Related Experiment Video
Updated: Aug 14, 2026
Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors
K R Irvine1, R S Chamberlain, E P Shulman
1Surgery Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892-1502, USA.
Background:
The identification of tumor-associated antigens and the cloning of DNA sequences encoding them have enabled the development of anticancer vaccines. Such vaccines target tumors by stimulating an immune response against the antigens. One method of vaccination involves the delivery of antigen-encoding DNA sequences, and a number of recombinant vectors have been used for this purpose. To optimize the efficacy of recombinant vaccines, we compared primary and booster treatment regimens that used a single vector (i.e., homologous boosting) with regimens that used two different vectors (i.e., heterologous boosting).
Methods:
Pulmonary tumors (experimental metastases) were induced in BALB/c mice inoculated with CT26.CL25 murine colon carcinoma cells, which express recombinant bacterial beta-galactosidase (the model antigen). Protocols for subsequent vaccination used three vectors that encoded beta-galactosidase--vaccinia (cowpox) virus, fowlpox virus, naked bacterial plasmid DNA. Mouse survival was evaluated in conjunction with antibody and cytotoxic T-lymphocyte responses to beta-galactosidase.
Results:
Heterologous boosting resulted in significantly longer mouse survival than homologous boosting (all P<.0001, two-sided). Potent antigen-specific cytotoxic T lymphocytes were generated following heterologous boosting with poxvirus vectors. This response was not observed with any of the homologous boosting regimens. Mice primed with recombinant poxvirus vectors generated highly specific antibodies against viral proteins.
Conclusions:
The poor efficacy of homologous boosting regimens with viral vectors was probably a consequence of the induction of a strong antiviral antibody response. Heterologous boosting augmented antitumor immunity by generating a strong antigen-specific cytotoxic T-lymphocyte response. These data suggest that heterologous boosting strategies may be useful in increasing the efficacy of recombinant DNA anticancer vaccines that have now entered clinical trials.
Insights
Heterologous boosting with different vaccine vectors significantly improved anticancer vaccine efficacy and mouse survival compared to homologous boosting. This strategy enhances antitumor immunity by generating potent cytotoxic T-lymphocyte responses.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Anticancer vaccines utilize tumor-associated antigens to stimulate immune responses.
- Recombinant vectors deliver antigen-encoding DNA sequences for vaccination.
- Optimizing vaccine efficacy involves comparing homologous and heterologous boosting regimens.
Purpose of the Study:
- To compare the efficacy of homologous and heterologous boosting strategies for recombinant DNA anticancer vaccines.
- To evaluate the impact of different vector combinations on immune responses and survival.
Main Methods:
- Experimental pulmonary metastases were induced in BALB/c mice using CT26.CL25 colon carcinoma cells.
- Mice were vaccinated using three vectors encoding beta-galactosidase: vaccinia virus, fowlpox virus, and plasmid DNA.
- Mouse survival, antibody responses, and cytotoxic T-lymphocyte (CTL) activity against beta-galactosidase were assessed.
Main Results:
- Heterologous boosting significantly increased mouse survival compared to homologous boosting (P<.0001).
- Potent, antigen-specific CTL responses were induced by heterologous boosting with poxvirus vectors.
- Homologous boosting regimens did not elicit the observed CTL response and led to high antibody responses against viral proteins.
Conclusions:
- Homologous boosting with viral vectors may be limited by strong antiviral antibody induction.
- Heterologous boosting enhances antitumor immunity by promoting antigen-specific CTL responses.
- Heterologous boosting strategies show promise for improving the efficacy of clinical anticancer DNA vaccines.
More Related Videos
12:42Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
08:10Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector
Published on: November 28, 2018
Related Concept Videos
01:09Recombinant DNA
01:27Tumor Immunotherapy
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...