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 prepared from the first N. meningitidis and to express at least one full length meningococcal GNA1870 polypeptide heterologous to the first N. meningitidis;
isolated antigenic vesicles prepared from a second N. meningitidis , wherein the second 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 prepared from the second N. meningitidis and to express at least one full length meningococcal GNA1870 polypeptide heterologous to the second N. meningitidis , wherein the full length meningococcal GNA1870 polypeptides expressed in the first and second N. meningitidis are different; and
a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the isolated antigenic vesicles comprise outer membrane vesicles (OMVs).
3. The composition of claim 1 , wherein the isolated antigenic vesicles comprise microvesicles (MVs).
4. The composition of claim 1 , wherein the isolated antigenic vesicles comprise a mixture of OMVs and MVs.
5. The composition of claim 1 , wherein each of the first and second N. meningitidis is deficient in its capsular polysaccharide.
6. The composition of claim 1 , wherein each of the first and second N. meningitidis is genetically modified to provide for decreased toxic activity of lipid A relative to its parental unmodified N. meningitidis.
7. The composition of claim 1 , wherein each of the first and second N. meningitidis comprises a mutation in a gene involved in biosynthesis or modification of lipid A of its lipopolysaccharide.
8. The composition of claim 1 , wherein the meningococcal GNA1870 polypeptide expressed in the first N. meningitidis is a variant group 1 (v.1) GNA1870 polypeptide.
9. The composition of claim 8 , wherein the meningococcal GNA1870 polypeptide expressed in the second N. meningitides is a variant group 2 (v.2) GNA1870 polypeptide.
10. The composition of claim 9 , wherein each of the first and second N. meningitidis is H44/76.
11. The composition of claim 9 , wherein each of the first and second N. meningitidis is NZ98/254.