Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model

Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Cloucestershire, UK, and one germane isolate. The isolates were all of serotype 15 subtype P1: 7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3, 7, 9 immunotype, when compared to the L1, 8, 10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1, 8, 10 immunotype, established invasive infection, but this was associated with a switch to the L3, 7, 9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3, 7, 9 is associated with invasive disease.