Vaccine against Acinetobacter baumannii based on cellular components deficient in lipopolysaccharide
Inventors
McConnell, Michael James • García Quintanilla, Meritxell • Pulido Toledano, Marina • Pérez Romero, María Pilar • PACHÓN DÍAZ, Jerónimo • INFANTE VIÑOLO, Juan José
Assignees
Fundacion Publica Andaluza Para La Gestion de la Investigacion En Salud De Sevilla • Vaxdyn Sl • Servicio Andaluz de Salud
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Publication Number
US-11160856-B2
Publication Date
2021-11-02
Expiration Date
Abstract
The invention refers to a composition comprising inactivated cells deficient in LPS from the genus Acinetobacter and/or outer membrane vesicles form the same and their use for the manufacture of a medicament, preferably a vaccine, for the prevention of diseases produced by organisms of the genus Acinetobacter.
Core Innovation
The document describes prophylactic/therapeutic vaccination against Acinetobacter baumannii in a mammal using an Acinetobacter baumannii strain deficient in lipopolysaccharide (LPS). LPS deficiency is characterized by partial or complete inactivation of endogenous LPS biosynthesis genes selected from LpxA, LpxC, and LpxD, thereby reducing LPS/endotoxin-associated effects while presenting Acinetobacter baumannii antigens to the immune system.
The invention further encompasses vaccines that include inactivated whole cells and/or outer membrane vesicles (OMVs) that are deficient in LPS via partial or complete inactivation of endogenous LPS biosynthesis genes, including LpxA, LpxB, LpxC, and related genes, with the focus on reduced endotoxin risk and shaping immune responses toward more conserved epitopes.
Optional vaccine compositions include recombinant polypeptides, fusion proteins, and purified outer membrane proteins, including embodiments identified by SEQ ID NOs. Supporting embodiments include selection and characterization of an LPS-deficient derivative IB010 with markedly reduced endotoxin, elicitation of antigen-specific IgG after formalin inactivation, and evaluation of bacterial load, pro-inflammatory cytokines, and survival following challenge, including cross-protection against a clinical isolate.
Claims Coverage
The document provides one independent claim covering a prophylactic method for an infection caused by Acinetobacter baumannii in a mammal, with one dependent refinement claim narrowing the genetic and strain context for LPS deficiency.
Prophylactic administration of an LPS-deficient Acinetobacter baumannii strain
A method for the prophylactic treatment of an infection caused by Acinetobacter baumannii in a mammal, comprising administering an Acinetobacter baumannii strain deficient in lipopolysaccharide (LPS), wherein the LPS deficiency is characterized by partial or complete inactivation of genes selected from LpxA, LpxC and LpxD.
ATCC 19606 LPS deficiency via LpxA/LpxC/LpxD mutations
The prophylactic method of the independent claim, wherein the Acinetobacter baumannii strain is an ATCC 19606 strain having mutations in one or more of the genes selected from LpxA, LpxC and LpxD.
Overall, claim coverage centers on prophylaxis by administering an Acinetobacter baumannii strain with genetically defined LPS deficiency (partial or complete inactivation of LpxA/LpxC/LpxD), with a dependent refinement specifying an ATCC 19606 strain with mutations in one or more of those genes.
Stated Advantages
Reduced endotoxin risk is discussed in connection with LPS-deficient strains and LPS-deficient OMVs.
Immune responses are focused on more conserved epitopes.
The document reports improved survival and reduced post-challenge bacterial loads in challenge evaluations.
The document reports lower pro-inflammatory cytokines.
Documented Applications
Prophylactic treatment of an infection caused by Acinetobacter baumannii in a mammal.
Vaccination using inactivated whole cells and/or outer membrane vesicles (OMVs) that are deficient in lipopolysaccharide (LPS), including an LPS-deficient derivative IB010 and evaluation against challenge including a clinical isolate (Ab-154) for cross-protection.
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