Enhancing immunogenicity of recombinant protein vaccines in mice with vaccine self-assembling immune matrix, a non-viral delivery platform (VAC8P.1059)

Abstract

Vaccination remains the most effective public health tool to prevent infectious disease. Many vaccines are marginally effective in general, or are less efficacious when used in immune-compromised populations. To enhance vaccine immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create a new vaccine delivery method, VacSIM (vaccine self-assembling immune matrix). Vaccine components are mixed with the VacSIM solution for injection, after which the (RADA)4 peptides self-assemble into hydrated nanofiber gel-matrices, forming a vaccine depot with the vaccine antigens in the aqueous phase, allowing for slow-release of vaccine components over time. Thus, we have a non-viral, inert, biodegradable delivery system, not requiring formulation that can deliver a multitude of vaccines. We hypothesize that slow-release of vaccine components provides antigen persistence, driving enhanced vaccine-specific responses that are improved in both quantity and quality of the response. We have tested VacSIM with live bacterial vectors, inactivated virus and multiple recombinant protein vaccines. Shown here, VacSIM improves vaccine responses to protein immunogens in 2 strains of mice and remains stable after long-term storage. In addition, VacSIM by itself does not activate antigen presenting cells. Enhancement of vaccine responses by VacSIM administration could represent a fundamental paradigm shift in how vaccines are delivered.