Vaccination prevents approximately 1.5 million deaths each year and is widely recognized as the most effective way to prevent infectious diseases. However, almost all vaccines require more than one injection to elicit protective immunity, with several months or even over a year between injections. Such a dosing regimen represents a great challenge to further improve vaccine coverage globally, especially in developing countries where healthcare infrastructure and logistical systems are limited. World Health Organization (WHO) reports showed that 10 million children received at least one dose of vaccine but failed to receive the necessary booster shots. The COVID-19 pandemic further highlights the challenges of administering a multi-dose vaccine regimen.
A delivery system that could elicit protective immunity with a single injection holds great potential to improve global vaccine coverage without the need to change the vaccine infrastructure. To address this grand challenge, Lu developed microfabricated polylactic-co-glycolic acid (PLGA, an FDA-approved polymer used as biodegradable sutures) particles that remain at the site of injection and release encapsulated cargos as a programmable sequence of pulses at pre-determined time points. A single injection of PLGA microparticles mimics multiple syringe injections over weeks to months. They further addressed the challenge of vaccine instability during particle fabrication and post administration by precisely tuning the composition and ratio of excipients, therefore paving the way for single injection vaccination.
A single injection of inactivated polio vaccine-loaded microparticles released three doses at 0, 1, and 2 months, and elicited non-inferior neutralizing antibody titers in an animal model compared to three bolus injections. This platform is also compatible with different types of vaccines, including nucleic acids, recombinant proteins, and inactivated viruses, thus allowing this platform to be adapted to nearly any vaccine campaign aiming to simplify administration and improve the overall immunization rate.
Besides delivering vaccines, these PLGA microparticles have broad applications in many chronic diseases. For example, Lu demonstrated that PLGA microparticles could be used to deliver cancer immunotherapeutics-STING agonist, which requires frequent intratumoral injections over months and is associated with an increased risk of metastasis and poor patient adherence. A single intratumoral injection of STING agonist-loaded microparticles inhibits tumor growth and prolongs survival as effectively as multiple soluble doses in several tumor models. PLGA microparticles also expanded the scope of STING agonist-based therapy to hard-to-reach tumors and as an adjuvant therapy to prevent tumor recurrence after surgery.
