Live self-destructing bacterial adjuvants to enhance induction of immunity
AssigneeUniversity of Florida Research Foundation, Inc.
InventorRoy Curtiss
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Abstract
Disclosed herein are unique adjuvant compositions comprising an attenuated derivative of a self-destructing bacterial pathogen that undergoes lysis in vivo. In exemplary embodiments, the bacterial pathogen is a Salmonella spp. Also disclosed are methods for enhancing an immune response using the adjuvants disclosed herein.
Claims13
An adjuvant for the enhancement of vaccine efficacy, the adjuvant comprising an attenuated derivative of a bacterial pathogen that undergoes lysis in vivo, wherein the adjuvant comprises an attenuated Salmonella typhimurium (S. typhimurium) bacterium, comprising (a) one or more mutations facilitating lysis in vivo, comprising (i) ΔPmurA::TT rhaRS PrhaBAD murA, and/or (ii) a combination of ΔPasdA::TT araC ParaBAD asdA or ΔPasdA::TT rhaRS PrhaBAD asdA, Δalr, and ΔPdadB::TT rhaRS PrhaBAD dadB;
- and, optionally, a combination of (a) with (b) or (c), wherein (b) is one or more mutations to enhance recruitment of innate immunity comprising (i) ΔpagP::Plpp lpxE and/or ΔlpxR::Plpp lpxF, (ii) ΔpagL or ΔpagP or (iii) ΔlpxR, ΔarnT, ΔeptA, ΔwaaC, ΔwaaG, ΔwaaL, ΔwbaP, Δpmi or Δrfc or a combination thereof;
- or (iv) ΔPstc::PmurA stc and ΔstcABCD or ΔPsaf::PmurA saf and ΔsafABCD, or a combination thereof, and wherein (c) is a mutation enhancing safety and effective immunogenicity, comprising ΔsifA, ΔsopF, ΔrecA or ΔsopB.
Dependencies are inferred from the claim text.