Early T Cell Activation Events In the Context of Single Dose Vaccination with Polyanhydride Nanoparticles

Polyanhydrides based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy) hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) have been shown to enhance protein stability with controlled release, a quality necessary for vaccine antigen delivery. Co-administration of soluble antigen with encapsulated F1-V antigen into polyanhydride nanoparticles leads to prolonged antibody titers of high avidity after a single dose administration that is protective in a Yersinia pestis challenge model at 40 weeks post vaccination. 

Using transgenic T cells from OT I and OT II, in which the T cell receptors are specific for the model antigen ovalbumin (OVA), adoptively transferred into wild type C57BL/6-Thy1.1 recipients, antigen specific T cell expansion and contraction was identified in the secondary lymphoid tissues after vaccination.  Draining lymph nodes and spleens of mice were excised at 1, 3, 5, 7 and 14 days post injection after a single soluble injection of antigen and T cell numbers as well as phenotype were quantified using flow cytometry.  T cell proliferative cytokine IL-2 was also quantified using flow cytometry and ELISpot.

Data from single dose vaccinations with OVA in the transgenic antigen specific T cell (OT I and OT II) adoptive transfer model showed that T cell expansion peaked at 3 days in the draining lymph nodes and contraction of donor T cells follows at the later time points. IL-2 secretion correlates with the peak at 3 days post injection as well.  Current studies aim to explore T cell expansion with the soluble antigen plus encapsulated antigen regimen established in previous work with Y. pestis. We hypothesize that the controlled release and immunostimulatory properties of polyanhydride nanoparticles encapsulating OVA will lead to an extended expansion of T cells in the draining lymph nodes, providing insight into the mechanisms behind the extended antibody titers.