LIVE VACCINE CARRIER STRAINS USEFUL FOR HIGH LEVEL EXPRESSION OF HETEROLOGOUS O-ANTIGENS FROM GRAM-NEGATIVE PATHOGENS AND DERIVATIVES THEREOF FOR USE AS LIVE VACCINES

摘要

The present invention relates to live attenuated gram-negative vaccine carrier strains which are useful for expression and delivery of heterologous O-antigens (O-PS) from gram-negative pathogens. Said strains are deficient in the expression of homologous O-PS due to a defined genetic modification, preferably a deletion, and, thus, capable of efficiently expressing a desired heterologous O-PS in such a way that it is covalently coupled either to homologous or heterologous LPS core lipid A. The present invention furthermore relates to live vaccine carrier strains containing a heterologous gene or a set of heterologous genes encoding O-PS. Preferably, said strains additionally contain genes necessary for the synthesis of complete smooth heterologous LPS. The present invention also relates to live vaccines comprising said strains, preferably for immunization against gram-negative enteric pathogens.