Related Experiment Video
Updated: Mar 19, 2026
Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
Chimeric HBcAg virus-like particles presenting a HPV 16 E7 epitope significantly suppressed tumor progression through
Xiaojie Chu1, Yang Li1, Qiong Long1
1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, People's Republic of China; Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, People's Republic of China; Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People's Republic of China.
Background:
Therapeutic human papillomavirus (HPV) vaccines are currently being developed. However, no therapeutic efficacy has been achieved in clinical trials for the treatment of cervical intraepithelial neoplasia or cancer. One of the important issues in increasing vaccine efficacy is determining the best way to enhance tumor antigen-specific cellular immune responses. This study aimed to explore the virus-like particles (VLPs) of hepatitis B core antigen (HBcAg) as potential therapeutic vaccine carriers and to assess its immunological characteristics.
Methods:
Chimeric VLPs presenting a HPV 16 cytotoxic T lymphocytes epitope E749-57 (amino acid 49-57 of the E7 protein) were prepared using recombinant genes. C57BL/6 mice were immunized with VLPs and grafted with tumor cells TC-1 which is an E7-expressing tumorigenic cell line. The dynamic tumor growth was monitored and anti-tumor immune responses were investigated.
Results:
Using a preventive strategy, immunization with VLPs resulted in nearly complete suppression of tumor growth. In treatment studies, VLP immunization significantly suppressed the tumor progression in mice carrying 2-3 mm tumors and in those bearing even larger tumors with diameters up to 8-9 mm. The VLP structure was shown to be important to induce vigorous antitumor immunity and effects. In immunized mice, enhanced E749-57-specific cellular immune responses were evidenced by increased interferon (IFN)-γ expression and decreased interleukin (IL)-4 expression in splenic lymphocytes, as well as an elevated number of effector cells expressing IFN-γ in response to the in vitro stimulation of the specific peptide E749-57. In addition, effective immune memory after VLP immunization was maintained for at least 16 weeks, preventing significant tumor growth after subsequent TC-1 challenge.
Conclusion:
While VLPs were highly immunogenic in stimulating humoral immunity, our results strongly indicated that VLPs, such as HBcAg particles, might also be potent therapeutic vaccine carriers to elicit robust cellular immune responses, even in the immunosuppressive microenvironment of a tumor.
Insights
Hepatitis B core antigen virus-like particles (VLPs) show promise as therapeutic vaccine carriers. These VLPs effectively suppressed tumor growth and enhanced anti-tumor cellular immunity in preclinical models, suggesting potential for cancer treatment.
Area of Science:
- Immunology
- Vaccinology
- Oncology
Background:
- Therapeutic human papillomavirus (HPV) vaccines are under development, but clinical efficacy for cervical neoplasia and cancer remains elusive.
- Enhancing tumor antigen-specific cellular immune responses is crucial for improving vaccine effectiveness.
- Hepatitis B core antigen virus-like particles (HBcAg VLPs) are explored as novel vaccine carriers.
Purpose of the Study:
- To investigate HBcAg VLPs as carriers for therapeutic cancer vaccines.
- To assess the immunological characteristics and anti-tumor efficacy of chimeric VLPs presenting a HPV 16 epitope.
Main Methods:
- Chimeric VLPs displaying a HPV 16 E7 epitope were constructed using recombinant DNA technology.
- Mice were immunized with VLPs and challenged with E7-expressing TC-1 tumor cells.
- Tumor growth, anti-tumor immune responses, and immune memory were evaluated.
Main Results:
- VLP immunization demonstrated significant tumor growth suppression in both preventive and therapeutic settings, even for established tumors.
- VLPs induced robust E7-specific cellular immunity, characterized by increased IFN-γ and decreased IL-4 production in lymphocytes.
- Effective immune memory was established, providing long-term protection against tumor recurrence.
Conclusions:
- HBcAg VLPs are potent carriers for therapeutic cancer vaccines, capable of eliciting strong cellular immune responses.
- These VLPs can overcome the immunosuppressive tumor microenvironment.
- VLPs hold significant potential for developing effective therapeutic vaccines against HPV-associated cancers.
More Related Videos
07:25Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
