62P - Evaluation the effect of Brucella abortus RB51 lipopolysaccharide as an adjuvant on the efficiency of HPV-16 L1 and HPV-16 E7 DNA vaccines in C57BL...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Lymphomas
Haematologic Malignancies
Translational Research
Presenter Hoorieh Soleimanjahi
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors H. Soleimanjahi1, M. Shirmohammadi1, Z. Kianmehr2, H. Karimi1
  • 1Virology, Tarbiat Modares University, 14115-331 - Teheran/IR
  • 2Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran, - - Teheran/IR

Abstract

Background

Cervical cancer is the second most common cancer in women worldwide and is highly associated with high-risk human papillomavirus (HPV) infection, most often HPV16. Infection caused by HPV requires therapeutic vaccine with the induction of cellular immune responses. However, DNA vaccine alone have limited immunogenicity and therefore, these strategies are needed for increasing their potency such as using an adjuvant. In this study, we used two HPV-16 therapeutic DNA vaccines, pcDNA3.1-E7 and pcDNA3.1-L1, assisted with Brucella abortus RB51 lipopolysaccharide (LPS) as an adjuvant that has less toxicity and no pyrogenic properties in comparison to other bacterial LPS. The aim of this study was the comparison of the efficacy of Brucella abortus RB51 along with two DNA vaccines, pcDNA3.1-E7 and pcDNA3.1-L1, in induction of CTL responses.

Methods

In this study, TC-1 cells were injected subcutaneously to the back of C57BL/6 mice in a volume of 100 μL. For DNA vaccine immunizations, mice were immunized intradermally with a total of 50 μg HPV DNA vaccine containing HPV-16 E7 and HPV-16 L1 DNA alone, or along with B.abortus RB51 LPS (R-LPS). To determine T-cell immune responses, different cytokines such as IFN-γ and IL-4 were evaluated.

Results

Based on the results immunization with pcDNA3.1-E7 or pcDNA3.1-L1 alone could induce strong cellular immune responses, but comparative assessments of these vaccines show that co-administration of HPV-16 E7 and HPV-16 L1 DNA vaccines assisted with R-LPS induced a stronger antigen-specific cellular immune responses and protect mice against TC-1 tumor cell challenges.

Conclusions

The administration of B.abortus RB51 LPS (R-LPS) along with E7&L1 gene plasmid induced HPV16-specific cellular immune responses and protect against TC-1 induced tumor in vivo. We showed that this vaccine was immunogenic, and protective in the TC-1 tumor model. Furthermore, B.abortus RB51 LPS (R-LPS) may be an adequate alternative to enhancing of therapeutic effect of HPV-16 E7 and HPV-16 L1 DNA vaccine.

Clinical trial identification

NA

Legal entity responsible for the study

Tarbiat Modares University

Funding

Tarbiat Modares University

Disclosure

All authors have declared no conflicts of interest.