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Preclinical Immunogenicity and Efficacy Studies for Therapeutic Vaccines for Human Papillomavirus-Type-16-Associated Cancer. | LitMetric

AI Article Synopsis

  • * The vaccines used fusion proteins linked to herpes simplex virus (HSV)-1 glycoprotein D, which helps activate T cells, enhancing immune responses against HPV antigens.
  • * Findings revealed that expressing HPV antigens within HSV-1 gD was crucial for vaccine success, and surprisingly, including E2 boosted T cell responses and improved tumor regression in model cancers.

Article Abstract

The objective of this study was to conduct preclinical immunogenicity and efficacy studies with several therapeutic vaccines for human papillomavirus (HPV)-16-associated cancers expressing the early antigens E5, E6, and E7 with or without E2. The viral oncoproteins were either expressed by themselves as fusion proteins or the fusion proteins were inserted genetically into herpes simplex virus (HSV)-1 glycoprotein D (gD) which, upon binding to the herpes virus entry mediator (HVEM), inhibits an early T cell checkpoint mediated by the B and T cell mediator (BTLA). This, in turn, lowers the threshold for T cell activation and augments and broadens CD8 T cell responses to the antigens. The fusion antigens were expressed by chimpanzee adenovirus (AdC) vectors. Expression of the HPV antigens within gD was essential for vaccine immunogenicity and efficacy against challenge with TC-1 cells, which express E7 and E6 of HPV-16 but neither E5 nor E2. Unexpectedly, inclusion of E2 increased both CD8 T cell responses to the other oncoproteins of HPV-16 and the effectiveness of the vaccines to cause the regression of sizable TC-1 tumors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209626PMC
http://dx.doi.org/10.3390/vaccines12060616DOI Listing

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