Polyanhydride nanovaccine platform enhances antigen-specific cytotoxic T cell responses

Abstract

Polyanhydride nanoparticle-based vaccines (or nanovaccines) stabilize protein antigens, provide sustained antigen release leading to prolonged antigen presence, enhance activation of antigen presenting cells, and elicit protective immunity against respiratory infections upon challenge. However, induction of cell-mediated immunity when mice are immunized with polyanhydride nanovaccines has not been evaluated. Using a transgenic ovalbumin-specific T cell adoptive transfer model, we report the induction of antigen-specific cytotoxic CD8+ T cells expressing an effector memory phenotype by seven days after immunization with nanovaccine formulations. Furthermore, mice immunized with polyanhydride nanovaccines demonstrated enhanced recall responses after antigen re-exposure 35 days post-immunization indicating the activation and recruitment of antigen-specific memory CD8+ T cells to the site of antigen deposition.

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

“…1, the particle morphology and size of the functionalized particles were similar to previously reported data (6,19,28,48,49). The characterization of polyanhydride nanoparticles before and after surface modification was consistent with previous studies (6,17,18).…”

“…Polyanhydride nanoparticles have displayed these characteristics in both in vitro and/or in vivo settings (6,9,(14)(15)(16)(17)(18)(19)(20). In particular, the use of biodegradable nanoparticles for lung delivery is an attractive proposition because of the following advantages: (1) uniform particle distribution in the lung, (2) local administration of vaccine antigens or therapeutic drugs, (3) sustained delivery of macromolecules, (4) improved patient compliance associated with noninvasive immunization and administration of fewer doses, and (5) avoidance of first-pass metabolism, among others (2,12,(21)(22)(23).…”

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

“…Previous work with polyanhydride nanovaccines indicated expansion of antigen-specific CD8 + T cells following nanovaccine immunization, resulting in memory T cell populations that responded to antigenexpressing tumor challenge (CD8 + T cells). 17 This broad repertoire of immune responses induced by polyanhydride nanovaccines may prove beneficial for influenza vaccine efficacy because robust cell-mediated responses are often associated with broader protective immunity and directed at conserved epitopes. 18,19 Previously, soluble H5 HA trimers (sH5 3 ) from H5N1 influenza virus A/Whooper Swan/Mongolia/244/05 were produced using a baculovirus insect cell expression system and shown to maintain their oligomeric structure and antigenicity upon release from polyanhydride nanoparticles.…”

The effect of polyanhydride chemistry in particle-based cancer vaccines on the magnitude of the anti-tumor immune response

“…Furthermore, since polyanhydrides are inert and their degradation products are safe, they have high biocompatibility and are suitable for in vivo drug/antigen delivery [24]. Additionally, polyanhydrides have been reported to have inherent adjuvant properties and polyanhydride particles can act as Toll-like receptor (TLR) agonists on various TLRs including TLRs 2, 4, and 5 [19, 20, 36–47]. …”