Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus
A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) vaccine able to induce long-lasting immunity remains a major challenge. We previously designed a T cell multiepitopic immunogen including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (TMEP-B), that...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/3/57 |
| _version_ | 1811185204333641728 |
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| author | Beatriz Perdiguero Cristina Sánchez-Corzo Carlos Oscar S. Sorzano Pilar Mediavilla Lidia Saiz Mariano Esteban Carmen Elena Gómez |
| author_facet | Beatriz Perdiguero Cristina Sánchez-Corzo Carlos Oscar S. Sorzano Pilar Mediavilla Lidia Saiz Mariano Esteban Carmen Elena Gómez |
| author_sort | Beatriz Perdiguero |
| collection | DOAJ |
| description | A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) vaccine able to induce long-lasting immunity remains a major challenge. We previously designed a T cell multiepitopic immunogen including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (TMEP-B), that induced potent HIV-1-specific CD8 T cells when vectored by DNA and combined with the vaccine candidate modified vaccinia virus Ankara (MVA)-B. Here, we described the vectorization of TMEP-B in MVA (MVA-TMEP) and evaluated the T cell immunogenicity profile elicited in mice when administered in homologous (MVA/MVA) or heterologous (DNA/MVA) prime/boost vector regimens or using homologous or heterologous inserts. The heterologous vector regimen was superior to the homologous protocol in inducing T cell responses. DNA-TMEP-primed animals boosted with MVA-TMEP or MVA-B exhibited the highest magnitudes of HIV-1-specific CD8, CD4 and T follicular helper (Tfh) cells, with MVA-TMEP significantly expanding Gag-specific CD8 T cell responses. In the homologous vector regimen, all groups exhibited similar HIV-1-specific CD8 and CD4 T cell responses, but both MVA-B/MVA-B and MVA-TMEP/MVA-TMEP combinations elicited higher Gag-Pol-Nef (GPN)-specific CD8 T cell responses compared to MVA-TMEP/MVA-B. Our results revealed an enhanced induction of HIV-1-specific T cell responses by TMEP-B when vectored in both DNA and MVA, and supported their use in combined prime/boost strategies for HIV-1 prevention and/or therapy. |
| first_indexed | 2024-04-11T13:25:26Z |
| format | Article |
| id | doaj.art-34ba30fc7e86492faf0846639fcfe28d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T13:25:26Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-34ba30fc7e86492faf0846639fcfe28d2022-12-22T04:22:05ZengMDPI AGVaccines2076-393X2019-06-01735710.3390/vaccines7030057vaccines7030057Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA VirusBeatriz Perdiguero0Cristina Sánchez-Corzo1Carlos Oscar S. Sorzano2Pilar Mediavilla3Lidia Saiz4Mariano Esteban5Carmen Elena Gómez6Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainBiocomputing Unit, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, SpainA human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) vaccine able to induce long-lasting immunity remains a major challenge. We previously designed a T cell multiepitopic immunogen including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (TMEP-B), that induced potent HIV-1-specific CD8 T cells when vectored by DNA and combined with the vaccine candidate modified vaccinia virus Ankara (MVA)-B. Here, we described the vectorization of TMEP-B in MVA (MVA-TMEP) and evaluated the T cell immunogenicity profile elicited in mice when administered in homologous (MVA/MVA) or heterologous (DNA/MVA) prime/boost vector regimens or using homologous or heterologous inserts. The heterologous vector regimen was superior to the homologous protocol in inducing T cell responses. DNA-TMEP-primed animals boosted with MVA-TMEP or MVA-B exhibited the highest magnitudes of HIV-1-specific CD8, CD4 and T follicular helper (Tfh) cells, with MVA-TMEP significantly expanding Gag-specific CD8 T cell responses. In the homologous vector regimen, all groups exhibited similar HIV-1-specific CD8 and CD4 T cell responses, but both MVA-B/MVA-B and MVA-TMEP/MVA-TMEP combinations elicited higher Gag-Pol-Nef (GPN)-specific CD8 T cell responses compared to MVA-TMEP/MVA-B. Our results revealed an enhanced induction of HIV-1-specific T cell responses by TMEP-B when vectored in both DNA and MVA, and supported their use in combined prime/boost strategies for HIV-1 prevention and/or therapy.https://www.mdpi.com/2076-393X/7/3/57HIV-1 vaccineMVA vectorT cell multiepitopesimmunogenicity in miceT cell responses |
| spellingShingle | Beatriz Perdiguero Cristina Sánchez-Corzo Carlos Oscar S. Sorzano Pilar Mediavilla Lidia Saiz Mariano Esteban Carmen Elena Gómez Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus Vaccines HIV-1 vaccine MVA vector T cell multiepitopes immunogenicity in mice T cell responses |
| title | Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus |
| title_full | Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus |
| title_fullStr | Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus |
| title_full_unstemmed | Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus |
| title_short | Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus |
| title_sort | induction of broad and polyfunctional hiv 1 specific t cell responses by the multiepitopic protein tmep b vectored by mva virus |
| topic | HIV-1 vaccine MVA vector T cell multiepitopes immunogenicity in mice T cell responses |
| url | https://www.mdpi.com/2076-393X/7/3/57 |
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