Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine
BackgroundHIV remains a major public health issue in spite of antiretroviral therapy (ART). An innovative vaccine that can induce long-lasting and effective immunity is required to curb the persistently high numbers of new infections worldwide.MethodsA novel DNA vaccine was generated using a Simian-...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481427/full |
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| author | Deepanwita Bose Kenneth A. Rogers Lisa M. Shirreff Yahia Chebloune Francois J. Villinger |
| author_facet | Deepanwita Bose Kenneth A. Rogers Lisa M. Shirreff Yahia Chebloune Francois J. Villinger |
| author_sort | Deepanwita Bose |
| collection | DOAJ |
| description | BackgroundHIV remains a major public health issue in spite of antiretroviral therapy (ART). An innovative vaccine that can induce long-lasting and effective immunity is required to curb the persistently high numbers of new infections worldwide.MethodsA novel DNA vaccine was generated using a Simian-Human Immunodeficiency Virus (SHIV) backbone with a Zambian T/F clade C envelope and under the control of the caprine arthritis encephalitis virus long terminal repeats (LTRs) for constitutive expression. Due to the deleted integrase, this DNA vaccine “CSH-DIN-T/F Z331” performs only a single replication cycle. To increase immunogenicity, the co-expression of apoptotic genes (BAX, BAK, or caspase 8) incorporated at the end of Pol was tested to promote the release of apoptotic bodies taken up by dendritic cells leading to cross-presentation of antigen. The three vaccines (CSH-DIN-T/F Z331-BAX, CSH-DIN-T/F Z331-BAK, and CSH-DIN-T/F Z331-Cas8) were tested in vitro for expression and in vivo in BALB/cJ mice for immunogenicity.ResultsTransduced HEK293 cells co-cultured with CEMx174 confirmed the single replication cycle of the DNA vaccine and the induction of apoptosis by CSH-DIN-T/F Z331-Cas8 based on Annexin V expression. BALB/cJ mice were immunized with a combined intramuscular + intradermal/electroporation approach. Intracellular cytokine staining (ICS) from splenocytes collected 12 weeks post-prime/6 weeks post-boost demonstrated a clear superiority of caspase 8 expressing construct over the others, with higher proportions of IFN-γ-, IL-2-, and IL-21-producing CD8 T cells specific to Env, Gag, and Nef. The kinetics of immune response after various immunization schedules were also investigated.ConclusionThis novel single-cycle DNA vaccine with apoptotic genes demonstrated an enhanced immunogenicity primarily for antigen-specific CD8+ T-cell responses. |
| format | Article |
| id | doaj-art-b282b2cfaaab4c9dbfdd00bd71abf4ff |
| institution | DOAJ |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-b282b2cfaaab4c9dbfdd00bd71abf4ff2025-08-20T03:08:43ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-04-011510.3389/fcimb.2025.14814271481427Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccineDeepanwita Bose0Kenneth A. Rogers1Lisa M. Shirreff2Yahia Chebloune3Francois J. Villinger4New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesLaboratoire Pathogénèse et Vaccination Lentivirales (PAVAL) Lab., Institut National de Recherche d’Agriculture et Environnement, Université Grenoble Alpes, Saint Martin d’Hères, FranceNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesBackgroundHIV remains a major public health issue in spite of antiretroviral therapy (ART). An innovative vaccine that can induce long-lasting and effective immunity is required to curb the persistently high numbers of new infections worldwide.MethodsA novel DNA vaccine was generated using a Simian-Human Immunodeficiency Virus (SHIV) backbone with a Zambian T/F clade C envelope and under the control of the caprine arthritis encephalitis virus long terminal repeats (LTRs) for constitutive expression. Due to the deleted integrase, this DNA vaccine “CSH-DIN-T/F Z331” performs only a single replication cycle. To increase immunogenicity, the co-expression of apoptotic genes (BAX, BAK, or caspase 8) incorporated at the end of Pol was tested to promote the release of apoptotic bodies taken up by dendritic cells leading to cross-presentation of antigen. The three vaccines (CSH-DIN-T/F Z331-BAX, CSH-DIN-T/F Z331-BAK, and CSH-DIN-T/F Z331-Cas8) were tested in vitro for expression and in vivo in BALB/cJ mice for immunogenicity.ResultsTransduced HEK293 cells co-cultured with CEMx174 confirmed the single replication cycle of the DNA vaccine and the induction of apoptosis by CSH-DIN-T/F Z331-Cas8 based on Annexin V expression. BALB/cJ mice were immunized with a combined intramuscular + intradermal/electroporation approach. Intracellular cytokine staining (ICS) from splenocytes collected 12 weeks post-prime/6 weeks post-boost demonstrated a clear superiority of caspase 8 expressing construct over the others, with higher proportions of IFN-γ-, IL-2-, and IL-21-producing CD8 T cells specific to Env, Gag, and Nef. The kinetics of immune response after various immunization schedules were also investigated.ConclusionThis novel single-cycle DNA vaccine with apoptotic genes demonstrated an enhanced immunogenicity primarily for antigen-specific CD8+ T-cell responses.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481427/fullSHIVDNA vaccinelentivectorapoptotic geneimmune responsesmouse immunization |
| spellingShingle | Deepanwita Bose Kenneth A. Rogers Lisa M. Shirreff Yahia Chebloune Francois J. Villinger Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine Frontiers in Cellular and Infection Microbiology SHIV DNA vaccine lentivector apoptotic gene immune responses mouse immunization |
| title | Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine |
| title_full | Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine |
| title_fullStr | Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine |
| title_full_unstemmed | Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine |
| title_short | Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine |
| title_sort | enhanced hiv immune responses elicited by an apoptotic single cycle shiv lentivector dna vaccine |
| topic | SHIV DNA vaccine lentivector apoptotic gene immune responses mouse immunization |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481427/full |
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