posted on 2024-01-12, 20:34authored byBen S. Ou, Julie Baillet, Vittoria C. T.
M. Picece, Emily C. Gale, Abigail E. Powell, Olivia M. Saouaf, Jerry Yan, Anahita Nejatfard, Hector Lopez Hernandez, Eric A. Appel
Development of effective vaccines for infectious diseases
has been
one of the most successful global health interventions in history.
Though, while ideal subunit vaccines strongly rely on antigen and
adjuvant(s) selection, the mode and time scale of exposure to the
immune system has often been overlooked. Unfortunately, poor control
over the delivery of many adjuvants, which play a key role in enhancing
the quality and potency of immune responses, can limit their efficacy
and cause off-target toxicities. There is a critical need for improved
adjuvant delivery technologies to enhance their efficacy and boost
vaccine performance. Nanoparticles have been shown to be ideal carriers
for improving antigen delivery due to their shape and size, which
mimic viral structures but have been generally less explored for adjuvant
delivery. Here, we describe the design of self-assembled poly(ethylene
glycol)-b-poly(lactic acid) nanoparticles decorated
with CpG, a potent TLR9 agonist, to increase adjuvanticity in COVID-19
vaccines. By controlling the surface density of CpG, we show that
intermediate valency is a key factor for TLR9 activation of immune
cells. When delivered with the SARS-CoV-2 spike protein, CpG nanoparticle
(CpG-NP) adjuvant greatly improves the magnitude and duration of antibody
responses when compared to soluble CpG, and results in overall greater
breadth of immunity against variants of concern. Moreover, encapsulation
of CpG-NP into injectable polymeric-nanoparticle (PNP) hydrogels enhances
the spatiotemporal control over codelivery of CpG-NP adjuvant and
spike protein antigen such that a single immunization of hydrogel-based
vaccines generates humoral responses comparable to those of a typical
prime-boost regimen of soluble vaccines. These delivery technologies
can potentially reduce the costs and burden of clinical vaccination,
both of which are key elements in fighting a pandemic.