A novel virus-like particle platform which could transform vaccine antigen delivery and gene therapy
Virus-like particles (VLPs) have been used for several decades as scaffolds for the display of vaccine antigens. This has proven to be a highly effective strategy – selected antigens derived from diverse pathogens have been incorporated into VLP platforms and used as candidate vaccines against influenza, malaria, tuberculosis, and other infectious diseases.
The principle of VLP engineering is that a non-infectious particle, comprised of self-assembling coat proteins, forms a capsid which can be modified to incorporate individual antigens from other infectious agents.
VLPs are extremely effective in stimulating immune responses, a phenomenon attributable to the display of multiple antigen copies in a single particle.
Although this general approach is well established in vaccinology, and some examples have progressed to clinical trials, challenges remain in engineering viral capsid proteins to incorporate heterologous antigens.
A common approach is genetic fusion, where the antigen in question is joined to the capsid protein as a single polypeptide. This method is unreliable, however, arising from inaccuracies in predicting the consequences of protein engineering. Some tag-based methods have been developed, but they require engineering of the attached antigen.
This invention relates to a specific method for attachment of any combination of antigens to a modified VLP without any requirement for further modification of the scaffold. Moreover, a unique advantage is that it also enables the attachment of targeting antibody to the complex.
A separate avenue of investigation in vaccinology relates to the use of monoclonal antibodies against surface receptors common to dendritic cells (e.g. DEC205) which are attached to an antigen. The antigen-antibody complex can be delivered more effectively, and in a more managed fashion, to a specific subgroup of dendritic cells.
This kind of approach has the potential to improve immune responses to weak antigens, for example. Again, however, challenges persist in engineering antibodies and their cognate antigens to form a complex. This invention incorporates a method to do this in a facile and highly flexible manner, creating a universal platform for antigen display and delivery.
Obvious applications lie in the development of vaccines against diseases where immunogenic responses are poor (e.g. gonorrhoea) or in groups of individuals who generally exhibit weaker immune responses (such as a second generation COVID-19 vaccine tailored specifically for use in the elderly).
Moreover, it has potential beyond vaccine design, as a general method for delivery of nucleic acid-based therapies to specific cells through antibody-mediated targeting.