Abstract:
:New adjuvants and delivery strategies are needed to optimize the ability of protein-based vaccines to elicit CD8(+) T cell responses. We have developed a model vaccine formulation containing ovalbumin (OVA) and the double-stranded RNA analog poly(inosinic acid)-poly(cytidylic acid) (poly(I:C)), a TLR3 agonist. OVA and poly(I:C) were each ion-paired to cetyltrimethylammonium bromide (CTAB) to produce hydrophobic complexes, which were co-encapsulated in pH-sensitive polyketal (PK3) microparticles (1-3 microm) using a single emulsion method. Loading levels ranged from 13.6 to 18.8 microg/mg OVA and 4.8 to 10.3 microg/mg poly(I:C). Murine splenic dendritic cells (DCs) pulsed with PK3-OVA-poly(I:C) microparticles, at antigen doses of 0.01 and 0.1 microg/mL, induced a higher percentage of IFNgamma-producing CD8(+) T cells than DCs treated with PK3-OVA particles or soluble OVA/poly(I:C). A higher antigen dose (1 microg/mL) was less effective, which can be attributed to CTAB toxicity. At the lowest antigen dose (0.01 microg/mL), PK3-OVA-poly(I:C) microparticles also enhanced TNF-alpha and IL-2 production in CD8(+) T cells. These data demonstrate the potential of polyketal microparticles in formulating effective CD8(+) T cell-inducing vaccines comprising protein antigens and dsRNA adjuvants.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Heffernan MJ,Kasturi SP,Yang SC,Pulendran B,Murthy Ndoi
10.1016/j.biomaterials.2008.10.034subject
Has Abstractpub_date
2009-02-01 00:00:00pages
910-8issue
5eissn
0142-9612issn
1878-5905pii
S0142-9612(08)00822-3journal_volume
30pub_type
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