Abstract: The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and Opc, and PorA and OpA and OpC. Alternatively, or in addition, lgtB? is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS in Neisseria vaccine compositions.

Abstract: The present invention relates to immunogenic compositions and vaccines for the prevention or treatment of Gram negative bacterial infection. Immunogenic compositions of the invention comprise transferrin binding protein and Hsf, and the combination of these two antigens have been shown to act synergistically to produce antibodies with high activity in a serum bactericidal assay. This combination of antigens is useful for use in vaccines against Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae.