Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Blood Samples from Vaccinated Individuals
2.2. HLA Typing
2.3. MHC Class II Binding Predictions and Peptide Selection
2.4. In Vitro Expansion of YFV-Specific T Cells
2.5. Ex Vivo IFNγ ELISPOT Assay
2.6. YFV-CD4 Megapool Design and Manufacture
2.7. Flow Cytometry
2.8. Statistical Analysis
3. Results
3.1. Selection of a Panel of DRB1 Alleles that Affords High Population Coverage
3.2. Identification of Yellow Fever Epitopes
3.3. CD4+ T Cells Recognize both Structural and Non-Structural Proteins
3.4. Magnitude of Responses Varies as a Function of HLA
3.5. Development and Validation of a CD4+ Yellow Fever Epitope Mega Pool
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sequence | Protein | Position | Total SFC (106 PBMCs) | Cumulative % Total | HLA Recognized | HLA Restriction(s) |
---|---|---|---|---|---|---|
VRRGVRSLSNKIKQK | C | 16 | 7333 | 5.4 | 4 | DRB1*04:03, DRB1*08:02, DRB1*15:01, DRB1*16:02 |
LMRRMRRPTGKVTLE | NS5 | 2746 | 6330 | 10.0 | 4 | DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:02 |
QTSRLLMRRMRRPTG | NS5 | 2741 | 5313 | 13.8 | 5 | DRB1*08:02, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:02 |
ILAECARRRLRTLVL | NS3 | 1696 | 4983 | 17.5 | 1 | DRB1*16:02 |
VVVLNRKTFEREYPT | NS3 | 1871 | 4873 | 21.0 | 2 | DRB1*11:04, DRB1*13:01 |
LRKVKRVVASLMRGL | C | 81 | 4587 | 24.4 | 4 | DRB1*01:01, DRB1*04:03, DRB1*11:01, DRB1*11:04 |
GEVIGLYGNGILVGD | NS3 | 1631 | 3757 | 27.1 | 2 | DRB1*15:01, DRB1*15:02 |
RFLPQILAECARRRL | NS3 | 1691 | 3480 | 29.7 | 2 | DRB1*04:07, DRB1*10:01 |
QGLAVLRKVKRVVAS | C | 76 | 2893 | 31.8 | 4 | DRB1*08:02, DRB1*11:01, DRB1*11:04, DRB1*13:01 |
DMRLLSLAVSSAVPT | NS5 | 3281 | 2793 | 33.8 | 4 | DRB1*04:07, DRB1*07:01, DRB1*11:01, DRB1*13:01 |
KAGKSVVVLNRKTFE | NS3 | 1866 | 2773 | 35.8 | 2 | DRB1*11:04, DRB1*13:01 |
GVTLVRKNRWLLLNV | M | 121 | 2693 | 37.8 | 3 | DRB1*08:02, DRB1*13:01, DRB1*15:01 |
SLASVAMCRTPFSLA | NS4B | 2436 | 2530 | 39.7 | 4 | DRB1*04:03, DRB1*04:07, DRB1*10:01, DRB1*11:04 |
NNGGDAMYMALIAAF | NS2A | 1196 | 2523 | 41.5 | 1 | DRB1*13:01 |
ITAHLKRLWKMLDPR | C | 61 | 2400 | 43.2 | 2 | DRB1*11:01, DRB1*11:04 |
VRKVCYNAVLTHVKI | E | 341 | 2393 | 45.0 | 3 | DRB1*04:07, DRB1*10:01, DRB1*11:04 |
GSIVACAKFTCAKSM | E | 396 | 2353 | 46.7 | 2 | DRB1*11:04, DRB1*13:01 |
NNLYKLHGGHVSCRV | E | 556 | 2287 | 48.4 | 1 | DRB1*01:01 |
LLIGFGLRTLWSPRE | NS2A | 1216 | 2233 | 50.0 | 2 | DRB1*13:01, DRB1*15:01 |
GFIFFFLFNILTGKK | C | 46 | 2227 | 51.6 | 5 | DRB1*01:01, DRB1*04:01, DRB1*07:01, DRB1*11:01, DRB1*15:02 |
VVVQDPKNVYQRGTH | NS1 | 866 | 2123 | 53.2 | 2 | DRB1*03:01, DRB1*13:01 |
RVVASLMRGLSSRKR | C | 86 | 2087 | 54.7 | 2 | DRB1*04:03, DRB1*13:01 |
GNTSLLWNGPMAVSM | NS4B | 2466 | 2027 | 56.2 | 1 | DRB1*01:01 |
KIERWFVRNPFFAVT | M | 241 | 1960 | 57.6 | 2 | DRB1*15:02, DRB1*16:02 |
EVDISVVVQDPKNVY | NS1 | 861 | 1957 | 59.0 | 1 | DRB1*13:01 |
FVGVMYNLWKMKTGR | NS4B | 2491 | 1900 | 60.4 | 2 | DRB1*11:01, DRB1*11:04 |
LIWVGINTRNMTMSM | E | 746 | 1790 | 61.7 | 3 | DRB1*04:01, DRB1*10:01, DRB1*13:01 |
GTRKIMKVVNRWLFR | NS5 | 2876 | 1720 | 63.0 | 1 | DRB1*15:01 |
DGDSYYYSEPTSENN | NS3 | 1956 | 1610 | 64.2 | 1 | DRB1*04:01 |
PKNVYQRGTHPFSRI | NS1 | 871 | 1600 | 65.3 | 1 | DRB1*16:02 |
FLFNILTGKKITAHL | C | 51 | 1573 | 66.5 | 2 | DRB1*01:01, DRB1*11:01 |
DEQEILNYMSPHHKK | NS5 | 3056 | 1513 | 67.6 | 3 | DRB1*04:01, DRB1*15:01, DRB1*15:06 |
LPSIRAANVMAASLR | NS3 | 1851 | 1437 | 68.6 | 5 | DRB1*04:01, DRB1*04:03, DRB1*04:07, DRB1*07:01, DRB1*11:04 |
GAFLVRNGKKLIPSW | NS3 | 1541 | 1413 | 69.7 | 3 | DRB1*11:01, DRB1*13:01, DRB1*16:02 |
GVIMMFLSLGVGADQ | E | 766 | 1313 | 70.6 | 2 | DRB1*11:01, DRB1*15:01 |
QYVIRAQLHVGAKQE | E | 421 | 1270 | 71.5 | 1 | DRB1*16:02 |
VSMMIAMEVVLRKRQ | NS2A | 1141 | 1243 | 72.5 | 3 | DRB1*04:03, DRB1*13:01, DRB1*16:02 |
HATLTYRMLEPTRVV | NS3 | 1751 | 1213 | 73.3 | 2 | DRB1*01:01, DRB1*10:01 |
RWLFRHLAREKNPRL | NS5 | 2886 | 1140 | 74.2 | 1 | DRB1*13:01 |
FIAKVRSHAAIGAYL | NS5 | 2906 | 1127 | 75.0 | 3 | DRB1*01:01, DRB1*04:03, DRB1*04:07 |
HLA DRB1 Allele | No. 1 | Total Response Magnitude/Donor | Average of Epitopes/Donor | C | M | E | NS1 | NS2A | NS2B | NS3 | NS4A | NS4B | NS5 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
01:01 | 3 | 4644 | 8.3 | 820 | 140 | 876 | 0 | 300 | 171 | 831 | 0 | 988 | 519 |
03:01 | 2 | 850 | 4.5 | 0 | 0 | 93 | 200 | 0 | 0 | 413 | 0 | 47 | 97 |
04:01 | 5 | 2280 | 4.6 | 179 | 0 | 297 | 0 | 0 | 64 | 1211 | 116 | 213 | 199 |
04:03 | 3 | 2093 | 3.3 | 1307 | 0 | 38 | 0 | 160 | 0 | 98 | 0 | 322 | 169 |
04:05 | 1 | 0 | 0.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
04:07 | 3 | 2577 | 4.3 | 0 | 0 | 647 | 0 | 51 | 0 | 1080 | 164 | 351 | 283 |
07:01 | 3 | 984 | 1.7 | 29 | 0 | 76 | 0 | 0 | 0 | 180 | 0 | 0 | 700 |
08:02 | 1 | 2993 | 6.0 | 1320 | 87 | 0 | 0 | 0 | 0 | 320 | 0 | 0 | 1267 |
10:01 | 1 | 4560 | 13.0 | 0 | 0 | 833 | 0 | 300 | 0 | 2253 | 0 | 793 | 380 |
11:01 | 4 | 1642 | 4.8 | 180 | 0 | 313 | 0 | 0 | 58 | 125 | 38 | 73 | 854 |
11:04 | 3 | 5185 | 5.8 | 1625 | 0 | 747 | 0 | 0 | 0 | 493 | 0 | 672 | 1648 |
12:01 | 2 | 577 | 1.5 | 0 | 0 | 70 | 0 | 0 | 0 | 80 | 0 | 0 | 427 |
13:01 | 5 | 5746 | 5.6 | 889 | 453 | 314 | 784 | 1023 | 0 | 1604 | 0 | 0 | 678 |
15:01 | 8 | 1767 | 2.1 | 391 | 72 | 93 | 0 | 240 | 0 | 556 | 108 | 16 | 292 |
15:02 | 2 | 3105 | 6.5 | 57 | 893 | 0 | 0 | 0 | 0 | 182 | 237 | 182 | 1555 |
15:06 | 1 | 820 | 2.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 250 | 570 |
16:02 | 1 | 9950 | 10.0 | 573 | 320 | 1450 | 1600 | 290 | 0 | 5097 | 0 | 140 | 480 |
TOTAL | 48 | 49,773 | - | 7369 | 1965 | 5846 | 2584 | 2365 | 293 | 14,523 | 662 | 4047 | 10,117 |
% | - | 100 | - | 14.8 | 3.9 | 11.7 | 5.2 | 4.8 | 0.6 | 29.2 | 1.3 | 8.1 | 20.3 |
Mean | - | 2928 | 5 | 433 | 116 | 344 | 152 | 139 | 17 | 854 | 39 | 238 | 595 |
SD | - | 2485.9 | 3.3 | 553.9 | 238.6 | 421.6 | 420.0 | 258.4 | 44.5 | 1261.6 | 72.3 | 305.0 | 486.7 |
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Mateus, J.; Grifoni, A.; Voic, H.; Angelo, M.A.; Phillips, E.; Mallal, S.; Sidney, J.; Sette, A.; Weiskopf, D. Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees. Viruses 2020, 12, 1300. https://doi.org/10.3390/v12111300
Mateus J, Grifoni A, Voic H, Angelo MA, Phillips E, Mallal S, Sidney J, Sette A, Weiskopf D. Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees. Viruses. 2020; 12(11):1300. https://doi.org/10.3390/v12111300
Chicago/Turabian StyleMateus, Jose, Alba Grifoni, Hannah Voic, Michael A. Angelo, Elizabeth Phillips, Simon Mallal, John Sidney, Alessandro Sette, and Daniela Weiskopf. 2020. "Identification of Novel Yellow Fever Class II Epitopes in YF-17D Vaccinees" Viruses 12, no. 11: 1300. https://doi.org/10.3390/v12111300