Importance of Antibodies to Lipopolysaccharide in Natural and Vaccine-Induced Serum Bactericidal Activity against Neisseria meningitidis Group B

Abstract

Analysis of the specificity of bactericidal antibodies in normal, convalescent, and postvaccination human sera is important in understanding human immunity to meningococcal infections and can aid in the design of an effective group B vaccine. A collection of human sera, including group C and group B convalescent-phase sera, normal sera with naturally occurring cross-reactive bactericidal activity, and some postvaccination sera, was analyzed to determine the specificity of cross-reactive bactericidal antibodies. Analysis of human sera using a bactericidal antibody depletion assay demonstrated that a significant portion of the bactericidal activity could be removed by purified lipopolysaccharide (LPS). LPS homologous to that expressed on the bactericidal test strain was most effective, but partial depletion by heterologous LPS suggested the presence of antibodies with various degrees of cross-reactivity. Binding of anti-L3,7 LPS bactericidal antibodies was affected by modification of the core structure, suggesting that these functional antibodies recognized epitopes consisting of both core structures and lacto-N-neotetraose (LNnT). When the target strain was grown with 5-cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA) to increase LPS sialylation, convalescentphase serum bactericidal titers were decreased by only 2-to 4-fold, and most remaining bactericidal activity was still depleted by LPS. Highly sialylated LPS was ineffective in depleting bactericidal antibodies. We conclude that natural infections caused by strains expressing L3,7 LPS induce persistent, protective bactericidal antibodies and appear to be directed against nonsialylated bacterial epitopes. Additionally, subsets of these bactericidal antibodies are cross-reactive, binding to several different LPS immunotypes, which is a useful characteristic for an effective group B meningococcal vaccine antigen.

The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C

“…In previous studies, adults immunized with OMV vaccines showed SBA responses to strains with heterologous PorA VR sequence types to the vaccines [6]. The responsible OMV antigens were not defined but may include OpA (referred to as class 5 protein)[23, 24] and LOS [25]. …”

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection againstNeisseria gonorrhoeae

“…We also examined the reactivity of the immune serum against Ng lipooligosaccharide (LOS) based on the report that a significant percentage of the bactericidal activity induced by an Nm OMV vaccine was directed towards Nm LOS [32]. Neisserial LOS is a branched structure that consists of oligosaccharide extensions from the core oligosaccharide called the α- and β-chains.…”

Effect of fresh frozen plasma on the in vitro activation of U937 monocytes: a potential role for the age of blood donors and their underlying cytokine profile

“…The final effect of these soluble receptors may be the interference in cellular actions, altering the production of other cytokines. Alternatively, serum IgM and IgG anti-LPS antibodies have already been demonstrated in Balb/c mice treated with LPS, and anti-LPS antibodies with antibacterial activity were recently described in humans [ 34 , 35 ].…”