Lipid a deficient mutants of
View Patent ↗The invention provides lipid A deficient mutant Neisseria meningitidis cells, pharmaceutical compositions incorporating such cells, and methods of using such cells.
1. A method of eliciting an immune response in a subject against Neisseria meningitidis comprising administering to the subject a pharmaceutical composition comprising
(a) a Neisseria meningitidis cell comprising a disrupted msbB gene, wherein the cell has a reduced amount of lipooligosaccharide (LOS) present in the cell's outer membrane and/or lipid A components present in the cell's outer membrane as compared to the corresponding wild-type Neisseria meningitidis cell, wherein the msbB gene is disrupted by mutagenesis, wherein the cell is Neisseria meningitidis NMBA11K3 cell having ATCC designation PTA-7257 or its acapsular mutant NMBA11K3cap-; and
(b) a pharmaceutically acceptable carrier, wherein the composition is capable of eliciting an immune response against Neisseria meningitidis.
2. The method of claim 1 , wherein the pharmaceutical composition is administered orally, mucosally or by subcutaneous or intramuscular injection.
3. The method of claim 1 , wherein the msbB gene is disrupted by mutagenesis.
4. The method of claim 3 , wherein the mutagenesis is a deletion, insertion or substitution mutagenesis, or a combination thereof.
5. The method of claim 1 , wherein the cell has a reduced amount of the LOS in its outer membrane as compared to the corresponding wild-type Neisseria meningitidis cell.
6. The method of claim 1 , wherein the cell has a reduced amount of the lipid A components present in the cell's outer membrane as compared to the corresponding wild-type Neisseria meningitidis cell.
7. The method of claim 1 , wherein the cell has reduced toxicity as compared to the corresponding wild-type Neisseria meningitidis cell.
8. The method of claim 1 , wherein the cell is the Neisseria meningitidis NMBA11K3 cell having ATCC designation PTA-7257.