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DARPA 7-Day Challenge

机译：DaRpa 7天挑战赛

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摘要

For many diseases conferring rapid protection against an intracellular pathogen is required to prevent pathogen related death. To this end, we have developed a microparticulate vaccine carrier comprised of the novel polymer, acetalated dextran (Ac-DEX). Ac-DEX is an aptly designed polymer for vaccine applications because it s base material is FDA approved dextran and it has acid sensitivity for triggered release inside the phagosome, tunable degradation that can range from hours to months, and enhanced MHC I & II presentation with subunit antigen, compared to other biomaterials. In microparticulate form it can be used to passively target dendritic cells through size exclusion. We have formulated particles encapsulating recombinant protective antigen (rPA) or lysate (Francisella novicida, Burkholderia pseudomallei strain 1026) and the TLR 7/8 agonist resiquimod. Vaccination at 0 and 7 days (sub-Q) results in high levels of antigen specific antibodies for encapsulated formulations, compared to rPA + alum. Additionally, A/J mice (n=10) were aggressively challenged intratracheally with Bacillus anthracis (Sterne Strain) on day 14, 21 and 28, with survival in groups with encapsulated and/or free rPA and resiquimod. Studies were also performed with Ac-DEX microparticles encapsulating F. novicida or B. pseudomallei lysate. Balb/C (n=10 for F. novicida and n=25 for B. pseudomallei) mice were vaccinated on 0 and 7 days (sub-Q) with i.p. challenge on day 14. For the B. pseudomallei evaluation, we had delay onset to death in several groups, with post-mortem liver, spleen and blood in three of the nine experimental groups. Overall we have shown the efficacy of Ac-DEX microparticles for rapid vaccination against two intracellular bacterial pathogens.

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