Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses
The efficacy of anti-viral T-cell vaccines may greatly depend on their ability to generate high-magnitude responses targeting a broad range of different epitopes. Recently, we created the HIV T-cell immunogen HTI, designed to generate T-cell responses to protein fragments more frequently targeted by...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/3/279 |
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| author | Alex Olvera Luis Romero-Martin Bruna Oriol-Tordera Miriam Rosas-Umbert Tuixent Escribà Beatriz Mothe Christian Brander |
| author_facet | Alex Olvera Luis Romero-Martin Bruna Oriol-Tordera Miriam Rosas-Umbert Tuixent Escribà Beatriz Mothe Christian Brander |
| author_sort | Alex Olvera |
| collection | DOAJ |
| description | The efficacy of anti-viral T-cell vaccines may greatly depend on their ability to generate high-magnitude responses targeting a broad range of different epitopes. Recently, we created the HIV T-cell immunogen HTI, designed to generate T-cell responses to protein fragments more frequently targeted by HIV controllers. In the present study, we aim to maximize the breadth and magnitude of the T-cell responses generated by HTI by combining different vaccine vectors expressing HTI. We evaluated the ability to induce strong and broad T-cell responses to the HTI immunogen through prime vaccination with DNA plasmid (D) or Chimpanzee Adenovirus Ox1 (ChAdOx1; C) vectors, followed by a Modified Virus Ankara (MVA; M) vaccine boost (DDD, DDDM, C, and CM). HTI-specific T-cell responses after vaccination were measured by IFN-γ-ELISpot assays in two inbred mice strains (C57BL/6 and BALB/c). CM was the schedule triggering the highest magnitude of the response in both mice strains. However, this effect was not reflected in an increase in the breadth of the response but rather in an increase in the magnitude of the response to specific immunodominant epitopes. Immunodominance profiles in the two mouse strains were different, with a clear dominance of T-cell responses to a Pol-derived peptide pool after CM vaccination in C57BL/6. Responses to CM vaccination were also maintained at higher magnitudes over time (13 weeks) compared to other vaccination regimens. Thus, while a ChAdOx1 prime combined with MVA booster vaccination generated stronger and more sustained T-cell responses compared to three DNA vaccinations, the ChAdOx1 primed responses were more narrowly targeted. In conclusion, our findings suggest that the choice of vaccine vectors and prime-boost regimens plays a crucial role in determining the strength, duration, breadth, and focus of T-cell responses, providing further guidance for selecting vaccination strategies. |
| first_indexed | 2024-04-24T17:45:55Z |
| format | Article |
| id | doaj.art-3e38dbd850c44131bf763791e9e2d017 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-24T17:45:55Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-3e38dbd850c44131bf763791e9e2d0172024-03-27T14:07:01ZengMDPI AGVaccines2076-393X2024-03-0112327910.3390/vaccines12030279Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell ResponsesAlex Olvera0Luis Romero-Martin1Bruna Oriol-Tordera2Miriam Rosas-Umbert3Tuixent Escribà4Beatriz Mothe5Christian Brander6Irsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainIrsicaixa—AIDS Research Institute, 08916 Badalona, Barcelona, SpainThe efficacy of anti-viral T-cell vaccines may greatly depend on their ability to generate high-magnitude responses targeting a broad range of different epitopes. Recently, we created the HIV T-cell immunogen HTI, designed to generate T-cell responses to protein fragments more frequently targeted by HIV controllers. In the present study, we aim to maximize the breadth and magnitude of the T-cell responses generated by HTI by combining different vaccine vectors expressing HTI. We evaluated the ability to induce strong and broad T-cell responses to the HTI immunogen through prime vaccination with DNA plasmid (D) or Chimpanzee Adenovirus Ox1 (ChAdOx1; C) vectors, followed by a Modified Virus Ankara (MVA; M) vaccine boost (DDD, DDDM, C, and CM). HTI-specific T-cell responses after vaccination were measured by IFN-γ-ELISpot assays in two inbred mice strains (C57BL/6 and BALB/c). CM was the schedule triggering the highest magnitude of the response in both mice strains. However, this effect was not reflected in an increase in the breadth of the response but rather in an increase in the magnitude of the response to specific immunodominant epitopes. Immunodominance profiles in the two mouse strains were different, with a clear dominance of T-cell responses to a Pol-derived peptide pool after CM vaccination in C57BL/6. Responses to CM vaccination were also maintained at higher magnitudes over time (13 weeks) compared to other vaccination regimens. Thus, while a ChAdOx1 prime combined with MVA booster vaccination generated stronger and more sustained T-cell responses compared to three DNA vaccinations, the ChAdOx1 primed responses were more narrowly targeted. In conclusion, our findings suggest that the choice of vaccine vectors and prime-boost regimens plays a crucial role in determining the strength, duration, breadth, and focus of T-cell responses, providing further guidance for selecting vaccination strategies.https://www.mdpi.com/2076-393X/12/3/279T-cell vaccineHIVimmunodominanceimmune memory |
| spellingShingle | Alex Olvera Luis Romero-Martin Bruna Oriol-Tordera Miriam Rosas-Umbert Tuixent Escribà Beatriz Mothe Christian Brander Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses Vaccines T-cell vaccine HIV immunodominance immune memory |
| title | Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses |
| title_full | Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses |
| title_fullStr | Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses |
| title_full_unstemmed | Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses |
| title_short | Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses |
| title_sort | impact of chadox1 or dna prime vaccination on magnitude breadth and focus of mva boosted immunogen specific t cell responses |
| topic | T-cell vaccine HIV immunodominance immune memory |
| url | https://www.mdpi.com/2076-393X/12/3/279 |
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