 VL2-14*01

97% 94%

JL2*01 JL2*01

97% 84%

0,2 317

4935 3

++

+

RVB161 RVB181

B B

IgG1 λ IgG3 λ

V4-39*07 V3-30*02

96% 91%

J4*02 J6*02

88% 82%

D4-17*01 D1-26*01

14 15

VL1-44*01 VL1-40*01

98% 94%

JL3*02 JL2*01

100% 89%

0,08 1,4

12338 705

+

-

RVB686 RVC03

B C

IgG1 κ IgG1 κ

V3-30*04 V3-23*01

95% 91%

J2*01 J4*02

94% 94%

D6-6*01 D3-3*01

15 16

VK1-5*01 VK1-44*01

93% 96%

JK1*01 JK3*02

97% 97%

0,6 1

1645 987

+ +

-

RVC20 RVC21

C C

IgG3 κ IgG3 λ

V4-31*06 V4-39*01

96% 93%

J4*02 J5*01

90% 80%

D3-3*01 D4-17*01

16 13

VK1-16*01 VL1-51*01

98% 96%

JK4*01 JL1*01

100% 100%

0,1 0,04

9870 24675

++ +

-

RVC38 RVC44

C C

IgG3 κ IgG3 κ

V1-69*06 V3-21*01

91% 92%

J4*02 J3*02

85% 86%

D5-24*01 D6-19*01

14 17

VK1-9*01 VK1-39*01

96% 95%

JK4*04 JK1*01

100% 100%

0,01 0,7

98700 1410

++

+

RVC58 RVC68

C C

IgG1 λ IgG1 κ

V3-23*04 V4-59*01

96% 93%

J6*02 J6*03

95% 89%

D2-15*01 D4-17*01

17 14

VL2-14*01 VK1-12*01

99% 96%

JL2*01 JK2*01

94% 94%

0,01 9

98700 110

+

+

RVC111 RVC04

C C

IgG1 κ IgG3 λ

V3-30*04 V3-30*03

98% 95%

J4*02 J6*02

94% 77%

D1-14*01 D1-7*01

13 15

VK1-5*01 VL1-40*01

96% 96%

JK1*01 JL3*01

95% 97%

0,6 0,02

1645 49350

+

-

RVC56 RVC69

C C

IgG3 κ IgG3 κ

V3-7*01 V1-69*01

98% 92%

J6*02 J4*02

98% 92%

D3-10*01 D5-24*01

20 16

VK-1*5*03 VK1-9*01

98% 94%

JK2*01 JK4*01

97% 95%

0,03 0,13

32900 7592

ND

-

RVD74

D

IgG1 λ

V3-48*02

94%

J4*02

98%

D5-5*01

21

VL2-14*01

92%

JL2*01

91%

0,03

32900

++

-

Appendix Table S2. Summary of all the genetic and functional characteristics of the panel of 21 isolated human RABV neutralizing antibodies. Shown are VH, VL and VK usage, the percentage of nucleotide identity to the corresponding germline gene, the neutralization potency on CVS-11 RABV pseudoviruses expressed as the concentration of IgG in ng/ml able to neutralize 90% of viral infectivity (IC90) and the reactivity of the antibodies in western blot (WB) under nonreducing or reducing conditions.

63 15 7 855 262 4 515 56 41 74 55 378 678 969 96 520

83 6 27 3524 2376 445 43 24 130 33 18 43 60 11 31 1571

5 10 13 908 483 1 3.79 ND ND 4.94 3 30 460 73 4153

13/16/ 1171, 56/440 2841 4,20 0.1 20, 0.1 8/4 7 21 6 20 10 2,23 7 21 0.3 21 21,5 12,8 13,9 15,1 3,1