Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods
Abstract Background We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
|
| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-024-01338-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850085947212824576 |
|---|---|
| author | Shiwen Peng Darrell Fan Hsin-Fang Tu Michelle Cheng Rebecca C. Arend Kimberly Levinson Julia Tao Richard B. S. Roden Chien-Fu Hung T.-C. Wu |
| author_facet | Shiwen Peng Darrell Fan Hsin-Fang Tu Michelle Cheng Rebecca C. Arend Kimberly Levinson Julia Tao Richard B. S. Roden Chien-Fu Hung T.-C. Wu |
| author_sort | Shiwen Peng |
| collection | DOAJ |
| description | Abstract Background We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced, stable, and well tolerated, their potency is limited by the delivery efficiency. Here we compared three different IM delivery strategies, including intramuscular (IM) injection, either with a needle alone or with electroporation at the injection site, and a needle-free injection system (NFIS), for their ability to elicit gene expression and to improve the potency of pBI-11 DNA vaccine. Results We found that electroporation after IM injection significantly increases gene expression from a luciferase-encoding DNA construct compared to IM injection alone or NFIS. We also showed that single administration of pBI-11 DNA via electroporation-mediated delivery generates the greatest increase in HPV antigen-specific CD8 + T cell-mediated immune responses, resulting in the most potent antitumor effect compared to the other two methods. We further compared the response to three repeat immunizations via each of these different methods. We found that electroporation-mediated delivery of pBI-11 DNA generates the greatest HPV antigen-specific CD8 + T cell immune responses and therapeutic antitumor effects compared to the other two methods. Monitoring of mouse behaviors and body weight, and necropsy indicated that electroporation-mediated delivery of clinical grade pBI-11 DNA vaccine was well-tolerated and presented no evident local or systemic toxicity. Conclusions These findings provide rationale for clinical testing of pBI-11 DNA vaccine delivered by electroporation for the control of HPV16/18-associated infections and/or cancers. |
| format | Article |
| id | doaj-art-bce64232270142db9d2b65a88a789cb7 |
| institution | DOAJ |
| issn | 2045-3701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-bce64232270142db9d2b65a88a789cb72025-08-20T02:43:36ZengBMCCell & Bioscience2045-37012024-12-0114111510.1186/s13578-024-01338-xImproved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methodsShiwen Peng0Darrell Fan1Hsin-Fang Tu2Michelle Cheng3Rebecca C. Arend4Kimberly Levinson5Julia Tao6Richard B. S. Roden7Chien-Fu Hung8T.-C. Wu9Department of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Obstetrics and Gynecology, University of Alabama at Birmingham, O’Neal Comprehensive Cancer CenterDepartment of Oncology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineDepartment of Pathology, Johns Hopkins School of MedicineAbstract Background We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced, stable, and well tolerated, their potency is limited by the delivery efficiency. Here we compared three different IM delivery strategies, including intramuscular (IM) injection, either with a needle alone or with electroporation at the injection site, and a needle-free injection system (NFIS), for their ability to elicit gene expression and to improve the potency of pBI-11 DNA vaccine. Results We found that electroporation after IM injection significantly increases gene expression from a luciferase-encoding DNA construct compared to IM injection alone or NFIS. We also showed that single administration of pBI-11 DNA via electroporation-mediated delivery generates the greatest increase in HPV antigen-specific CD8 + T cell-mediated immune responses, resulting in the most potent antitumor effect compared to the other two methods. We further compared the response to three repeat immunizations via each of these different methods. We found that electroporation-mediated delivery of pBI-11 DNA generates the greatest HPV antigen-specific CD8 + T cell immune responses and therapeutic antitumor effects compared to the other two methods. Monitoring of mouse behaviors and body weight, and necropsy indicated that electroporation-mediated delivery of clinical grade pBI-11 DNA vaccine was well-tolerated and presented no evident local or systemic toxicity. Conclusions These findings provide rationale for clinical testing of pBI-11 DNA vaccine delivered by electroporation for the control of HPV16/18-associated infections and/or cancers.https://doi.org/10.1186/s13578-024-01338-xHuman papillomavirusHPV16HPV18E6E7DNA vaccine |
| spellingShingle | Shiwen Peng Darrell Fan Hsin-Fang Tu Michelle Cheng Rebecca C. Arend Kimberly Levinson Julia Tao Richard B. S. Roden Chien-Fu Hung T.-C. Wu Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods Cell & Bioscience Human papillomavirus HPV16 HPV18 E6 E7 DNA vaccine |
| title | Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods |
| title_full | Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods |
| title_fullStr | Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods |
| title_full_unstemmed | Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods |
| title_short | Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods |
| title_sort | improved efficacy of therapeutic hpv dna vaccine using intramuscular injection with electroporation compared to conventional needle and needle free jet injector methods |
| topic | Human papillomavirus HPV16 HPV18 E6 E7 DNA vaccine |
| url | https://doi.org/10.1186/s13578-024-01338-x |
| work_keys_str_mv | AT shiwenpeng improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT darrellfan improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT hsinfangtu improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT michellecheng improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT rebeccacarend improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT kimberlylevinson improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT juliatao improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT richardbsroden improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT chienfuhung improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods AT tcwu improvedefficacyoftherapeutichpvdnavaccineusingintramuscularinjectionwithelectroporationcomparedtoconventionalneedleandneedlefreejetinjectormethods |