Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate.
Flaviviruses represent a significant global health threat and relatively few licensed vaccines exist to protect against them. Insect-specific flaviviruses (ISFVs) are incapable of replication in humans and have emerged as a novel and promising tool for flavivirus vaccine development. ISFV-based flav...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012566 |
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| author | Danielle L Porier Awadalkareem Adam Lin Kang Pawel Michalak Juselyn Tupik Matthew A Santos Manette Tanelus Krisangel López Dawn I Auguste Christy Lee Irving C Allen Tian Wang Albert J Auguste |
| author_facet | Danielle L Porier Awadalkareem Adam Lin Kang Pawel Michalak Juselyn Tupik Matthew A Santos Manette Tanelus Krisangel López Dawn I Auguste Christy Lee Irving C Allen Tian Wang Albert J Auguste |
| author_sort | Danielle L Porier |
| collection | DOAJ |
| description | Flaviviruses represent a significant global health threat and relatively few licensed vaccines exist to protect against them. Insect-specific flaviviruses (ISFVs) are incapable of replication in humans and have emerged as a novel and promising tool for flavivirus vaccine development. ISFV-based flavivirus vaccines have shown exceptional safety, immunogenicity, and efficacy, however, a detailed assessment of the correlates of protection and immune responses induced by these vaccines are still needed for vaccine optimization. Here, we explore the mechanisms of protective immunity induced by a previously created pre-clinical Zika virus (ZIKV) vaccine candidate, called Aripo/Zika (ARPV/ZIKV). In brief, immunocompromised IFN-αβR-/- mice passively immunized with ARPV/ZIKV immune sera experienced protection after lethal ZIKV challenge, although this protection was incomplete. ARPV/ZIKV-vaccinated IFN-αβR-/- mice depleted of CD4+ or CD8+ T-cells at the time of ZIKV challenge showed no morbidity or mortality. However, the adoptive transfer of ARPV/ZIKV-primed T-cells into recipient IFN-αβR-/- mice resulted in a two-day median increase in survival time compared to controls. Altogether, these results suggest that ARPV/ZIKV-induced protection is primarily mediated by neutralizing antibodies at the time of challenge and that T-cells may play a comparatively minor but cumulative role in the protection observed. Lastly, ARPV/ZIKV-vaccinated Tcra KO mice, which are deficient in T-cell responses, experienced significant mortality post-challenge. These results suggest that ARPV/ZIKV-induced cell-mediated responses are critical for development of protective immune responses at vaccination. Despite the strong focus on neutralizing antibody responses to novel flavivirus vaccine candidates, these results suggest that cell-mediated responses induced by ISFV-based vaccines remain important to overall protective responses. |
| format | Article |
| id | doaj-art-bd110c4a28e84f0b8ea031cab51a8bdd |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bd110c4a28e84f0b8ea031cab51a8bdd2025-08-20T02:38:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-10-012010e101256610.1371/journal.ppat.1012566Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate.Danielle L PorierAwadalkareem AdamLin KangPawel MichalakJuselyn TupikMatthew A SantosManette TanelusKrisangel LópezDawn I AugusteChristy LeeIrving C AllenTian WangAlbert J AugusteFlaviviruses represent a significant global health threat and relatively few licensed vaccines exist to protect against them. Insect-specific flaviviruses (ISFVs) are incapable of replication in humans and have emerged as a novel and promising tool for flavivirus vaccine development. ISFV-based flavivirus vaccines have shown exceptional safety, immunogenicity, and efficacy, however, a detailed assessment of the correlates of protection and immune responses induced by these vaccines are still needed for vaccine optimization. Here, we explore the mechanisms of protective immunity induced by a previously created pre-clinical Zika virus (ZIKV) vaccine candidate, called Aripo/Zika (ARPV/ZIKV). In brief, immunocompromised IFN-αβR-/- mice passively immunized with ARPV/ZIKV immune sera experienced protection after lethal ZIKV challenge, although this protection was incomplete. ARPV/ZIKV-vaccinated IFN-αβR-/- mice depleted of CD4+ or CD8+ T-cells at the time of ZIKV challenge showed no morbidity or mortality. However, the adoptive transfer of ARPV/ZIKV-primed T-cells into recipient IFN-αβR-/- mice resulted in a two-day median increase in survival time compared to controls. Altogether, these results suggest that ARPV/ZIKV-induced protection is primarily mediated by neutralizing antibodies at the time of challenge and that T-cells may play a comparatively minor but cumulative role in the protection observed. Lastly, ARPV/ZIKV-vaccinated Tcra KO mice, which are deficient in T-cell responses, experienced significant mortality post-challenge. These results suggest that ARPV/ZIKV-induced cell-mediated responses are critical for development of protective immune responses at vaccination. Despite the strong focus on neutralizing antibody responses to novel flavivirus vaccine candidates, these results suggest that cell-mediated responses induced by ISFV-based vaccines remain important to overall protective responses.https://doi.org/10.1371/journal.ppat.1012566 |
| spellingShingle | Danielle L Porier Awadalkareem Adam Lin Kang Pawel Michalak Juselyn Tupik Matthew A Santos Manette Tanelus Krisangel López Dawn I Auguste Christy Lee Irving C Allen Tian Wang Albert J Auguste Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. PLoS Pathogens |
| title | Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. |
| title_full | Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. |
| title_fullStr | Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. |
| title_full_unstemmed | Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. |
| title_short | Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate. |
| title_sort | humoral and t cell mediated responses to an insect specific flavivirus based zika virus vaccine candidate |
| url | https://doi.org/10.1371/journal.ppat.1012566 |
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