Lipid A mimetics are potent adjuvants for an intranasal pneumonic plague vaccine.

Vaccine
Christina L AirhartScott A Minnich

Abstract

An effective intranasal (i.n.) vaccine against pneumonic plague was developed. The formulation employed two synthetic lipid A mimetics as adjuvant combined with Yersinia pestis-derived V- and F1-protective antigens. The two nontoxic lipid A mimetics, classed as amino-alkyl glucosaminide 4-phosphates (AGPs) are potent ligands for the Toll-like receptor (TLR) 4. Using a murine (BALB/c) pneumonic plague model, we showed a single i.n. application of the vaccine provided 63% protection within 21 days against a Y. pestis CO92 100 LD50 challenge. Protection reached 100% by 150 days. Using a homologous i.n. 1 degrees /2 degrees dose regimen, with the boost administered at varying times, 63% protection was achieved within 7 days and 100% protection was achieved by 21 days after the first immunization. Little or no protection was observed in animals that received antigens alone, and no protection was observed when the vaccine was administered to BALB/c TLR4 mutant mice. Vaccine-induced serum IgG titers to F1 and V-antigen were reflected in high titers for IgG1 and IgG2a, the latter reflecting a bias for a cell-mediated (TH1) immune response. This intranasal vaccine showed 90% protection in Sprague-Dawley rats challenged with 1000 LD50. W...Continue Reading

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Citations

Jun 15, 2011·Applied Microbiology and Biotechnology·Jason A RosenzweigAshok K Chopra
Feb 18, 2012·Science Signaling·William S BowenJay T Evans
Nov 5, 2010·Journal of Drug Targeting·Inderjit Jabbal-Gill
Feb 23, 2012·Scientific Reports·Bret D UleryBalaji Narasimhan
Dec 27, 2016·Frontiers in Immunology·Shailendra Kumar Verma, Urmil Tuteja
Sep 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Courtney E ChandlerRobert K Ernst

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