Vaccine formulation basics
Vaccines comprise immunomodulators and antigens in particle formulations. Particle formulations play a key role in delivering antigen(s) and immunomodulator(s) to immune cell populations but require optimization of various properties (particle size, surface properties, etc.) for maximal benefit. Optimizing particle formulations has historically relied on a slow and tedious empirical process that delivers variable results.
SNAPvax overcomes limitations of conventional vaccine particle formulations by leveraging programmed self-assembly to ensure uniform nanoparticle formulations with any antigen, thereby eliminating the guesswork of vaccines of the past and ensuring rapid development of rationally designed vaccines with reliable activity.
Why SNAPvax?
SNAPvax ensures consistent formulations of antigens and immunomodulators in nanoparticles optimized for promoting antibody and T cell responses.
The example to the right shows T cell responses generated against seven unique tumor neoantigens using SNAPvax as compared with a conventional vaccine based on synthetic long peptide (SLP) antigens admixed with the adjuvant. As shown in this example, the conventional vaccine has variable properties (soluble or particulate) and leads to variable T cell responses, whereas SNAPvax ensures consistent nanoparticle formulations leading to T cell responses against all 7 of the neoantigens.
Efficient T cell priming
The ability of SNAPvax to improve T cell priming efficiency has been extensively studied. A multi-institutional study, including the Vaccine Research Center at the NIH, showed that SNAPvax induces T cell responses to 50% of predicted antigens, a >-5-fold increase as compared with conventional vaccine technologies. https://www.nature.com/articles/s41587-019-0390-x
Mechanism of action
Small particle sizes for optimal lymph node APC uptake
Enhanced immune responses with SNAPvax are, in part, driven by improved pharmacokinetics and antigen presenting cell (APC) uptake. SNAPvax’s small size (20 nm, diameter) enables passive trafficking to lymph nodes to access key populations of APCs, particularly dendritic cells (DCs), that promote T cell immunity.
Modular surface properties enable targeting of specific APC populations
SNAPvax enables a plug-and-play approach to evaluating how different characteristics, such as surface properties, impact uptake by different APC populations. Such studies have identified optimal surface properties for targeting APCs by different routes of vaccination.
Codelivered immunomodulator programs the type of immune response
The modularity of SNAPvax also allows for optimization of the codelivered immunomodulator to fine tune the immune response. Both SNAPvax cancer vaccine (CV) and SNAPvax tolerance vaccine (TV) have been optimized for the immunomodulator class, potency and number needed for the therapeutic application.
Linkers optimized for efficient antigen processing and presentation
Antigens must be processed and presented on the surface of APCs within the context of MHC molecules to enable priming and/or expansion of T cells. The amphiphilic peptides underlying SNAPvax include degradable linkers that are recognized by proteases in APCs, thereby enabling rapid antigen processing for efficient presentation to T cells.
Codelivery of antigen and immunomodulator ensures optimal responses
Antigens and immunomodulators must be codelivered to APCs for optimal T cell priming. To ensure codelivery, immunomodulators are covalently linked directly to the peptide antigens (see below) comprising SNAPvax and result in significantly higher T cell responses as compared with peptide antigens admixed with immunomodulators.
