Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens
Cytotoxic T lymphocytes (CTLs) with strong abilities to suppress HIV-1 replication and recognize circulating HIV-1 could be key for both HIV-1 cure and prophylaxis. We recently designed conserved mosaic T-cell vaccine immunogens tHIVconsvX composed of 6 Gag and Pol regions. Since the tHIVconsvX vacc...
| Hoofdauteurs: | , , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
American Society for Microbiology
2019
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| _version_ | 1826291545649709056 |
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| author | Zou, C Murakoshi, H Kuse, N Akahoshi, T Chikata, T Gatanaga, H Oka, S Hanke, T Takiguchi, M |
| author_facet | Zou, C Murakoshi, H Kuse, N Akahoshi, T Chikata, T Gatanaga, H Oka, S Hanke, T Takiguchi, M |
| author_sort | Zou, C |
| collection | OXFORD |
| description | Cytotoxic T lymphocytes (CTLs) with strong abilities to suppress HIV-1 replication and recognize circulating HIV-1 could be key for both HIV-1 cure and prophylaxis. We recently designed conserved mosaic T-cell vaccine immunogens tHIVconsvX composed of 6 Gag and Pol regions. Since the tHIVconsvX vaccine targets conserved regions common to most global HIV-1 variants and employs a bi-valent mosaic design, it is expected that it could be universal if the vaccine works. Although we recently demonstrated that CTLs specific for 5 Gag epitopes in the vaccine immunogens had strong ability to suppress HIV-1 replication in vitro and in vivo, it remains unknown whether or not the Pol region-specific CTLs are equally efficient. Here, we studied CTLs specific for Pol epitopes in the immunogens in treatment-naïve Japanese patients infected with HIV-1 clade B. Overall, we mapped 20 reported and 5 novel Pol conserved epitopes in tHIVconsvX. Responses to 6 Pol epitopes were significantly associated with good clinical outcome, suggesting that CTLs specific for these 6 Pol epitopes had a strong ability to suppress HIV-1 replication in HIV-1-infected individuals. In vitro T-cell analyses further confirmed that the Pol-specific CTLs could effectively suppress HIV-1 replication. The present study thus demonstrated that the Pol regions of the vaccine contained protective epitopes. T-cell responses to the previous 5 Gag and present 6 Pol protective epitopes together also showed a strong correlation with better clinical outcome. These findings support the testing of the conserved mosaic vaccine in HIV-1 cure and prevention in humans. <br/><br/> <strong>IMPORTANCE</strong> It is likely necessary for an effective AIDS vaccine to elicit CD8+ T cells with the ability to recognize circulating HIV-1 and suppress their replication. We recently developed novel bivalent-mosaic T-cell vaccine immunogens composed of conserved regions of the Gag and Pol proteins match to at least 80% globally circulating HIV-1 isolates. Nevertheless, it remains to be proven if vaccine with these immunogens can elicit T cells with the ability to suppress HIV-1 replication. It is well known that Gag-specific T cells can suppress HIV-1 replication more effectively than T cells specific for epitopes in other proteins. We recently identified 5 protective Gag epitopes in the vaccine immunogens. We here identified T cells specific for 6 Pol epitopes present in the immunogens with strong abilities to suppress HIV-1 in vivo and in vitro. This study further encourages clinical testing of the conserved mosaic T-cell vaccine in HIV-1 prevention and cure. |
| first_indexed | 2024-03-07T03:01:00Z |
| format | Journal article |
| id | oxford-uuid:b0f5d766-266b-4d24-94fe-854357e16df5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:01:00Z |
| publishDate | 2019 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:b0f5d766-266b-4d24-94fe-854357e16df52022-03-27T04:00:21ZEffective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogensJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0f5d766-266b-4d24-94fe-854357e16df5EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2019Zou, CMurakoshi, HKuse, NAkahoshi, TChikata, TGatanaga, HOka, SHanke, TTakiguchi, MCytotoxic T lymphocytes (CTLs) with strong abilities to suppress HIV-1 replication and recognize circulating HIV-1 could be key for both HIV-1 cure and prophylaxis. We recently designed conserved mosaic T-cell vaccine immunogens tHIVconsvX composed of 6 Gag and Pol regions. Since the tHIVconsvX vaccine targets conserved regions common to most global HIV-1 variants and employs a bi-valent mosaic design, it is expected that it could be universal if the vaccine works. Although we recently demonstrated that CTLs specific for 5 Gag epitopes in the vaccine immunogens had strong ability to suppress HIV-1 replication in vitro and in vivo, it remains unknown whether or not the Pol region-specific CTLs are equally efficient. Here, we studied CTLs specific for Pol epitopes in the immunogens in treatment-naïve Japanese patients infected with HIV-1 clade B. Overall, we mapped 20 reported and 5 novel Pol conserved epitopes in tHIVconsvX. Responses to 6 Pol epitopes were significantly associated with good clinical outcome, suggesting that CTLs specific for these 6 Pol epitopes had a strong ability to suppress HIV-1 replication in HIV-1-infected individuals. In vitro T-cell analyses further confirmed that the Pol-specific CTLs could effectively suppress HIV-1 replication. The present study thus demonstrated that the Pol regions of the vaccine contained protective epitopes. T-cell responses to the previous 5 Gag and present 6 Pol protective epitopes together also showed a strong correlation with better clinical outcome. These findings support the testing of the conserved mosaic vaccine in HIV-1 cure and prevention in humans. <br/><br/> <strong>IMPORTANCE</strong> It is likely necessary for an effective AIDS vaccine to elicit CD8+ T cells with the ability to recognize circulating HIV-1 and suppress their replication. We recently developed novel bivalent-mosaic T-cell vaccine immunogens composed of conserved regions of the Gag and Pol proteins match to at least 80% globally circulating HIV-1 isolates. Nevertheless, it remains to be proven if vaccine with these immunogens can elicit T cells with the ability to suppress HIV-1 replication. It is well known that Gag-specific T cells can suppress HIV-1 replication more effectively than T cells specific for epitopes in other proteins. We recently identified 5 protective Gag epitopes in the vaccine immunogens. We here identified T cells specific for 6 Pol epitopes present in the immunogens with strong abilities to suppress HIV-1 in vivo and in vitro. This study further encourages clinical testing of the conserved mosaic T-cell vaccine in HIV-1 prevention and cure. |
| spellingShingle | Zou, C Murakoshi, H Kuse, N Akahoshi, T Chikata, T Gatanaga, H Oka, S Hanke, T Takiguchi, M Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title | Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title_full | Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title_fullStr | Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title_full_unstemmed | Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title_short | Effective suppression of HIV-1 replication by cytotoxic T lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
| title_sort | effective suppression of hiv 1 replication by cytotoxic t lymphocytes specific for pol epitopes in conserved mosaic vaccine immunogens |
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