Background
Methods
Serum samples
Determination of the levels of anti-DENV IgM and IgG antibodies by ELISA
Determination of the levels of anti-JEV IgG antibody by ELISA
Viruses and cell lines
JEV and DENV neutralization assay
Antibody-dependent enhancement (ADE) assay for DENV
Results
Increase in positive rates of anti-DENV IgG after JE vaccination
JE vaccination increased ADE activity to all four DENV serotypes
Samples | Number of serum samples that demonstrated ADE activity (Percentage of samples with ADE activity) | |||
---|---|---|---|---|
DENV-1 | DENV-2 | DENV-3 | DENV-4 | |
Pre-JE vaccination (n = 77) | 5 (6 %) | 2 (3 %) | 11 (14 %) | 10 (13 %) |
Post-JE vaccination (n = 77) | 14 (18 %) | 16 (21 %) | 24 (31 %) | 24 (31 %) |
Increase in overall ADE activity to DENV in JE vaccine recipients
ADE activity in each of the serum samples to four DENV serotypes | n | JEV NA titera | |
---|---|---|---|
(Mean JEV NA titer ± s.d.) | |||
Pre-vaccination | Post-vaccination | ||
(A) Absence of ADE activity to DENV, both before and after JE vaccination | 40 | 19 ± 29 | 153 ± 419 |
(B) Presence of ADE activity to DENV after JE vaccination only | |||
1. ADE activity to ≥3 DENV serotypes | 6 | 98 ± 124 | 1130 ± 1199 |
2. ADE activity to two DENV serotypes | 4 | 91 ± 153 | 500 ± 592 |
3. ADE activity to one DENV serotype | 10 | 47 ± 64 | 277 ± 372 |
Total | 20 | 71 ± 101b | 578 ± 803b |
(C) Presence of ADE activity to DENV both before and after JE vaccination | |||
1. ADE activity to ≥3 DENV serotypes | 10 | 96 ± 122 | 1325 ± 1644 |
2. ADE activity to two DENV serotypes | 1 | 40 | 80 |
3. ADE activity to one DENV serotype | 4 | 53 ± 74 | 341 + 346 |
Total | 15 | 81 ± 106b | 980 + 1422b |
ADE activity to DENV in undiluted serum samples after JE vaccination
Sample no. (post-JE vaccination) (n = 35)c | Fold enhancement to DENVa | ADE activity to number of DENV serotypes | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
DENV-1 | DENV-2 | DENV-3 | DENV-4 | |||||||
Undiluted | 1:10-dilution | Undiluted | 1:10-dilution | Undiluted | 1:10-dilution | Undiluted | 1:10-dilution | Undiluted | 1:10-dilution | |
3 | –b | – | – | – | – | – |
3.1
|
2.5
| 1 | 1 |
9 | – | – | – | – | – | – | 2.2 |
1.9
| 0 | 1 |
11 |
4.5
a
|
2.3
|
3.2
|
4.0
|
4.1
a
|
2.9
| 2.3 |
2.7
| 3 | 4 |
13 |
13.0
|
2.8
|
4.0
|
2.8
|
5.9
| 2.1 |
4.5
|
2.8
| 4 | 3 |
19 | – | – | – | – |
4.4
|
2.6
| – | – | 1 | 1 |
202 |
14.5
|
2.6
|
2.8
|
3.6
|
5.3
|
2.5
|
3.3
|
2.4
| 4 | 4 |
211 | – | – |
4.2
|
2.6
|
4.3
|
3.5
|
4.9
|
2.8
| 3 | 3 |
22 |
3.5
|
2.0
| – | – | – | – | – | – | 1 | 1 |
313 | 2.5 |
3.0
|
6.6
|
4.8
|
2.7
|
3.2
|
4.7
|
2.4
| 2 | 4 |
321 | – | – | – | – | 2.5 |
2.5
| – | – | 0 | 1 |
33 |
6.0
|
2.5
|
2.5
|
3.8
|
4.1
|
3.9
|
4.4
|
2.2
| 4 | 4 |
43 | – | – |
5.1
|
2.8
|
4.9
|
4.8
|
6.6
| 1.8 | 3 | 2 |
47 | – | – | – | – | 3.2 |
3.3
| 1.6 |
2.3
| 0 | 2 |
49 | – | – | – | – |
3.9
|
2.3
| – | – | 1 | 1 |
512 |
6.7
|
2.6
| – | – |
5.0
|
2.6
|
3.3
|
2.3
| 3 | 3 |
53 | – | – | – | – |
3.9
|
2.0
| – | – | 1 | 1 |
54 | – | – | – | – |
5.0
|
3.5
| – | – | 1 | 1 |
573 |
6.7
|
2.2
|
5.5
|
2.0
|
4.5
|
2.7
| 3 | 3 | ||
58 |
4.0
| 1.9 | 1.5 |
3.2
|
4.1
| 3.2 |
3.4
|
3.8
| 3 | 3 |
593 |
4.3
|
4.2
| 1.2 |
2.5
|
4.0
|
3.9
| 1.0 |
3.4
| 2 | 4 |
61 |
7.3
|
2.1
| – | – | – | – | – | – | 1 | 1 |
732 | – | – | 0.4 |
2.3
|
4.1
|
3.5
| 1.3 |
3.5
| 1 | 3 |
77 | – | – | – | – |
6.3
|
4.0
|
3.3
| 1.8 | 2 | 1 |
781 | – | – | – | – | 2.0 |
2.2
| – | – | 0 | 1 |
79 | 2.0 |
2.2
| 1.1 |
3.6
|
5.0
|
6.7
|
3.8
|
2.7
| 2 | 4 |
80 |
4.0
|
2.1
|
2.5
|
2.5
|
5.4
|
3.2
| – | – | 3 | 3 |
85 | – | – | – | – | – | – |
6.2
|
2.6
| 1 | 1 |
861 | 1.7 |
2.4
| 1.0 |
3.3
| 2.9 |
4.6
| 2.3 |
2.5
| 0 | 4 |
893 |
7.0
|
4.1
|
4.2
|
2.0
|
4.8
|
5.1
|
3.3
|
3.3
| 4 | 4 |
93 | – | – | – | – | 3.1 |
3.2
| 1.9 |
2.4
| 0 | 2 |
941 | – | – | – | – | – | – |
5.8
|
2.6
| 1 | 1 |
951 | – | – | – | – | – | – | 2.1 |
2.1
| 0 | 1 |
961 | – | – |
4.0
|
2.0
|
3.8
|
3.1
|
3.8
|
5.2
| 3 | 3 |
100 | – | – | – | – | – | – | 2.4 |
2.1
| 0 | 1 |
110 | – | – | – | – |
4.9
|
2.8
|
3.4
|
2.2
| 2 | 2 |
Total number of samples | 12 | 14 | 11 | 16 | 20 | 24 | 17 | 24 |