Abstract
Vaccines are critical for combating infectious diseases across the globe. Influenza, for example, kills roughly 500,000 people annually worldwide, despite annual vaccination campaigns. Efficacious vaccines must elicit a robust and durable antibody response, and poor efficacy often arises from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system's natural response to extended pathogen exposure during infection by designing an easily administered slow‐delivery influenza vaccine platform. We utilized an injectable and self‐healing polymer‐nanoparticle (PNP) hydrogel platform to prolong the co‐delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique dynamic physical characteristics whereby physicochemically distinct influenza hemagglutinin antigen and a toll‐like receptor 7/8 agonist adjuvant could be co‐delivered over prolonged timeframes that were tunable through simple alteration of the gel formulation. We show a relationship between hydrogel physical properties and the resulting immune response to immunization. When administered in mice, hydrogel‐based vaccines demonstrated enhancements in the magnitude and duration of humoral immune responses compared to alum, a widely used clinical adjuvant system. We found stiffer hydrogel formulations exhibited slower release and resulted in the greatest improvements to the antibody response while also enabling significant adjuvant dose sparing. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of influenza subunit vaccines.
Highlights
Even our ever-changing yearly flu vaccines are insufficient to stop the roughly 500,000 deaths occurring annually worldwide from seasonal influenza
While reports indicate that subunit vaccines comprising multiple toll-like receptor agonists (TLRa) molecules elicit better immune memory and stronger antibody responses,[8,9,10] it was recently reported that numerous highly potent adjuvant systems increase binding antibody titer but do not affect levels of somatic hypermutation when used in HIV vaccines in non-human primates.[11]
Our previous work has shown that PNP hydrogels can be loaded with vaccine components for injection and provide extended co-delivery of physicochemically disctinct subunit vaccine cargo comprising ovalbumin and poly(I:C)
Summary
Even our ever-changing yearly flu vaccines are insufficient to stop the roughly 500,000 deaths occurring annually worldwide from seasonal influenza. New influenza strains with all of the hallmarks of a pandemic threat continue to emerge, including the recently described Eurasian avian-like H1N1 swine influenza strain dubbed G4.1 A successful vaccine providing potent and durable humoral immune responses against influenza must generate broadly neutralizing antibodies against the viral envelope protein hemagglutinin (HA).[2,3] High quality antibodies are generally characterized by high degrees of somatic hypermutation and commensurate affinity maturation that generally occurs in germinal centers (GCs) in the lymph nodes following immunization. These results indicate that adjuvants alone, even potent TLRa adjuvants, may not be sufficient to spur high quality immune responses, highlighting that a critical need exists for improved spatiotemporal control over vaccine delivery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
