Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. HLA Class II Transgenic Mice
2.3. Live B. anthracis Challenge
2.4. Expression and Purification of PA Antigens
2.5. PA Epitope Mapping in Transgenic Mice
2.6. PA Epitope Mapping with Human Donor PBMC Samples
2.7. HLA-Peptide Binding Assay
3. Results
3.1. CD4+ T Cell Responses to B. anthracis PA Epitopes in Anthrax-Recovered Patients and Vaccinees
3.2. Differential Susceptibility to B. anthracis Challenge in HLA Transgenic Mice
3.3. CD4+ T Cell Responses to B. anthracis PA Epitopes in HLA Transgenic Mice
3.4. The Differential PA Peptide Binding across Distinct HLA Polymorphisms
3.5. Figures and Tables
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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PA Peptide Sequence | HLA Transgenic Strain Responding to Epitope after PA Immunisation | Human Cohort Responding to Epitope (>20% Cohort Responding) | Relative Binding of HLA Class II | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
DR1 | DR3 | DR4 | DR7 | DR11 | DR13 | DR15 | DQ6 | DQ8 | |||
21GYYFSDLNFQAPMVVTSSTT40 | - | Vaccinee, Infected | 23 | 60 | 0.3 | 22 | 53 | >1908 | 118 | ND | ND |
31APMVVTSSTTGDLSIPSSEL50 | DR4 | - | ND | ND | ND | ND | ND | ND | ND | ND | ND |
41GDLSIPSSELENIPSENQYF60 | DR1 | Infected | 3312 | >728 | 46 | 424 | >1288 | >1288 | 134 | ND | ND |
51ENIPSENQYFQSAIWSGFIK70 | DR4 | Infected | 3 | 600 | 1 | 2 | 2 | >2733 | 55 | ND | ND |
61QSAIWSGFIKVKKSDEYTFA80 | - | Infected | 617 | 12 | 650 | 89 | 14 | 4 | 1 | ND | ND |
71VKKSDEYTFATSADNHVTMW90 | DR4 | Infected | 11 | 8 | 1 | 2 | 118 | >2733 | 45 | ND | ND |
91VDDQEVINKASNSNKIRLEK110 | - | Infected | 1333 | 283 | 992 | 36 | >1357 | 245 | 164 | ND | ND |
121QRENPTEKGLDFKLYWTDSQ140 | DR4 | Infected | >2563 | 800 | 6 | 1549 | >1357 | >2733 | 119 | ND | ND |
141NKKEVISSDNLQLPELKQKS160 | DQ8 | Infected | 131 | 26 | 48 | 28 | 849 | >2733 | 1 | >3054 | >166 |
148SDNLQLPELKQKSSNSRKKR167 | - | Infected | ND | ND | ND | ND | ND | ND | ND | ND | ND |
151LQLPELKQKSSNSRKKRSTS170 | DQ8 | Infected | >6667 | >667 | >1788 | >1543 | 701 | 177 | >511 | >3054 | >166 |
161SNSRKKRSTSAGPTVPDRDN180 | - | Infected | >6667 | >667 | >1788 | >1543 | >1336 | >1908 | >511 | ND | ND |
168STSAGPTVPDRDNDGIPDSL187 | - | Infected | >6667 | >667 | >1788 | >1543 | >1336 | >1908 | >511 | ND | ND |
171AGPTVPDRDNDGIPDSLEVE190 | - | Infected | 149 | 211 | 10 | 1167 | 7 | 51 | 95 | ND | ND |
191GYTVDVKNKRTFLSPWISNI210 | DQ8 | Infected | 216 | 0.2 | 190 | 11 | 231 | 0.5 | 15 | 2488 | >166 |
201TFLSPWISNIHEKKGLTKYK220 | DQ8 | - | 3162 | >667 | 1400 | 873 | 327 | 306 | 14 | 3077 | >166 |
221SSPEKWSTASDPYSDFEKVT240 | DR4 | - | ND | ND | ND | ND | ND | ND | ND | ND | ND |
241GRIDKNVSPEARHPLVAAYP260 | DQ8 | Vaccinee, Infected | 2828 | 15 | 55 | 833 | 567 | 9 | 9 | 899 | >166 |
261IVHVDMENIILSKNEDQSTQ280 | - | Infected | >6667 | >667 | 167 | >1543 | >1336 | >1908 | >511 | ND | ND |
281NTDSETRTISKNTSTSRTHT300 | - | Infected | >6667 | 23 | 179 | 707 | 535 | 60 | >511 | ND | ND |
301SEVHGNAEVHASFFDIGGSV320 | DQ8 | Vaccinee, Infected | >6667 | >667 | >1788 | 327 | >1336 | >1908 | >511 | 3 | 7 |
321SAGFSNSNSSTVAIDHSLSL340 | DR4 | Infected | 279 | 1 | 6 | 0.4 | 935 | >1908 | 95 | ND | ND |
331TVAIDHSLSLAGERTWAETM350 | DR4, DQ8 | Infected | 176 | 0.3 | 10 | 11 | 30 | 4 | 120 | 1056 | 0.1 |
361NANIRYVNTGTAPIYNVLPT380 | DR1 | Vaccinee, Infected | 15 | >728 | 0.4 | 1 | 12 | >1288 | 3 | ND | ND |
371TAPIYNVLPTTSLVLGKNQT390 | DR1, DR4 | Infected | 1 | 12 | 2 | 0.4 | 78 | 300 | 6 | ND | ND |
391LATIKAKENQLSQILAPNNY410 | - | Infected | 89 | 176 | 7 | 179 | 46 | 43 | 0.2 | ND | ND |
421LNAQDDFSSTPITMNYNQFL440 | - | Infected | >6667 | >667 | 1265 | 22 | >1336 | >1908 | 77 | ND | ND |
431PITMNYNQFLELEKTKQLRL450 | - | Vaccinee, Infected | 15 | 25 | 38 | 1 | 2 | 7 | 0.1 | ND | ND |
451DTDQVYGNIATYNFENGRVR470 | DR4 | Infected | 200 | >667 | 293 | 30 | >1336 | >1908 | 2 | ND | ND |
461TYNFENGRVRVDTGSNWSEV480 | DR4 | - | ND | ND | ND | ND | ND | ND | ND | ND | ND |
481LPQIQETTARIIFNGKDLNL500 | DQ8 | Infected | 2 | 5 | 886 | 0.3 | 37 | 2 | 1 | 240 | 6 |
491IIFNGKDLNLVERRIAAVNP510 | DQ8 | - | 3801 | 31 | 327 | 267 | 0.1 | 7 | 95 | 693 | 75 |
501VERRIAAVNPSDPLETTKPD520 | DQ8 | Vaccinee, Infected | 721 | 75 | 69 | 55 | >1288 | >1288 | 145 | 2506 | 29 |
511SDPLETTKPDMTLKEALKIA530 | - | Infected | 211 | 10 | 1800 | 401 | 1000 | 10 | 37 | ND | ND |
521MTLKEALKIAFGFNEPNGNL540 | - | Infected | 1155 | 18 | >1788 | 98 | 189 | 10 | 77 | ND | ND |
531FGFNEPNGNLQYQGKDITEF550 | - | Infected | >6667 | >667 | 207 | >1543 | 1134 | >1908 | 63 | ND | ND |
541QYQGKDITEFDFNFDQQTSQ560 | - | Infected | >2563 | 25 | 306 | >3365 | >1357 | >2733 | 44 | ND | ND |
551DFNFDQQTSQNIKNQLAELN570 | - | Infected | 249 | 82 | 239 | 267 | >1336 | 250 | 200 | ND | ND |
561NIKNQLAELNATNIYTVLDK580 | DR1 | - | 2 | >728 | 76 | 8 | 137 | 64 | 8 | ND | ND |
571ATNIYTVLDKIKLNAKMNIL590 | - | Infected | 31 | 5 | 278 | 19 | 0.5 | 3 | 11 | ND | ND |
581IKLNAKMNILIRDKRFHYDR600 | - | Infected | 2160 | 0.1 | 500 | 378 | 6 | 0 | 4 | ND | ND |
591IRDKRFHYDRNNIAVGADES610 | DR4, DQ8 | - | 25 | 1 | 0.2 | 4 | 4 | 25 | 2 | 1132 | 0.5 |
601NNIAVGADESVVKEAHREVI620 | DR4, DQ8 | - | 4989 | 10 | 1183 | 750 | 732 | 16 | 122 | 2191 | 6 |
621NSSTEGLLLNIDKDIRKILS640 | - | Infected | 2236 | 1 | 414 | 80 | 53 | 3 | 77 | ND | ND |
631IDKDIRKILSGYIVEIEDTE650 | DR1 | Infected | 5 | 775 | 510 | 1 | 72 | 1026 | 0.3 | ND | ND |
641GYIVEIEDTEGLKEVINDRY660 | DR4 | - | 3162 | 82 | 21 | 65 | 433 | 1333 | 0.1 | ND | ND |
651GLKEVINDRYDMLNISSLRQ670 | DQ8 | Infected | 7 | 10 | 6 | 22 | 46 | 15 | 6 | >3054 | 1 |
661DMLNISSLRQDGKTFIDFKK680 | - | Infected | 200 | 2 | 30 | 27 | 33 | 4 | 27 | ND | ND |
671DGKTFIDFKKYNDKLPLYIS690 | - | Vaccinee, Infected | 2494 | 100 | >1788 | 138 | 14 | 25 | 4 | ND | ND |
681YNDKLPLYISNPNYKVNVYA700 | DR1, DR4 | Infected | 1 | 4 | 1 | 2 | 2 | 30 | 1 | ND | ND |
691NPNYKVNVYAVTKENTIINP710 | - | Infected | 50 | 3 | 75 | 0.3 | 13 | 6 | 10 | ND | ND |
711SENGDTSTNGIKKILIFSKK730 | DR4, DQ8 | - | >6667 | >667 | >1788 | 133 | 3 | 217 | 3 | >3054 | >166 |
716TSTNGIKKILIFSKKGYEIG735 | DQ8 | - | 183 | 1 | 849 | 35 | 0.4 | 0.4 | 1 | >3054 | >166 |
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Ascough, S.; Ingram, R.J.; Chu, K.K.Y.; Moore, S.J.; Gallagher, T.; Dyson, H.; Doganay, M.; Metan, G.; Ozkul, Y.; Baillie, L.; et al. Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection. Vaccines 2022, 10, 1571. https://doi.org/10.3390/vaccines10101571
Ascough S, Ingram RJ, Chu KKY, Moore SJ, Gallagher T, Dyson H, Doganay M, Metan G, Ozkul Y, Baillie L, et al. Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection. Vaccines. 2022; 10(10):1571. https://doi.org/10.3390/vaccines10101571
Chicago/Turabian StyleAscough, Stephanie, Rebecca J. Ingram, Karen K. Y. Chu, Stephen J. Moore, Theresa Gallagher, Hugh Dyson, Mehmet Doganay, Gökhan Metan, Yusuf Ozkul, Les Baillie, and et al. 2022. "Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection" Vaccines 10, no. 10: 1571. https://doi.org/10.3390/vaccines10101571