Priming with Recombinant BCG Expressing HTI Enhances the Magnitude and Breadth of the T-Cell Immune Responses Elicited by MVA.HTI in BALB/c Mice

Saubí, Narcís; Kilpeläinen, Athina; Eto, Yoshiki; Chen, Chun-Wei; Olvera, Àlex; Hanke, Tomáš; Berthou, Christian; Joseph-Munné, Joan

doi:10.3390/vaccines8040678

Cited by 4 publications

(7 citation statements)

References 39 publications

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“…3 out of 8 mice (~38%) elicited the highest L1-specific IFN-γ responses ( Figure 7 B). This might be attributed to the unspecific adjuvanticity of BCG according our previous studies [ 64 , 65 , 66 ]. The evident priming effect, even by wild-type BCG, is in line with the ability of rBCG derivatives to act as potent adjuvants for subsequent boosting vaccines [ 64 , 65 ].…”

Section: Resultsmentioning

confidence: 88%

“…The 2nd-generation HIVconsvX immunogens were designed by redefining the group M conserved regions and utilizes a bivalent mosaic design to maximize the match of potential 9-mer T-cell epitopes in the vaccine to global variants [ 64 ]. The HTI immunogen was designed to cover T-cell targets against which T-cell responses are predominantly observed in HIV-1-infected individuals with low HIV-1 viral loads [ 65 , 66 ]. Because papilloma VLPs have been proved to be a multiple CTL epitope carrier [ 17 ], we aimed to construct chimeric HPV16 L1 VLPs carrying multiple conserved HIV-1 CTL epitopes in combination with rBCG expressing ThivconsvX or HTI T-cell immunogens to induce broader CTL immune responses against HIV-1.…”

Section: Discussionmentioning

confidence: 99%

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Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice

et al. 2022

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In this study, the HIV-1 P18I10 CTL peptide derived from the V3 loop of HIV-1 gp120 and the T20 anti-fusion peptide of HIV-1 gp41 were inserted into the HPV16 L1 capsid protein to construct chimeric HPV:HIV (L1:P18I10 and L1:T20) VLPs by using the mammalian cell expression system. The HPV:HIV VLPs were purified by chromatography. We demonstrated that the insertion of P18I10 or T20 peptides into the DE loop of HPV16 L1 capsid proteins did not affect in vitro stability, self-assembly and morphology of chimeric HPV:HIV VLPs. Importantly, it did not interfere either with the HIV-1 antibody reactivity targeting sequential and conformational P18I10 and T20 peptides presented on chimeric HPV:HIV VLPs or with the induction of HPV16 L1-specific antibodies in vivo. We observed that chimeric L1:P18I10/L1:T20 VLPs vaccines could induce HPV16- but weak HIV-1-specific antibody responses and elicited HPV16- and HIV-1-specific T-cell responses in BALB/c mice. Moreover, could be a potential booster to increase HIV-specific cellular responses in the heterologous immunization after priming with rBCG.HIVA vaccine. This research work would contribute a step towards the development of the novel chimeric HPV:HIV VLP-based vaccine platform for controlling HPV16 and HIV-1 infection, which is urgently needed in developing and industrialized countries.

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Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice

et al. 2022

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“…Based on these regions, we designed the HIV T-cell Immunogen (HTI) to target T-cell responses to HIV proteome fragments vulnerable to T-cell immunity, avoiding responses to decoy epitopes [ 56 ]. HTI has been shown to be immunogenic in mice and non-human primates [ 56 , 58 , 59 ] when using different vaccine vectors such as DNA plasmids, Chimpanzee Adenovirus (ChAdOx1), Modified Vaccinia virus Ankara (MVA), or Bacillus Calmette–Guérin (BCG), and has been successfully tested in human clinical trials of therapeutic HIV vaccination [ 60 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses

Olvera,

Romero-Martin,

Oriol-Tordera

et al. 2024

Vaccines

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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.

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“…The HTI open reading frame (ORF) has been inserted into different vaccine vectors [62], including DNA plasmid, the Chimpanzee Adenovirus, and modified Vaccinia Ankara vaccine vectors. These HTI-expressing vectors have been tested in different prime-boost strategies in mice [62,[64][65][66][67][68], non-human primates [62], and humans [69,70], showing strong immunogenicity in all cases.…”

Section: Introductionmentioning

confidence: 99%

Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels

Elizalde-Torrent,

Borgognone,

Casadellà

et al. 2023

Vaccines

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Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.

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Priming with Recombinant BCG Expressing HTI Enhances the Magnitude and Breadth of the T-Cell Immune Responses Elicited by MVA.HTI in BALB/c Mice

Cited by 4 publications

References 39 publications

Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice

Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice

Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses

Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels

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