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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Encapsulation of adenovirus serotype 5 in anionic lecithin liposomes using a bead-based immunoprecipitation technique
Natalie Mendez1, Vanessa Herrera2, Lingzhi Zhang3
1Department of Materials Science and Engineering, University of California, San Diego (UCSD), La Jolla, CA, USA.
Abstract:
Oncolytic viruses (OVs) constitute a promising class of cancer therapeutics which exploit validated genetic pathways known to be deregulated in many cancers. To overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, a method for liposomal encapsulation of adenovirus has been developed. The encapsulation of adenovirus in non-toxic anionic lecithin-cholesterol-PEG liposomes ranging from 140 to 180 nm in diameter have been prepared by self-assembly around the viral capsid. The encapsulated viruses retain their ability to infect cancer cells. Furthermore, an immunoprecipitation (IP) technique has shown to be a fast and effective method to extract non-encapsulated viruses and homogenize the liposomes remaining in solution. 78% of adenovirus plaque forming units were encapsulated and retained infectivity after IP processing. Additionally, encapsulated viruses have shown enhanced transfection efficiency up to 4 × higher compared to non-encapsulated Ads. Extracting non-encapsulated viruses from solution may prevent an adverse in vivo immune response and may enhance treatment for multiple administrations.
Insights
Liposomal encapsulation of adenovirus protects the virus and enhances its cancer-fighting ability. This method shields the oncolytic virus (OV) from immune responses, improving potential cancer treatments.
Area of Science:
- Oncolytic virotherapy
- Nanomedicine
- Cancer therapeutics
Background:
- Oncolytic viruses (OVs) are promising cancer therapeutics targeting deregulated cancer pathways.
- Developing OVs that evade immune responses is crucial for treating primary and metastatic tumors.
Purpose of the Study:
- To develop a method for liposomal encapsulation of adenovirus (Ad) to improve its therapeutic potential.
- To assess the infectivity, transfection efficiency, and immune response potential of encapsulated OVs.
Main Methods:
- Adenovirus was encapsulated in anionic lecithin-cholesterol-PEG liposomes (140-180 nm) via self-assembly.
- Immunoprecipitation (IP) was used to extract non-encapsulated viruses and homogenize liposomes.
- Infectivity and transfection efficiency of encapsulated and non-encapsulated Ads were compared.
Main Results:
- Liposomal encapsulation protected adenovirus, with 78% of plaque-forming units encapsulated and retaining infectivity after IP processing.
- Encapsulated Ads demonstrated up to 4x higher transfection efficiency compared to non-encapsulated Ads.
- The IP method effectively removed non-encapsulated viruses, potentially mitigating adverse immune responses.
Conclusions:
- Liposomal encapsulation is a viable strategy to enhance oncolytic adenovirus efficacy and safety.
- This approach may enable improved cancer treatment, including multiple administrations, by reducing immunogenicity.
- Further research into liposome-decorated OVs could advance cancer therapy.
