Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D-binding outer membrane protein and the ubiquitous surface proteins A1 and A2

TY - JOUR

T1 - Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D-binding outer membrane protein and the ubiquitous surface proteins A1 and A2

AU - Tan, Thuan Tong

AU - Christensen, Jens Jørgen

AU - Dziegiel, Morten Hanefeld

AU - Forsgren, Arne

AU - Riesbeck, Kristian

PY - 2006/11

Y1 - 2006/11

N2 - Moraxella catarrhalis immunoglobulin D-binding protein (MID) is a complex antigen with unique immunoglobulin D (IgD)-binding, adhesion, and hemagglutination properties. Previous studies have shown that antibodies raised against MID764-913 in rabbits inhibited M. catarrhalis adhesion to human alveolar epithelial cells, and immunization with MID764-913 resulted in an increased pulmonary clearance in a murine model. Strong immune responses against MID have also consistently been shown in humans. Here, the MID-specified IgG responses were compared to those of ubiquitous surface proteins A1 and A2 (UspA1/A2) using a series of recombinant fragments that spanned all three proteins. Sera were obtained from young children, aged 6 months to 1 year (n=8) and 2 to 3 years (n=15), and healthy adults (n=16). Acute- and convalescent-phase sera from chronic obstructive pulmonary disease (COPD) patients with M. catarrhalis infective exacerbations (n=23) were also analyzed. Young children, who are at risk of M. catarrhalis infection, had low levels of anti-MID and anti-UspA1/A2 antibodies. Healthy adults and the majority of COPD patients (16/23) had high levels of antibodies directed against, among others, the adhesive domain of MID and the fibronectin- and C3-binding domains of UspA1/A2. Among eight COPD patients in whom a rise in antibody levels could be detected, these functional domains were also the main regions targeted by the antibodies. In addition, human IgG directed against MID was bactericidal and anti-MID antibodies were additive to antibodies targeting UspA1/A2. Hence, the functional domains in these three antigens may have significant potential in a future vaccine against M. catarrhalis.

AB - Moraxella catarrhalis immunoglobulin D-binding protein (MID) is a complex antigen with unique immunoglobulin D (IgD)-binding, adhesion, and hemagglutination properties. Previous studies have shown that antibodies raised against MID764-913 in rabbits inhibited M. catarrhalis adhesion to human alveolar epithelial cells, and immunization with MID764-913 resulted in an increased pulmonary clearance in a murine model. Strong immune responses against MID have also consistently been shown in humans. Here, the MID-specified IgG responses were compared to those of ubiquitous surface proteins A1 and A2 (UspA1/A2) using a series of recombinant fragments that spanned all three proteins. Sera were obtained from young children, aged 6 months to 1 year (n=8) and 2 to 3 years (n=15), and healthy adults (n=16). Acute- and convalescent-phase sera from chronic obstructive pulmonary disease (COPD) patients with M. catarrhalis infective exacerbations (n=23) were also analyzed. Young children, who are at risk of M. catarrhalis infection, had low levels of anti-MID and anti-UspA1/A2 antibodies. Healthy adults and the majority of COPD patients (16/23) had high levels of antibodies directed against, among others, the adhesive domain of MID and the fibronectin- and C3-binding domains of UspA1/A2. Among eight COPD patients in whom a rise in antibody levels could be detected, these functional domains were also the main regions targeted by the antibodies. In addition, human IgG directed against MID was bactericidal and anti-MID antibodies were additive to antibodies targeting UspA1/A2. Hence, the functional domains in these three antigens may have significant potential in a future vaccine against M. catarrhalis.

KW - Adult

KW - Antigens, Bacterial

KW - Bacterial Outer Membrane Proteins

KW - Bacterial Proteins

KW - Child, Preschool

KW - Humans

KW - Immunoglobulin D

KW - Immunoglobulin G

KW - Infant

KW - Moraxella (Branhamella) catarrhalis

KW - Phosphoric Diester Hydrolases

KW - Pulmonary Disease, Chronic Obstructive

U2 - 10.1128/IAI.00702-06

DO - 10.1128/IAI.00702-06

M3 - Journal article

C2 - 16966403

SN - 0019-9567

VL - 74

SP - 6377

EP - 6386

JO - Infection and Immunity

JF - Infection and Immunity

IS - 11

ER -