HPV 16 E6 Based DNA Immunisation Hinders Growth and Metastatic Activity of E6/E7 Expressing Cancer Cells by Inducing Specific CD4+ T Cell Response and Reducing the Inflammatory Background

  • Jansons, J. (Speaker)
  • Dace Skrastiņa (Co-author)
  • Alesja Dudorova (Co-author)
  • Elena Royo Rubio (Co-author)
  • Daria Avdoshina (Co-author)
  • Alina Nicolai (Co-author)
  • Svetlana Gebrila (Co-author)
  • Nazarovs, J. (Co-author)
  • Issagouliantis, M. (Co-author)

Activity: Talk or presentation types › Oral presentation

Description

Human papillomaviruses are responsible for >95% of cervical cancer (CC) cases, major risk factor is infection with HPV genotype 16 (HPV16). While HPV infections and associated cancers are preventable by prophylactic HPV vaccines, there is a need for therapeutic vaccine(s) to treat chronic HPV infections and associated CC. Promising vaccine components are viral oncoproteins E6/E7. Our aim was to evaluate immunogenicity in mice of DNA-immunogens encoding consensus HPV16 E6 and E7 and evaluate their potential to protect mice against E6/E7-expressing tumors.. Consensus sequence of E6/E7 genes of HPV16 was obtained after sequencing viral isolates from CC patients. DNA-immunogens were constructed by cloning E6- and E7-encoding DNA into eukaryotic expression vector pVax. Groups of BALB/c (n=5) mice were immunized with pVax1, or pVaxE6, or pVaxE7, or both administered as separate injections, and challenged by subcutaneous injections of murine adenocarcinoma 4T1luc2 cells made to express E6/E7. Assessment of immune response and tumor challenge were performed as described earlier (https://pubmed.ncbi.nlm.nih.gov/36612231/). . We detected CD4+ T-cell response against E6 with potential immune escape mutation R17G, but no E7-specific T-cell responses. Also, non-stimulated splenocytes of E6-immunized mice secreted IFN-γ and IL-2, whereas E7-immunized mice, only TNF-α indicating immune activation versus inflammation. E6-immunization caused reduction in tumor size and weight. Both E6- and E7-immunizations reduced the number of liver metastases. E6 also reduced organ infiltration by tumor cells, specifically, infiltration into lungs, the main site of metastatic activity in CC. Interestingly, E6-immunization restricted growth and metastatic activity of both E6/E7-expressing and parental adenocarcinoma cells.. The effect of E6 DNA-immunization may result from combination of innate and adaptive T-cell response to E6. The latter would explain therapeutic effect of E6-vaccination in the absence of detectable specific immune response observed in clinical trials. Our results are important for the design of therapeutic HPV vaccines. Supported by FLPP project lzp-2021/1-0484.
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

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