Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate
Abstract Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platfor...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47086-9 |
| _version_ | 1827723224341807104 |
|---|---|
| author | Manette Tanelus Krisangel López Shaan Smith John A. Muller Danielle L. Porier Dawn I. Auguste William B. Stone Sally L. Paulson Albert J. Auguste |
| author_facet | Manette Tanelus Krisangel López Shaan Smith John A. Muller Danielle L. Porier Dawn I. Auguste William B. Stone Sally L. Paulson Albert J. Auguste |
| author_sort | Manette Tanelus |
| collection | DOAJ |
| description | Abstract Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platform for vaccine development and diagnostic applications. Here, we further explore the safety, immunogenicity, and efficacy of a chimeric ISFV-Zika vaccine candidate, designated Aripo-Zika (ARPV/ZIKV). Our results show a near-linear relationship between increased dose and immunogenicity, with 1011 genome copies (i.e., 108 focus forming units) being the minimum dose required for protection from ZIKV-induced morbidity and mortality in mice. Including boosters did not significantly increase the short-term efficacy of ARPV/ZIKV-vaccinated mice. We also show that weanling mice derived from ARPV/ZIKV-vaccinated dams were completely protected from ZIKV-induced morbidity and mortality upon challenge, suggesting efficient transfer of maternally-derived protective antibodies. Finally, in vitro coinfection studies of ZIKV with Aripo virus (ARPV) and ARPV/ZIKV in African green monkey kidney cells (i.e., Vero-76) showed that ARPV and ARPV/ZIKV remain incapable of replication in vertebrate cells, despite the presence of active ZIKV replication. Altogether, our data continue to support ISFV-based vaccines, and specifically the ARPV backbone is a safe, immunogenic and effective vaccine strategy for flaviviruses. |
| first_indexed | 2024-03-10T21:57:18Z |
| format | Article |
| id | doaj.art-4221208a55c3411a9bdee142c48b5182 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:57:18Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4221208a55c3411a9bdee142c48b51822023-11-19T13:04:28ZengNature PortfolioScientific Reports2045-23222023-11-0113111010.1038/s41598-023-47086-9Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidateManette Tanelus0Krisangel López1Shaan Smith2John A. Muller3Danielle L. Porier4Dawn I. Auguste5William B. Stone6Sally L. Paulson7Albert J. Auguste8Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State UniversityAbstract Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platform for vaccine development and diagnostic applications. Here, we further explore the safety, immunogenicity, and efficacy of a chimeric ISFV-Zika vaccine candidate, designated Aripo-Zika (ARPV/ZIKV). Our results show a near-linear relationship between increased dose and immunogenicity, with 1011 genome copies (i.e., 108 focus forming units) being the minimum dose required for protection from ZIKV-induced morbidity and mortality in mice. Including boosters did not significantly increase the short-term efficacy of ARPV/ZIKV-vaccinated mice. We also show that weanling mice derived from ARPV/ZIKV-vaccinated dams were completely protected from ZIKV-induced morbidity and mortality upon challenge, suggesting efficient transfer of maternally-derived protective antibodies. Finally, in vitro coinfection studies of ZIKV with Aripo virus (ARPV) and ARPV/ZIKV in African green monkey kidney cells (i.e., Vero-76) showed that ARPV and ARPV/ZIKV remain incapable of replication in vertebrate cells, despite the presence of active ZIKV replication. Altogether, our data continue to support ISFV-based vaccines, and specifically the ARPV backbone is a safe, immunogenic and effective vaccine strategy for flaviviruses.https://doi.org/10.1038/s41598-023-47086-9 |
| spellingShingle | Manette Tanelus Krisangel López Shaan Smith John A. Muller Danielle L. Porier Dawn I. Auguste William B. Stone Sally L. Paulson Albert J. Auguste Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate Scientific Reports |
| title | Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate |
| title_full | Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate |
| title_fullStr | Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate |
| title_full_unstemmed | Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate |
| title_short | Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate |
| title_sort | exploring the immunogenicity of an insect specific virus vectored zika vaccine candidate |
| url | https://doi.org/10.1038/s41598-023-47086-9 |
| work_keys_str_mv | AT manettetanelus exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT krisangellopez exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT shaansmith exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT johnamuller exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT daniellelporier exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT dawniauguste exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT williambstone exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT sallylpaulson exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate AT albertjauguste exploringtheimmunogenicityofaninsectspecificvirusvectoredzikavaccinecandidate |