Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups
Abstract
:1. Introduction
2. Materials and Methods
2.1. SARS-CoV-2 Peptide Prediction and Selection
2.2. Self-Administered Vaccination
2.3. Ethical and Scientific Considerations
2.4. Immunomonitoring
3. Results
3.1. Clinical Aspect of the Vaccination Sites
3.2. T Cell Responses
3.3. Antibody Responses
4. Discussion
- CD4 Th1 cells should vigorously activate virus antigen-experienced B cells that should already pre-exist in most COVID-19-patients. An illustration for this assumption is provided in Figure 1. These CD4 T cells would be expected to directly contribute to virus clearance and deliver strong T helper signals to the CD8 T cells already primed during natural infection. The resulting enhanced activity could lead to more rapid virus clearance or transiently increased lung damage.
- Vaccine-induced CD8 T cells against peptides embedded in the longer peptides do appear later, as preliminary data from the majority of subjects in our presently running study suggest (https://clinicaltrials.gov, accessed on 20 April 2021, Identifier: NCT04546841). In this study, six immunodominant 15-mer peptides reported in [16] are used in a vaccine with Montanide and XS15. Once activated, such CD8 T cells should also contribute to faster virus clearance.
- Vaccine-induced antibodies against the viral peptides tested in this study might also appear much later, if at all.
- Since we found IFNγ-producing T cells, we conclude that Th1 CD4 T cells were induced. Therefore, there should be no disease enhancing-effects related to the induction of Th2-bias, as described for other coronaviruses [21].
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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AA Sequence | Predicted HLA Restriction | Source Protein | Peptide ID | AA Position | Peptide Length | Administered Amount (μg) |
---|---|---|---|---|---|---|
SPDDQIGYY | A*01 | SARS-CoV-2 nuc | nuc-A1-1 | 79–87 | 9 | 240 |
MKDLSPRWY | A*01 | nuc-A1-2 | 101–109 | 9 | 240 | |
LLLDRLNQL | B*08 | nuc-B8-1 | 222–230 | 9 | 240 | |
IGYYRRATRRIRGGD | DR | nuc-DR-1 | 84–98 | 15 | 240 | |
ASAFFGMSRIGMEVT | DR | nuc-DR-2 | 311–325 | 15 | 240 | |
VSLVKPSFY | A*01 | SARS-CoV-2 env | env-A1-1 | 49–57 | 9 | 720 |
YVYSRVKNL | B*08 | env-B8-1 | 57–65 | 9 | 720 | |
FYVYSRVKNLNSSRV | DR | env-DR-1 | 56–70 | 15 | 240 | |
YSEHPTFTSQY | A*01 | CMV-pp65 | CMV-A1-1 | 363–373 | 11 | 720 |
YQEFFWDANDIYRIF | DR | CMV-DR-1 | 510–524 | 15 | 240 |
AA Sequence | Source Protein | Peptide ID | AA Position | Peptide Length |
---|---|---|---|---|
ASVYAWNRKRISN | SARS-CoV-2 spike | spi-DR-1 | 348–360 | 13 |
VADYSVLYNSASFST | spi-DR-2 | 362–376 | 15 | |
IGYYRRATRRIRGGD | SARS-CoV-2 nuc | nuc-DR-1 | 84–98 | 15 |
ASAFFGMSRIGMEVT | nuc-DR-2 | 311–325 | 15 | |
RWYFYYLGTGPEAGL | nuc-DR-5 | 107–121 | 15 | |
ASWFTALTQHGKEDL | nuc-DR-6 | 50–64 | 15 | |
LLLLDRLNQLESKMS | nuc-DR-7 | 221–235 | 15 | |
AADLDDFSKQLQQSM | nuc-DR-8 | 397–411 | 15 | |
AIVLQLPQGTTLPKG | nuc-DR-9 | 156–170 | 15 | |
YKHWPQIAQFAPSAS | nuc-DR-10 | 298–312 | 15 |
AA Sequence | Source Protein | Peptide ID | IFNγ | IL-2 | CD154 | TNF |
---|---|---|---|---|---|---|
% (Fold Increase) | ||||||
IGYYRRATRRIRGGD | nuc | nuc-DR-1 | 4.2 (199) | 1.6 (35) | 16.0 (60) | 14.2 (191) |
ASAFFGMSRIGMEVT | nuc | nuc-DR-2 | 12.0 (571) | 3.2 (67) | 31.7 (118) | 24.0 (321) |
ASVYAWNRKRISN | spike | spi-DR-1 | 8.9 (424) | 4.6 (76) | 34.0 (122) | 22.0 (201) |
VADYSVLYNSASFST | spike | spi-DR-2 | 0.0 | 0.0 | −0.3 | −0.1 |
RWYFYYLGTGPEAGL | nuc | nuc-DR-5 | 0.1 (4) | 0.3 (6) | 1.3 (4) | 1.2 (12) |
ASWFTALTQHGKEDL | nuc | nuc-DR-6 | 0.0 | 0.0 | 0.1 | 0.1 |
LLLLDRLNQLESKMS | nuc | nuc-DR-7 | 16.0 (696) | 3.3 (62) | 37.1 (99) | 31.1 (312) |
AADLDDFSKQLQQSM | nuc | nuc-DR-8 | 0.0 | 0.0 | −0.1 | 0.0 |
AIVLQLPQGTTLPKG | nuc | nuc-DR-9 | 0.0 | 0.0 | 0.0 | −0.1 |
YKHWPQIAQFAPSAS | nuc | nuc-DR-10 | 0.0 | 0.0 | −0.1 | 0.0 |
Embedded AA sequence | ||||||
VYAWNRKRI * | spike | - | 1.6 (45) | 1.0 (13) | 15.8 (13) | 8.0 (22) |
SVLYNSASF * | spike | - | 4.6 (128) | 3.9 (49) | 17.6 (15) | 15.1 (41) |
LLDRLNQL * | nuc | nuc-B8-1 | 0.0 | 0.2 (3) | 0.2 | 0.4 |
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Rammensee, H.-G.; Gouttefangeas, C.; Heidu, S.; Klein, R.; Preuß, B.; Walz, J.S.; Nelde, A.; Haen, S.P.; Reth, M.; Yang, J.; Tabatabai, G.; Bösmüller, H.; Hoffmann, H.; Schindler, M.; Planz, O.; Wiesmüller, K.-H.; Löffler, M.W. Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups. Vaccines 2021, 9, 428. https://doi.org/10.3390/vaccines9050428
Rammensee H-G, Gouttefangeas C, Heidu S, Klein R, Preuß B, Walz JS, Nelde A, Haen SP, Reth M, Yang J, Tabatabai G, Bösmüller H, Hoffmann H, Schindler M, Planz O, Wiesmüller K-H, Löffler MW. Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups. Vaccines. 2021; 9(5):428. https://doi.org/10.3390/vaccines9050428
Chicago/Turabian StyleRammensee, Hans-Georg, Cécile Gouttefangeas, Sonja Heidu, Reinhild Klein, Beate Preuß, Juliane Sarah Walz, Annika Nelde, Sebastian P. Haen, Michael Reth, Jianying Yang, Ghazaleh Tabatabai, Hans Bösmüller, Helen Hoffmann, Michael Schindler, Oliver Planz, Karl-Heinz Wiesmüller, and Markus W. Löffler. 2021. "Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups" Vaccines 9, no. 5: 428. https://doi.org/10.3390/vaccines9050428