Immunochemical characterization of an Ogawa-Inaba common antigenic determinant of Vibrio cholerae O1

Abstract

Cholera remains an important public health problem in many parts of the world and the availability of an effective cholera vaccine is important for the prevention of cholera in the countries affected by this disease. Despite the apearance in 1992 of a new serogroup, O139, of Vibrio cholerae, most of the cholera outbreaks are still caused by V. cholerae O1 biotype El Tor. Vaccine trials in Asia from 1968 to 1971, and studies of the production of serotypespecific antiserum in rabbits and of the protective activity of monoclonal antibodies against diarrhoeal disease in neonatal mice, have led to the conclusion that the Ogawa serotype contains a specific antigenic determinant whereas the Inaba serotype contains a different antigenic determinant that cross-reacts with the Ogawa serotype. By studying the binding of anti-Ogawa monoclonal antibodies to synthetic oligosaccharide fragments mimicking the Ogawa O-specific polysaccharide, it has been shown that the terminal monosaccharide, bearing the 2-O-methyl group in the O-specific polysaccharide, is most probably the serotype-specific determinant for the Ogawa strain. However, study of the binding of a monoclonal antibody recognizing both Ogawa and Inaba serotypes suggested partial recognition of the core as well as of the O-specific polysaccharide of the LPS of V. cholerae O1. To further characterize this antigenic determinant that is common to the Ogawa and Inaba serotypes, the core and the O-specific polysaccharide linked to the core of V. cholerae O1 LPS were purified by preparative electrophoresis. The O-specific polysaccharide linked to the core was subjected to periodate oxidation to destroy sugars from the core. Binding studies of these purified saccharide fragments to a monoclonal antibody which is protective in mice and specific to the antigenic determinant common to Ogawa and Inaba serotypes showed that both the core and the O-specific polysaccharide are involved in this common antigenic determinant. This explains how the presence or the absence of the Ogawa-specific antigenic determinant would lead to the expression of two independent antigenic determinants of V. cholerae O1, one specific to the Ogawa serotype and the other common to both Ogawa and Inaba serotypes.

Crystal structure of an anti-carbohydrate antibody directed againstVibrio choleraeO1 in complex with antigen: Molecular basis for serotype specificity

“…1a). As shown by this and previous work (8,37), Abs specific for the terminal perosamine could selectively protect against the Ogawa serotype but would fail to recognize the Inaba serotype. Therefore, protective Abs against both serotypes should bind to the inner part of the O-SP and͞or to sugar residues defining the core of the LPS molecule.…”

“…The LPS of the Inaba serotype possesses internal structural units common to both Ogawa and Inaba serotypes (35,36), and it has been proposed that both the core and the O-SP (see Fig. 1a) may be involved in this common epitope (37). The crystal structure of the cavity type mAb S-20-4 reported herein confirms the serotype specificity of this and related anti-Ogawa Abs by showing the pivotal contribution by so small a structural fragment in the antigenic determinant as a methyl group.…”

Edible ice in Jakarta, Indonesia, is contaminated with multidrug-resistant Vibrio cholerae with virulence potential

“…Serogroup O1 is divided into two major serotypes, Ogawa and Inaba (Stroeher et al 1992). These serotypes differ by their terminal monosaccharides (Villeneuve et al, 1999). V. cholerae O1 Ogawa has been responsible for causing frequent diarrhoeal outbreaks over the last 10 years, although Inaba is becoming increasingly associated with cholera outbreaks (Chhotray et al, 2002).…”

Characterization of a novel protective monoclonal antibody that recognizes an epitope common to Vibrio cholerae Ogawa and Inaba serotypes

“…However, the variable heavy chain of mAb I-24-2 differs extensively from those of 72.1 and ZAC-3. Previous studies have suggested that, while mAb ZAC-3 recognizes an epitope at the lipid A or core region, mAb I-24-2 recognizes an epitope at the junction of the core and O-SP region (Lullau et al, 1996;Villeneuve et al, 1999;Wang et al, 1998 In an attempt to determine if the protective epitope that is common to both Ogawa and Inaba serotype LPS can be utilized in a subunit vaccine against cholera, peptide mimics of this epitope were identified by screening phage display libraries with mAb 72.1. Eleven cyclic peptide mimics constrained by two cysteines were identified from three different phage display libraries.…”

“…The protective efficacy of ZAC-3 has not been reported. Inhibition studies revealed that the binding of I-24-2 to Ogawa and Inaba LPS may be mediated by a region located at the junction of the O-SP and core region of the LPS (Villeneuve et al, 1999;Wang et al, 1998). The ZAC-3 mAb binds to an epitope in the lipid A or core region but not to the O-SP (Lullau et al, 1996).…”