Immunization with Meningococcal Outer‐Membrane Protein Vesicles Containing Lipooligosaccharide Protects Mice against Lethal Experimental Group BNeisseria meningitidisInfection and Septic Shock

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Abstract
Detergent-treated group B Neisseria meningitidis outer membrane vesicles (D-OMVs) from wild-type M986 and from nonencapsulated mutant M986—non-capsule variant (NCV) were compared as immunogens. Eight weeks after 3 consecutive immunizations with the immunogens, mice were challenged with a lethal dose of purified endotoxin or heat-killed or living N. meningitidis, plus d-galactosamine (400 mg/kg). D-OMVs from M986 induced bactericidal antibodies to both M986 (B:2a:P1.5,2:L3,7) and 6275 (B:2a:P1.2,5:L3) and protected the animals against both strains, whereas D-OMVs from M986-NCV did not protect the animals against infection with 6275 even when high serum bactericidal activity was induced. Tumor necrosis factor—α detected after bacterial infection was high in both protected and unprotected mice; interleukin (IL)—6 was high in mice that died but low in animals that survived. Exogenous administration of recombinant mouse IL-6 reversed the immunogens' protective effects. Protection against infection in mice does not necessarily correlate with the measured levels of serum bactericidal antibody alone, opsonic antibody alone, or cytokine profile alone. A comprehensive assessment of the preclinical efficacy of group B outer-membrane protein vaccines should include monitoring humoral antibodies, cytokine response, and protective effects against lethal infection.

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