GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by

1. A composition comprising:

isolated antigenic outer membrane vesicles (OMVs), microvesicles (MVs), or a mixture of the OMVs and the MVs, wherein the OMVs or the MVs are prepared from a first Neisseria meningitidis that is genetically modified:

(a) to comprise a mutation in a gene involved in biosynthesis or modification of lipid A of its lipopolysaccharide and

(b) to overexpress a meningococcal GNA1870 polypeptide, wherein the overexpression consists of the overexpression of a full-length meningococcal GNA1870 polypeptide in the OMVs or the MVs at a level that is greater than three to ten times the level of the endogenous GNA1870 polypeptide expressed by unmodified parental Neisseria meningitidis from which the genetically modified first Neisseria meningitidis is obtained,

wherein the OMVs or the MVs are prepared without using a detergent,

and wherein the composition, when administered to a mammalian subject, elicits serum antibodies specific to the overexpressed GNA1870 polypeptide that are bactericidal against at least three Neisseria meningitidis strains that express a GNA1870 polypeptide and a heterologous meningococcal PorA protein, and

a pharmaceutically acceptable carrier.

2. The composition of claim 1 , wherein the isolated antigenic vesicles are a mixture of the OMVs and the MVs.

3. The composition of claim 1 , wherein the genetically modified first Neisseria meningitidis is obtained from Neisseria meningitidis strain H44/76.

4. The composition of claim 1 , wherein the first Neisseria meningitidis is genetically modified to overexpress the GNA1870 polypeptide from a heterologous promoter.

5. The composition of claim 1 , wherein the Neisseria meningitidis is deficient in capsular polysaccharide.

6. The composition of claim 1 , the composition further comprises:

isolated antigenic outer membrane vesicles (OMVs) or microvesicles (MVs) prepared from a second Neisseria meningitidis that is genetically modified to overexpress a meningococcal GNA1870 polypeptide, wherein the overexpression consists of the overexpression of a heterologous full-length meningococcal GNA1870 polypeptide in the OMVs or the MVs at a level that is greater than three times the level of the endogenous GNA1870 polypeptide expressed by unmodified parental Neisseria meningitidis from which the second genetically modified Neisseria meningitidis is obtained, wherein the OMVs or the MVs are prepared without using a detergent, and the composition when administered to a mammalian subject, elicits serum antibodies specific to the GNA1870 polypeptide overexpressed by the second genetically modified Neisseria meningitidis and wherein the antibodies are bactericidal against at least three Neisseria meningitidis strains that express a GNA1870 polypeptide and a heterologous meningococcal PorA protein, wherein the second Neisseria meningitidis is genetically diverse to the first Neisseria meningitidis.

7. The composition of claim 6 , wherein the first and the second Neisseria meningitidis are genetically diverse in that the two Neisseria meningitidis differ in at least one of serogroup, serotype, or subserotype.

8. The composition of claim 6 , wherein the GNA1870 polypeptide overexpressed in the second Neisseria meningitidis is different from the GNA1870 polypeptide overexpressed in the first Neisseria meningitidis.

9. The composition of claim 1 , wherein the first Neisseria meningitidis is genetically modified to overexpress at least two different meningococcal GNA1870 polypeptides of different variant groups.

10. The composition of claim 1 , wherein the first Neisseria meningitidis is genetically modified to disrupt the production of the endogenous GNA1870 polypeptide.

11. The composition of claim 6 , wherein the second Neisseria meningitidis is genetically modified to disrupt the production of the endogenous GNA1870 polypeptide.

12. The composition of claim 1 , wherein the Neisseria meningitidis is of serogroup B.

13. The composition of claim 6 , wherein the Neisseria meningitidis is of serogroup B.

14. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is four or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

15. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is five or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

16. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is six or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

17. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is seven or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

18. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is eight or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

19. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is nine or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

20. The composition of claim 1 , wherein the overexpressed GNA1870 polypeptide is overexpressed at a level that is ten or more times greater than the level of the endogenous GNA1870 polypeptide expressed by the unmodified parental Neisseria meningitidis from which the first genetically modified Neisseria meningitidis is obtained.

21. A method of producing the composition of claim 1 , the method comprising:

culturing the genetically modified first Neisseria meningitidis;

preparing the OMVs or the MVs from the culture; and

combining the OMVs or the MVs with the pharmaceutically acceptable carrier to produce the composition.

22. A method of producing the composition of claim 2 , wherein the method comprises mixing the OMVs and the MVs to produce the mixture of the OMVs and the MVs.

23. A method of producing the composition of claim 4 , the method comprising:

culturing the genetically modified first Neisseria meningitidis;

preparing the OMVs or the MVs from the culture; and

combining the OMVs or the MVs with the pharmaceutically acceptable carrier to produce the composition.

24. A method of producing the composition of claim 9 , the method comprising:

culturing the genetically modified first Neisseria meningitidis;

preparing the OMVs or the MVs from the culture; and

combining the OMVs or the MVs with the pharmaceutically acceptable carrier to produce the composition.

25. A method of producing the composition of claim 5 , the method comprising:

culturing the genetically modified first Neisseria meningitidis;

preparing the OMVs or the MVs from the cultures; and

combining the OMVs or the MVs with the pharmaceutically acceptable carrier to produce the composition.

26. A method of eliciting a bactericidal immune response against Neisseria meningitidis in a mammalian subject, the method comprising administering to the mammalian subject an immunologically effective amount of the composition of claim 1 .

27. The method of claim 26 , wherein the first Neisseria meningitidis is Neisseria meningitidis of serogroup B.

28. The method of claim 27 , wherein the first Neisseria meningitidis is Neisseria meningitidis H44/76.

29. The method of claim 26 , wherein the first Neisseria meningitidis is genetically modified to overexpress the GNA1870 polypeptide from a heterologous promoter.

30. The method of claim 26 , wherein the first Neisseria meningitidis is genetically modified to overexpress at least two different meningococcal GNA1870 polypeptides of different variant groups.

31. A method of eliciting a bactericidal immune response against Neisseria meningitidis in a mammalian subject, the method comprising administering to the mammalian subject an immunologically effective amount of the composition of claim 6 .

32. The method of claim 31 , wherein the GNA1870 polypeptide overexpressed in the second genetically modified Neisseria meningitidis is different from the GNA1870 polypeptide overexpressed in the first genetically modified Neisseria meningitidis.