The immunogenicity of the liposome-associated outer membrane proteins (OMPs) of Moraxella catarrhalis

Abstract

The outer membrane proteins (OMPs) are the most immunogenic and attractive of the Moraxella catarrhalis vaccine antigens that may induce the protective immune response. The aim of this study was to determine the effectiveness of two types of OMP-associated phosphatidylcholine (PC) liposomal formulations (OMPs-PC, PC-OMPs) and of Zwittergent-based proteomicelles (OMPs-Z) in potentiating an anti-OMP systemic immune response in mice. The immunogenicities of the above preparations were evaluated by assessing serum anti-OMP IgG and IgA reactivity in the post-immunized mouse antisera using ELISA and Western blotting. Additionally, the cross-reactivity of the most effective anti-OMP response was determined using heterologous sera from both humans and mice. Both the proteoliposomes and the proteomicelles showed high immunogenic properties and did not elicit any distinct quantitative differences in the antibody titer or qualitative differences in the pattern of the mouse antisera. The post-immunized mouse antisera predominantly recognized a ∼60-kDa OMP of M. catarrhalis. That protein was also found to be a highly cross-reactive antigen interacting with a panel of pooled mouse antisera produced by immunization either with whole cells or the purified OMPs of heterologous M. catarrhalis strains. Furthermore, normal sera collected from healthy children were found to be preferentially reactive with the 60-kDa OMP. The serum-specific IgG, IgA and IgM were respectively detected via immunoblotting in 90%, 85% and 30% of heterologous human sera. This similar immunogenic effectiveness of both OMP-associated liposomal formulations could contribute to the practical use of such formulations in the future in human vaccination. Moreover, the highly cross-reactive 60-kDa OMP seems to be an important antigenic marker of M. catarrhalis, and, as it is responsible for the induction of an antibody-mediated and long-lasting immune response, studying it may partially aid us in understanding the relatively low degree of pathogenicity of the bacterium in immunocompetent individuals.

The strongest resistance of Staphylococcus aureus to erythromycin is caused by decreasing uptake of the antibiotic into the cells

“…Further research on the most highly resistant strains is needed, especially experiments concerning cell wall composition and the genetic determinants responsible for such strong resistance. Successful selections and detections for membrane molecular targets are possible [23,24].…”

Virulence factors of Moraxella catarrhalis outer membrane vesicles are major targets for cross-reactive antibodies and have adapted during evolution

“…Many immune-relevant and shared microbial epitopes stimulate the production of intraspecies and interspecies cross-reacting antibodies with high frequency and have cross-protective efficiency 24 , 25 .…”

The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase against Moraxella catarrhalis

“…OMP CD is a highly conserved and abundantly expressed M. catarrhalis surface protein identified as a target of serum IgG antibodies to surface epitopes in the majority of adults with COPD who cleared this pathogen as well as mucosal IgA in COPD patients [ 40 , 41 ]. OMP CD is recognized intensively by cross-reactive intraspecies antibodies from mice sera and human sera in healthy children and those with otitis media [ 42 , 43 ]. Functionally, this protein is involved in complement resistance [ 32 ].…”