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 Neisseria meningitidis ( N. meningitidis ), wherein the 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 a vesicle prepared from the N. meningitidis and overexpress at least one full length meningococcal GNA1870 polypeptide so as to produce a level of the overexpressed GNA1870 polypeptide sufficient to provide for production of the isolated antigenic vesicles that, when administered to a mammalian subject, elicit anti-meningococcal GNA1870 polypeptide antibodies, wherein the overexpressed GNA1870 polypeptide is a variant 1 or a variant 2 meningococcal GNA1870 polypeptide heterologous to the N. meningitidis,
wherein the isolated antigenic vesicles are outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of the OMVs and the MVs, and
wherein the N. meningitidis is genetically modified to provide for decreased toxic activity of its lipid A relative to its parental unmodified N. meningitidis ; and
a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the N. meningitidis is genetically modified to provide for expression of the overexpressed meningococcal GNA1870 polypeptide from a heterologous promoter.
3. The composition of claim 1 , wherein the N. meningitidis is deficient in its capsular polysaccharide.
4. The composition of claim 1 , wherein the N. meningitidis comprises a mutation in a gene involved in biosynthesis or modification of lipid A of its lipopolysaccharide.
5. The composition of claim 1 , wherein the isolated antigenic vesicles are prepared without using a detergent.
6. The composition of claim 1 , wherein the N. meningitidis is genetically modified to produce at least two different full length meningococcal GNA1870 polypeptides.
7. The composition of claim 1 , wherein the N. meningitidis is H44/76 or NZ98/254.
8. A Neisseria meningitidis ( N. meningitidis ) that is genetically modified to disrupt production of the endogenous GNA1870 polypeptide so that the endogenous GNA1870 is not present at detectable levels in antigenic vesicles isolated from the N. meningitidis and to overexpress at least one full length meningococcal GNA1870 polypeptide so as to produce a level of the overexpressed GNA1870 polypeptide sufficient to provide for production of the isolated antigenic vesicles that, when administered to a mammalian subject, elicit anti-meningococcal GNA1870 polypeptide antibodies, wherein the overexpressed GNA1870 polypeptide is a variant 1 or a variant 2 meningococcal GNA1870 polypeptide heterologous to the N. meningitidis , and wherein the antigenic vesicles are outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of the OMVs and the MVs.
9. The N. meningitidis of claim 8 , wherein the N. meningitidis is H44/76 or NZ98/254.
10. The N. meningitidis of claim 8 , wherein the N. meningitidis is genetically modified to provide for no detectable toxic activity of lipid A.
11. The N. meningitidis of claim 8 , wherein the overexpressed GNA1870 polypeptide is a variant 1 meningococcal GNA1870 polypeptide.
12. The N. meningitidis of claim 8 , wherein the overexpressed GNA1870 polypeptide is a variant 2 meningococcal GNA1870 polypeptide.