GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by
View Patent ↗The present invention generally provides methods and compositions for eliciting an immune response against Neisseria spp. bacteria in a subject, particularly against a Neisseria meningitidis serogroup B strain.
1. A composition comprising:
isolated antigenic vesicles prepared from a first Neisseria meningitidis ( N. meningitidis ),
wherein the first N. meningitidis is genetically modified to disrupt production of the endogenous GNA1870 polypeptide so that the endogenous GNA1870 is not present at detectable levels in the isolated antigenic vesicles and to express at least one heterologous full length meningococcal GNA1870 polypeptide; and
a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the isolated antigenic vesicles are outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of OMVs and MVs.
3. The composition of claim 1 , wherein the first N. meningitidis is genetically modified to provide for expression of the heterologous meningococcal GNA1870 polypeptide from a heterologous promoter.
4. The composition of claim 1 , wherein the first N. meningitidis is deficient in its capsular polysaccharide.
5. The composition of claim 1 , wherein the first N. meningitidis is genetically modified to provide for no detectable toxic activity of lipid A.
6. The composition of claim 1 , wherein the first N. meningitidis comprises a mutation in a gene involved in biosynthesis or modification of lipid A of its lipopolysaccharide.
7. The composition of claim 1 , wherein the isolated antigenic vesicles are prepared without using a detergent.
8. The composition of claim 1 , wherein the first N. meningitidis is genetically modified to produce at least two different heterologous full length meningococcal GNA1870 polypeptides.
9. The composition of claim 8 , wherein the heterologous GNA1870 polypeptides are of different meningococcal GNA1870 polypeptide variant groups, wherein the variant groups are v.1, v.2 and v.3.
10. The composition of claim 1 , wherein the first N. meningitidis is H44/76.
11. The composition of claim 1 , wherein the composition further comprises:
an isolated antigenic vesicle prepared from a second N. meningitidis , wherein the second N. meningitidis is genetically modified to express a heterologous full length meningococcal GNA1870 polypeptide, and wherein the second N. meningitidis is genetically diverse to the first N. meningitidis.
12. The composition of claim 11 , wherein the first and the second N. meningitidis are genetically diverse in that they differ in at least one of serogroup, serotype, or serosubtype.
13. The composition of claim 11 , wherein the GNA1870 polypeptide of the second N. meningitidis is different from the heterologous GNA1870 polypeptide expressed in the first N. meningitidis.
14. The composition of claim 11 , wherein the GNA1870 polypeptide expressed in the first N. meningitidis is of a different GNA1870 polypeptide variant group than that of the second N. meningitidis , and the first and the second N. meningitidis produce different meningococcal PorA polypeptides.
15. The composition of claim 11 , wherein the second N. meningitidis is genetically modified to disrupt production of an endogenous GNA1870 polypeptide.
16. The composition of claim 11 , wherein the heterologous GNA1870 polypeptide expressed in the first and the second N. meningitidis are of different variant groups.
17. A method of producing the composition of claim 1 , the method comprising:
culturing the first N. meningitidis;
preparing the isolated antigenic vesicles from the cultured first N. meningitidis ; and
combining the antigenic vesicles with a pharmaceutically acceptable carrier to produce the composition.
18. The method of claim 17 , wherein the first N. meningitidis is genetically modified to produce at least two different heterologous full length meningococcal GNA1870 polypeptides.
19. A method of eliciting an immune response against a N. meningitidis in a mammalian subject, the method comprising administering to the mammalian subject an immunologically effective amount of the composition of claim 1 .