Olvera Alex, Romero-Martin Luis, Oriol-Tordera Bruna, Rosas-Umbert Miriam, Escribà Tuixent, Mothe Beatriz, Brander Christian
Irsicaixa-AIDS Research Institute, 08916 Badalona, Barcelona, Spain.
Faculty of Sciences and Technology, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Barcelona, Spain.
Vaccines (Basel). 2024 Mar 7;12(3):279. doi: 10.3390/vaccines12030279.
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.
抗病毒T细胞疫苗的疗效可能在很大程度上取决于其产生针对广泛不同表位的高强度反应的能力。最近，我们构建了HIV T细胞免疫原HTI，旨在产生针对HIV控制者更频繁靶向的蛋白质片段的T细胞反应。在本研究中，我们旨在通过组合表达HTI的不同疫苗载体，最大化HTI产生的T细胞反应的广度和强度。我们评估了通过用DNA质粒（D）或黑猩猩腺病毒Ox1（ChAdOx1；C）载体进行初次接种，随后用改良安卡拉病毒（MVA；M）疫苗加强免疫（DDD、DDDM、C和CM）来诱导对HTI免疫原产生强烈且广泛的T细胞反应的能力。在两种近交小鼠品系（C57BL/6和BALB/c）中，通过IFN-γ-ELISpot试验测量接种疫苗后的HTI特异性T细胞反应。CM方案在两种小鼠品系中均引发了最高强度的反应。然而，这种效应并未体现在反应广度的增加上，而是体现在对特定免疫显性表位的反应强度的增加上。两种小鼠品系中的免疫显性谱不同，在C57BL/6中，CM接种后对Pol衍生肽库的T细胞反应明显占主导。与其他接种方案相比，对CM接种的反应在较长时间（13周）内也维持在较高强度。因此，虽然与三次DNA接种相比，ChAdOx1初次接种联合MVA加强免疫产生了更强且更持久的T细胞反应，但ChAdOx1初次接种引发的反应靶向性更窄。总之，我们的研究结果表明，疫苗载体和初免-加强方案的选择在决定T细胞反应的强度、持续时间、广度和靶向性方面起着关键作用，为选择接种策略提供了进一步的指导。
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