Combined antigen-adjuvant virus-like particle (VLP) vaccine platform for enhanced immune response.
- Chimeric VLPs (cVLPs) contain both antigen and adjuvant, thereby enhancing both cellular and humoral responses.
- cVLPs are safer than live replicating vectored vaccines because of their lack of infectivity.
- The cVLP manufacturing process is much shorter than current vaccine production.
Traditional vaccines are generally composed of dead or attenuated microbes that have lost their disease-causing properties, its toxins or one or more of its surface proteins. These classic prophylactic vaccines evoke a humoral immune response and are sometimes associated with an unfavorable safety profile. A major challenge in the design of both prophylactic and therapeutic vaccines is the identification of antigen presentation and delivery systems capable of rapidly stimulating both the humoral and cellular components of the immune system to elicit a strong and sustained immunity against different pathogen isolates. Vaccines that require booster shots like influenza and hepatitis B are ideal targets for cVLPs. HPV (Gardasil by Merck) and flu vaccine markets were $1.3B and $3.5B in 2010, respectively.
Researchers at Emory University have developed novel alternative technologies for vaccine production that would enable the rapid development of more effective vaccines. cVLP vaccines contain both antigen and adjuvant molecules in the same particulate structure, and are highly immunogenic, eliciting both cellular and humoral responses. They can be engineered via well-established DNA recombination techniques within a few weeks of the discovery and characterization of a new viral antigen. The subsequent manufacturing process can be completed in as little as 2 months compared to the 9 months typically required for existing vaccine production methods. The researchers have also constructed membrane-anchored forms of protein adjuvants including GM-CSF and a modified bacterial flagellin that are incorporated into the VLPs. These membrane-anchored adjuvants are significantly more effective than the corresponding soluble forms in enhancing stimulation of the immune response, because both the antigen and adjuvant are present in the VLPs and are delivered to the same antigen-presenting cell. In addition, flagellin-containing VLPs can activate either a surface receptor TLR5 or intracellular receptor NLRC4 (IPAF), potentially initiating two different innate signaling pathways simultaneously. In comparison, soluble flagellin cannot penetrate the cell membrane without the help of virulence factors and therefore is probably not sensed by intracellular receptors.
Influenza and HIV cVLPs and flagellin VLPs have been produced and tested in animal models and shown to elicit both cellular and humoral responses.