TABLE 2.
Comparison of neutralizing antibody titers using prototype DENV, ChimeriVax-DENV, and ChimeriVax-DENV parental strains in PRNT90
| Specimen type (no. of samples) | Specimen no. | Neutralizing antibody titers in PRNT90a
|
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prototype DENV
|
ChimeriVax-DENV
|
ChimeriVax-DENV parental strains
|
|||||||||||
| DENV1 | DENV2 | DENV3 | DENV4 | DENV1 | DENV2 | DENV3 | DENV4 | DENV1 | DENV2 | DENV3 | DENV4 | ||
| DENV1 infection (15) | 1 | 1,280 | — | — | — | 5,120 | 40 | — | — | 160 | — | — | — |
| 2 | 1,280 | 40 | — | — | 640 | 40 | 20 | — | 160 | — | 20 | — | |
| 3 | 640 | — | — | — | 80 | 20 | — | — | 160 | — | — | — | |
| 4 | 160 | — | — | — | 320 | — | — | — | 20 | — | — | — | |
| 5 | 160 | — | — | — | 160 | — | — | — | 160 | — | — | — | |
| 6 | 160 | — | — | — | 80 | — | — | — | 80 | — | — | — | |
| 7 | 320 | — | — | — | 2,560 | 40 | 40 | 20 | 320 | — | — | — | |
| 8 | 1,280 | — | 40 | 20 | 320 | 80 | 80 | 20 | 640 | — | 40 | — | |
| 9 | 40 | — | — | — | 40 | — | — | — | 40 | — | — | — | |
| 10 | 320 | — | — | — | 640 | — | — | — | 160 | — | — | — | |
| 11 | 320 | — | — | 20 | 640 | 20 | 20 | — | 320 | — | 20 | — | |
| 12 | 640 | 40 | 20 | 20 | 1,280 | 80 | 40 | — | 640 | — | 20 | — | |
| 13 | 80 | ND | ND | ND | 160 | ND | ND | ND | 160 | ND | ND | ND | |
| 14 | 40 | — | — | — | 640 | 20 | — | — | 160 | — | — | — | |
| 15 | 20 | — | — | — | 80 | 20 | — | — | 40 | — | — | — | |
| DENV2 infection (12) | 16 | 20 | 320 | — | — | — | 640 | — | — | — | 160 | — | — |
| 17 | 40 | 160 | — | — | — | 320 | — | — | — | 80 | — | — | |
| 18 | 40 | 640 | — | — | — | 640 | 20 | — | — | 320 | — | — | |
| 19 | 160 | 640 | 20 | — | 40 | 640 | 40 | 40 | 20 | 320 | 20 | — | |
| 20 | 40 | 320 | — | — | — | 320 | — | — | — | 80 | — | — | |
| 21 | — | 80 | — | — | — | 160 | — | — | — | 80 | — | — | |
| 22 | — | 160 | — | — | — | 320 | — | — | — | 320 | — | — | |
| 23 | 20 | 320 | — | 20 | — | 320 | 20 | — | — | 160 | 20 | — | |
| 24 | 20 | 320 | — | — | — | 1,280 | — | — | 20 | 160 | — | — | |
| 25 | — | 160 | — | — | — | 640 | — | — | — | 40 | — | — | |
| 26 | — | 320 | — | — | — | 1,280 | — | — | — | 320 | — | — | |
| 27 | — | 640 | — | — | — | 1,280 | — | — | — | 320 | — | — | |
| DENV3 infection (3) | 28 | — | — | — | — | — | — | — | — | — | — | — | — |
| 29 | — | — | 40 | — | — | — | 40 | — | — | — | 80 | — | |
| 30 | 20 | — | 160 | — | 20 | — | 320 | — | — | — | 160 | — | |
| DENV4 infection (3) | 31 | — | — | — | 1,280 | — | — | — | 160 | — | — | — | 320 |
| 32 | — | 20 | — | 320 | — | 20 | — | 160 | — | — | — | 320 | |
| 33 | — | 40 | — | 5,120 | — | 20 | — | 2,560 | — | — | — | 5,120 | |
| Secondary DENV infection (3) | 34 | 1,280 | 640 | 640 | 640 | 640 | 1,280 | 320 | 640 | 1,280 | 320 | 640 | 80 |
| 35 | 5,120 | 2,560 | 5,120 | 5,120 | 5,120 | 10,240 | 2,560 | 5,120 | 5,120 | 1,280 | 10,240 | 1,280 | |
| 36 | 10,240 | 5,120 | 10,240 | 40,960 | 5,120 | 20,480 | 5,120 | 40,960 | 10,240 | 2,560 | 20,480 | 10,240 | |
| WNV infection (3) | 37-39 | — | — | — | — | — | — | — | — | — | — | — | — |
| YFV vaccinated (3) | 40-42 | — | — | — | — | — | — | — | — | — | — | — | — |
| All flavivirus negative (6) | 43-48 | — | — | — | — | — | — | — | — | — | — | — | — |
| Positive controlsb | |||||||||||||
| DENV1 | 640 (5,120) | (80) | (160) | (80) | 2,560 (2,560) | (80) | (320) | (160) | 1,280 (320) | (20) | (40) | (—) | |
| DENV2 | (320) | 1,280 (1,280) | (80) | (160) | (160) | 2,560 (2,560) | (160) | (80) | (—) | 640 (80) | (—) | (—) | |
| DENV3 | (320) | (160) | 1,280 (1,280) | (160) | (320) | (160) | 640 (2,560) | (80) | (80) | (40) | 1,280 (320) | (—) | |
| DENV4 | (160) | (80) | (80) | 5,120 (5,120) | (160) | (80) | (80) | 2,560 (2,560) | (—) | (—) | (—) | 1,280 (80) | |
| Negative controlc | — | — | — | — | — | — | — | — | — | — | — | — | |
The neutralizing antibody titer is expressed as the reciprocal of the endpoint serum dilution that neutralized the challenge virus plaque count by 90%. LLOQ has a neutralizing antibody titer of 20; only positive titers (≥20) are shown. Dash = no detectable titer (<20). A neutralizing titer difference of more than fourfold between antibody to the homologous DENV serotype and antibodies to the other DENV serotypes indicates a DENV serotype-specific antibody response. The neutralizing antibody titers in parentheses are the results of the initial evaluations of the MHIAF samples using each of the four DENV serotypes as challenge viruses. These titers are shown to illustrate the level of cross-reactivity of the MHIAF samples to the other DENV serotypes. ND, not done due to insufficient sample volume.
MHIAF produced against a single DENV serotype.
Normal human control serum.