Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex
Human herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalit...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/4697529 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849304935565361152 |
|---|---|
| author | Mie Okutani Akiko Kawabata Mitsuhiro Nishimura Satoshi Nagamata Soichiro Kuwabara Yasunari Haseda Lisa Munakata Ryo Suzuki Yasuko Mori Taiki Aoshi |
| author_facet | Mie Okutani Akiko Kawabata Mitsuhiro Nishimura Satoshi Nagamata Soichiro Kuwabara Yasunari Haseda Lisa Munakata Ryo Suzuki Yasuko Mori Taiki Aoshi |
| author_sort | Mie Okutani |
| collection | DOAJ |
| description | Human herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalitis/encephalopathy, and half of the patients developed encephalopathy reported to have neurological sequelae. Furthermore, after primary infection, HHV-6B remains in a latent state and sometimes reactivated in immunosuppressed patients, causing life-threatening severe encephalopathy. However, effective immunotherapies or vaccines for controlling HHV-6B infection and reactivation have not yet been established. Recently, we have found that the HHV-6B tetrameric glycoprotein (g) complex, gH/gL/gQ1/gQ2 is a promising vaccine candidate, and currently under preclinical development. To confirm our vaccine candidate protein complex induce detectable T-cell responses, in this study, we comprehensively screened CD4+ and CD8+ T-cell epitopes in the gH/gL/gQ1/gQ2 tetrameric complex protein in mice immunisation model. Both BALB/c and C57BL/6 mice were immunised with the tetrameric complex protein or plasmid DNA encoding gH, gL, gQ1, and gQ2, and then restimulated with 162 20-mer peptides covering the whole gH/gL/gQ1/gQ2 sequences; multiple CD4+ and CD8+ T-cell-stimulating peptides were identified in both BALB/c and C57BL/6 mice. Our study demonstrates that gH/gL/gQ1/gQ2 tetramer-targeted vaccination has potential to induce T-cell responses in two different strains of mice and supports the future development and application of T-cell-inducing vaccine and immunotherapies against HHV-6B. |
| format | Article |
| id | doaj-art-3b1eb111a9d443dd9e7906406644d2a5 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-3b1eb111a9d443dd9e7906406644d2a52025-08-20T03:55:36ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/46975294697529Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer ComplexMie Okutani0Akiko Kawabata1Mitsuhiro Nishimura2Satoshi Nagamata3Soichiro Kuwabara4Yasunari Haseda5Lisa Munakata6Ryo Suzuki7Yasuko Mori8Taiki Aoshi9BIKEN Center for Innovative Vaccine Research and Development, The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, JapanBIKEN Center for Innovative Vaccine Research and Development, The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, JapanVaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, JapanLaboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, JapanLaboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, JapanVaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, JapanHuman herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalitis/encephalopathy, and half of the patients developed encephalopathy reported to have neurological sequelae. Furthermore, after primary infection, HHV-6B remains in a latent state and sometimes reactivated in immunosuppressed patients, causing life-threatening severe encephalopathy. However, effective immunotherapies or vaccines for controlling HHV-6B infection and reactivation have not yet been established. Recently, we have found that the HHV-6B tetrameric glycoprotein (g) complex, gH/gL/gQ1/gQ2 is a promising vaccine candidate, and currently under preclinical development. To confirm our vaccine candidate protein complex induce detectable T-cell responses, in this study, we comprehensively screened CD4+ and CD8+ T-cell epitopes in the gH/gL/gQ1/gQ2 tetrameric complex protein in mice immunisation model. Both BALB/c and C57BL/6 mice were immunised with the tetrameric complex protein or plasmid DNA encoding gH, gL, gQ1, and gQ2, and then restimulated with 162 20-mer peptides covering the whole gH/gL/gQ1/gQ2 sequences; multiple CD4+ and CD8+ T-cell-stimulating peptides were identified in both BALB/c and C57BL/6 mice. Our study demonstrates that gH/gL/gQ1/gQ2 tetramer-targeted vaccination has potential to induce T-cell responses in two different strains of mice and supports the future development and application of T-cell-inducing vaccine and immunotherapies against HHV-6B.http://dx.doi.org/10.1155/2020/4697529 |
| spellingShingle | Mie Okutani Akiko Kawabata Mitsuhiro Nishimura Satoshi Nagamata Soichiro Kuwabara Yasunari Haseda Lisa Munakata Ryo Suzuki Yasuko Mori Taiki Aoshi Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex Journal of Immunology Research |
| title | Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex |
| title_full | Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex |
| title_fullStr | Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex |
| title_full_unstemmed | Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex |
| title_short | Comprehensive Screening of Mouse T-Cell Epitopes in Human Herpesvirus 6B Glycoprotein H/L/Q1/Q2 Tetramer Complex |
| title_sort | comprehensive screening of mouse t cell epitopes in human herpesvirus 6b glycoprotein h l q1 q2 tetramer complex |
| url | http://dx.doi.org/10.1155/2020/4697529 |
| work_keys_str_mv | AT mieokutani comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT akikokawabata comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT mitsuhironishimura comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT satoshinagamata comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT soichirokuwabara comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT yasunarihaseda comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT lisamunakata comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT ryosuzuki comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT yasukomori comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex AT taikiaoshi comprehensivescreeningofmousetcellepitopesinhumanherpesvirus6bglycoproteinhlq1q2tetramercomplex |