Do as the pathogens do

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Science Translational Medicine  27 Apr 2016:
Vol. 8, Issue 336, pp. 336ec68
DOI: 10.1126/scitranslmed.aaf7826

Mammalian immune systems have evolved to identify conserved structures termed pathogen-associated molecular patterns (PAMPs). The host’s antigen-presenting cells (APCs) identify PAMPs by using families of pattern-recognition receptors, most commonly Toll-like receptors (TLRs). Recent immunization research has focused on exploring TLR agonists as new immune-boosting adjuvants to improve vaccine potency. Exciting new work published by Siefert et al. shows that presentation of both the vaccine and TLR agonists has an impact on the intensity and nature of the resulting immune response.

Many researchers have designed biomaterials-based systems to release vaccines and adjuvants in a controllable manner over time in vitro. Unfortunately, the immune system commonly recognizes these systems as foreign and processes them much too quickly to carry out prolonged payload delivery. This research team decided to take a different approach; they leveraged the evolution of the immune system by engineering a composite vaccine-adjuvant delivery device that mimics a biological insult. In specific, they developed degradable polyester nanoparticles the size of the diameter of a single spherical bacterium (~200 nm) that possess an internal cargo of a model vaccine, ovalbumin (OVA), and bacterial CpG-rich DNA fragments (TLR9 agonists) and display bacterial cell wall components (monophosphoryl lipid A, a TLR4 agonist) on their surfaces. These artificial bacterial biomimetics activated APCs in vitro—as demonstrated by inducing a desirable proinflammatory cytokine profile and surface OVA presentation—and skewed OVA-specific immune responses in vivo toward a TH1 cellular immunity phenotype, which is desirable for this model vaccine. Also, using multiple TLR-expressing human embryonic kidney 293 (HEK293) cell lines as model cells, the authors showed that composite nanoparticles synergistically enhanced cellular expression of both their specific TLRs (TLR4 and TLR9) as well as others (TLR2 and TLR5) in a manner similar to that of bacterial pathogens (Escherichia coli, Listeria monocytogenes, and Salmonella typhimurium).

Although more studies with disease-specific vaccines are required to validate this system, the new study lays the groundwork for a biologically inspired device that leverages how the immune system has evolved to fight pathogens.

A. L. Siefert et al., Artificial bacterial biomimetic nanoparticles synergize pathogen-associated molecular patterns for vaccine efficacy. Biomaterials 10.1016/j.biomaterials.2016.03.039 (2016). [Full Text]

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