bVaccination remains the most effective public health tool to prevent infectious diseases. Many vaccines are marginally effective and need enhancement for immunocompromised, elderly, and very young populations. To enhance immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new delivery method. VacSIM solution can easily be mixed with antigens, organisms, and adjuvants for injection. Postinjection, the peptides self-assemble into hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in the aqueous phase. We believe the depot provides slow release of immunogens, leading to increased activation of antigen-presenting cells that then drive enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type response following immunization with VacSIM, which was driven further toward Th1 with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2 environments, respectively. Restimulation of splenocytes suggests that VacSIM does not cause an immediate proinflammatory response in the host. Overall, these results suggest that VacSIM, as a new delivery method, has the potential to enhance immunogenicity and efficacy of numerous vaccines. Vaccines remain the single greatest public health tool to combat infectious diseases. Vaccine formulation and delivery are key to the ability of vaccines to induce the desired immune responses. One goal of vaccine delivery is to present vaccine antigens in a manner that enhances antigen-presenting-cell (APC) activation, leading to antigen/organism uptake and processing of vaccine antigen(s). Delivery methods or adjuvants that safely enhance vaccine immunogenicity/efficacy are desirable for vaccines that are marginally effective and for vaccines administered to low responders or immunocompromised populations. Additional goals are to reduce the number of doses required to induce effective, vaccine responses and to reduce the amount of vaccine/dose, especially when a single dose of vaccine is administered, as with annual influenza vaccines. Lastly, in pandemics, a vaccine that produces high titers after a single administration would be beneficial. Recent advances in the understanding of how innate mechanisms influence adaptive immunity have led to more rational design in the development of new vaccine adjuvants and delivery systems.Aluminum salts were the first adjuvants licensed for human vaccines in the 1920s. The licensure of non-aluminum salt adjuvants took an additional 80 years (1). One reason for this long gap is that the principles of adjuvant activit...
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.
Influenza is a global health issue causing considerable economic burden. Seasonal epidemics of this acute viral infection spread rapidly with unpredictable morbidity. Regular vaccination remains the most effective prevention and as such, there is tremendous need for new technologies focused on improving immunogenicity and efficacy of seasonal flu vaccines. VacSIM™, which stands for Vaccine Self-assembling Immune Matrix, represents a new method of vaccine delivery incorporating an inert biopolymer with unique biophysical properties. It can be stored at 4-22°C, as a viscous-liquid and is flexible enough to incorporate various antigens, adjuvants or organisms for vaccine delivery. Post-injection VacSIM™ undergoes a phase shift to a semi-solid gel, forming a temporary depot of concentrated vaccine components. This gel-matrix depot may slow clearance of the vaccine, simultaneously enabling time-released delivery of the vaccine. We believe the latter increases activation of antigen presenting cells. Mice vaccinated with whole inactivated influenza (A/Puerto Rico/08/34) or with recombinant nucleoprotein via VacSIM™, had an increased humoral response, greater protection from lethal influenza challenge and improved viral clearance from lungs. Studies with other candidate vaccine antigens suggest VacSIM™ is capable of enhancing the immunogenicity and efficacy of a wide variety of vaccines.
Vaccination remains the most effective public health tool to prevent infectious disease. However, many vaccines remain marginally effective, especially for immune-compromised populations. To enhance vaccine immunogenicity, we exploited the biphasic property of certain synthetic oligopeptides to create a new vaccine delivery method, VacSIM (vaccine self-assembling immune matrix). Vaccine components are easily mixed with the VacSIM solution for injection, after which the peptides self-assemble into hydrated nanofiber gel-matrices, forming a vaccine depot. Thus, we have a non-viral, inert, biodegradable delivery system, not requiring formulation, which we can use to deliver a multitude of vaccines. Analogous to a treat-dispensing dog toy, VacSIM is a carrier for vaccine components, allowing for gradual release, rather than immediate administration. We believe this depot attracts antigen presenting cells, driving enhanced vaccine-specific responses that improve both the quantity and quality of the response. We have tested this delivery platform with live bacterial vectors, inactivated virus and multiple recombinant protein vaccines. Shown here, VacSIM augments vaccine responses to the recombinant Hepatitis B surface antigen and recombinant HIV Envelope in 2 strains of mice. Enhancement of vaccine responses by VacSIM administration could represent a fundamental paradigm shift in how vaccines are delivered.
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