Table 5. Immunogenicity of the pan-DENV sequences in HLA-DR transgenic mice.
DENV protein | Pan-DENV sequenceb | Ag-specific CD4 T-cell responsesa | |||
Peptide sequences (DENV-3)c | IFN-γ-SFC/106splenocytes±SDd | ||||
DR2 | DR3 | DR4 | |||
E | 252VLGSQEGAMH261 | PEVVVLGSQEGAMHT | - | - | 88±34 |
NS1 | 193AVHADMGYWIES204 | AVHADMGYWIESQKN | - | 17±1 | - |
229HTLWSNGVLES239 | WPKSHTLWSNGVLES | - | 129±3* | - | |
HTLWSNGVLESDMII | - | 131±103 | 37±3 | ||
266GPWHLGKLE274 | HTQTAGPWHLGKLE | - | 333±6 | - | |
294RGPSLRTTT302 | TRGPSLRTTTVSGKL | - | - | 11±4 | |
NS3 | 189LTIMDLHPG197 | KKRNLTIMDLHPGSG | - | - | 50±16 |
296AARGYISTRV305 | ASIAARGYISTRVGM | 40±14 | - | - | |
ARGYISTRVGMGEAA | 9±4 | - | - | ||
313IFMTATPPG321 | EAAAIFMTATPPGTA | - | - | 474±116 | |
IFMTATPPGTADAFP | - | - | 323±287 | ||
357GKTVWFVPSIK367 | TDFAGKTVWFVPSIK | 48±15 | - | - | |
GKTVWFVPSIKAGND | 396±14 | - | - | ||
383VIQLSRKTFD392 | KKVIQLSRKTFDTEY | - | 21±3 | - | |
406VVTTDISEMGANF418 | FVVTTDISEMGANFK | - | - | 408±104 | |
TDISEMGANFKADRV | - | 152±33 | - | ||
NS5 | 302TWAYHGSYE310 | DENPYKTWAYHGSYEVK | 126±10* | - | 14±5 |
TWAYHGSYEVKATGSA | 161±20* | - | 63±17 | ||
342AMTDTTPFGQQRVFKEKVDTRT363 | MVTQMAMTDTTPFGQQR | - | - | 28±0* | |
450CVYNMMGKREKKLGEFG466 | GSCVYNMMGKREKKLGE | - | - | 13±2 | |
505SGVEGEGLH513 | NSYSGVEGEGLHKLGYI | - | - | 184±15 | |
531YADDTAGWDTRIT543 | KIPGGAMYADDTAGWDT | - | - | 46±3 | |
568IFKLTYQNKVV578 | ANAIFKLTYQNKVVKVQ | 577±384 | - | 24±9* | |
597DQRGSGQVGTYGLNTFTNME616 | VMDIISRKDQRGSGQVG | - | 88±1 | - | |
658RMAISGDDCVVKP670 | VERLKRMAISGDDCVVK | - | 159±24 | 16±6 | |
MAISGDDCVVKPIDDRF | - | 249±39 | - | ||
707VPFCSHHFH715 | DWQQVPFCSHHFHELIM | 32±8* | 34±11 | - | |
765LMYFHRRDLRLA776 | MYFHRRDLRLASNAI | 75±16* | - | 33±9 | |
790PTSRTTWSIHA800 | VHWVPTSRTTWSIHAHH | - | - | 83±1 | |
SRTTWSIHAHHQWMTTE | - | - | 122±46 |
Assessed by IFN-γ ELISpot assay in HLA-DR2 (DRB1*1501), HLA-DR3 (DRB1*0301) and HLA-DR4 (DRB1*0401) Tg mice immunized with DENV-3 peptides (see Methods)
Amino acid positions numbered according to the sequence alignments of the 4 DENV types
Sequences present in the pan-DENV sequences are underlined
SFC, spot-forming cells; SD, standard deviation. Representative results from at least two immunized Tg mice are shown, except when indicated by an asterisk