CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication
Abstract Background Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-spec...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12977-018-0429-y |
| _version_ | 1819160310318104576 |
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| author | Hayato Murakoshi Chengcheng Zou Nozomi Kuse Tomohiro Akahoshi Takayuki Chikata Hiroyuki Gatanaga Shinichi Oka Tomáš Hanke Masafumi Takiguchi |
| author_facet | Hayato Murakoshi Chengcheng Zou Nozomi Kuse Tomohiro Akahoshi Takayuki Chikata Hiroyuki Gatanaga Shinichi Oka Tomáš Hanke Masafumi Takiguchi |
| author_sort | Hayato Murakoshi |
| collection | DOAJ |
| description | Abstract Background Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. We recently designed T-cell mosaic vaccine immunogens tHIVconsvX composed of 6 conserved Gag and Pol regions and demonstrated that the T-cell responses to peptides derived from the vaccine immunogens were significantly associated with lower plasma viral load (pVL) and higher CD4+ T-cell count (CD4 count) in HIV-1-infected, treatment-naive Japanese individuals. However, it remains unknown T cells of which specificities have the ability to suppress HIV-1 replication. In the present study, we sought to identify more T cells specific for protective Gag epitopes in the vaccine immunogens, and analyze their abilities to suppress HIV-1 replication and recognize epitope variants in circulating HIV-1. Results We determined 17 optimal Gag epitopes and their HLA restriction, and found that T-cell responses to 9 were associated significantly with lower pVL and/or higher CD4 count. T-cells recognizing 5 of these Gag peptides remained associated with good clinical outcome in 221 HIV-1-infected individuals even when comparing responders and non-responders with the same restricting HLA alleles. Although it was known previously that T cells specific for 3 of these protective epitopes had strong abilities to suppress HIV-1 replication in vivo, here we demonstrated equivalent abilities for the 2 novel epitopes. Furthermore, T cells against all 5 Gag epitopes cross-recognized variants in majority of circulating HIV-1. Conclusions We demonstrated that T cells specific for 5 Gag conserved epitopes in the tHIVconsvX have ability to suppress replication of circulating HIV-1 in HIV-1-infected individuals. Therefore, the tHIVconsvX vaccines have the right specificity to contribute to prevention of HIV-1 infection and eradication of latently infected cells following HIV-1 reactivation. |
| first_indexed | 2024-12-22T16:54:25Z |
| format | Article |
| id | doaj.art-88f6db15ff354ba384804dfa920b05d9 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-22T16:54:25Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-88f6db15ff354ba384804dfa920b05d92022-12-21T18:19:30ZengBMCRetrovirology1742-46902018-07-0115111410.1186/s12977-018-0429-yCD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replicationHayato Murakoshi0Chengcheng Zou1Nozomi Kuse2Tomohiro Akahoshi3Takayuki Chikata4Hiroyuki Gatanaga5Shinichi Oka6Tomáš Hanke7Masafumi Takiguchi8Center for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityInternational Research Center of Medical Sciences, Kumamoto UniversityCenter for AIDS Research, Kumamoto UniversityAbstract Background Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. We recently designed T-cell mosaic vaccine immunogens tHIVconsvX composed of 6 conserved Gag and Pol regions and demonstrated that the T-cell responses to peptides derived from the vaccine immunogens were significantly associated with lower plasma viral load (pVL) and higher CD4+ T-cell count (CD4 count) in HIV-1-infected, treatment-naive Japanese individuals. However, it remains unknown T cells of which specificities have the ability to suppress HIV-1 replication. In the present study, we sought to identify more T cells specific for protective Gag epitopes in the vaccine immunogens, and analyze their abilities to suppress HIV-1 replication and recognize epitope variants in circulating HIV-1. Results We determined 17 optimal Gag epitopes and their HLA restriction, and found that T-cell responses to 9 were associated significantly with lower pVL and/or higher CD4 count. T-cells recognizing 5 of these Gag peptides remained associated with good clinical outcome in 221 HIV-1-infected individuals even when comparing responders and non-responders with the same restricting HLA alleles. Although it was known previously that T cells specific for 3 of these protective epitopes had strong abilities to suppress HIV-1 replication in vivo, here we demonstrated equivalent abilities for the 2 novel epitopes. Furthermore, T cells against all 5 Gag epitopes cross-recognized variants in majority of circulating HIV-1. Conclusions We demonstrated that T cells specific for 5 Gag conserved epitopes in the tHIVconsvX have ability to suppress replication of circulating HIV-1 in HIV-1-infected individuals. Therefore, the tHIVconsvX vaccines have the right specificity to contribute to prevention of HIV-1 infection and eradication of latently infected cells following HIV-1 reactivation.http://link.springer.com/article/10.1186/s12977-018-0429-yHIV-1GagCTLVaccineConserved epitope |
| spellingShingle | Hayato Murakoshi Chengcheng Zou Nozomi Kuse Tomohiro Akahoshi Takayuki Chikata Hiroyuki Gatanaga Shinichi Oka Tomáš Hanke Masafumi Takiguchi CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication Retrovirology HIV-1 Gag CTL Vaccine Conserved epitope |
| title | CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication |
| title_full | CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication |
| title_fullStr | CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication |
| title_full_unstemmed | CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication |
| title_short | CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication |
| title_sort | cd8 t cells specific for conserved cross reactive gag epitopes with strong ability to suppress hiv 1 replication |
| topic | HIV-1 Gag CTL Vaccine Conserved epitope |
| url | http://link.springer.com/article/10.1186/s12977-018-0429-y |
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