Methods, compositions and vaccines relating to
The invention provides compositions and methods for screening subjects at risk for contracting meningococcal disease and/or at risk for failing to elicit an immunogenic response to a vaccine against Neisseria meningitidis . The invention also provides kits for carrying out these screens, and improved vaccines against Neisseria meningitidis.
1. A mutant Neisseria meningitidis that lacks one or more polypeptide sequences that specifically bind to a Neisseria meningitidis blocking antibody, wherein said one or more polypeptide sequences are selected from the group consisting of
a) H.8 polypeptide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and
b) H.8 polypeptide sequence that lacks one or more H.8 portions selected from the group consisting of:
1) from amino acids 18 to 98 of SEQ ID NO: 1,
2) from amino acids 18 to 93 of SEQ ID NO: 2, and
3) from amino acids 18 to 98 of SEQ ID NO: 3.
2. The mutant of claim 1 , wherein said mutant
i) lacks said H.8 polypeptide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and
ii) comprises a deletion of Laz polypeptide that specifically binds to said Neisseria meningitidis blocking antibody, wherein said Laz polypeptide is selected from the group consisting of SEQ ID NO:5, SEQ ID NO: 6, and SEQ ID NO: 7.
3. The mutant of claim 1 , wherein said mutant
i) lacks said H.8 polypeptide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and
ii) comprises a Laz polypeptide that lacks one or more Laz portions, wherein said one or more Laz portions specifically bind to said Neisseria meningitidis blocking antibody and are selected from the group consisting of
1) at least one repeat of AAEAP (SEQ ID NO: 10),
2) from amino acids 18 to 61 of SEQ ID NO: 5,
3) from amino acids 18 to 61 of SEQ ID NO: 6, and
4) from amino acids 18 to 61 of SEQ ID NO: 7.
4. The mutant of claim 1 , wherein said mutant
i) comprises said H.8 polypeptide sequence that lacks the one or more H.8 portions, and
ii) comprises a deletion of Laz polypeptide that specifically binds to said Neisseria meningitidis blocking antibody, wherein said Laz polypeptide is selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7.
5. The mutant of claim 1 , wherein said mutant
i) comprises said H.8 polypeptide sequence that lacks the one or more H.8 portions, and
ii) comprises a Laz polypeptide that lacks one or more Laz portions, wherein said one or more Laz portions specifically bind to said Neisseria meningitidis blocking antibody and are selected from the group consisting of
1) at least one repeat of AAEAP (SEQ ID NO: 10),
2) from amino acids 18 to 61 of SEQ ID NO: 5,
3) from amino acids 18 to 61 of SEQ ID NO: 6, and
4) from amino acids 18 to 61 of SEQ ID NO: 7.
6. The mutant of claim 1 , wherein said mutant lacks said H.8 polypeptide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3.
7. A mutant Neisseria meningitidis that comprises a mutant H.8 polypeptide, wherein said mutant H.8 polypeptide lacks the H.8 portion from amino acids 18 to 98 of SEQ ID NO: 1.
8. A composition comprising an outer membrane vesicle (OMV) prepared from the mutant Neisseria meningitidis of claim 1 .