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

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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.

Abbreviations

AFM:

atomic force microscopy

BSA:

bovine serum albumin

EDTA:

ethylenediaminetetracetic acid

ELISA:

enzyme-linked immunosorbent assay

HRP:

horseradish peroxidase

LOS:

lipooligosaccharide

OMPs:

outer membrane proteins

OMPs-PC and PC-OMPs:

the studied proteoliposomes

OMPs-Z:

Zwittergent-based micelles of OMPs

OPD:

o-phenylenediamine

PBS:

phosphate buffered saline

PC:

phosphatidylcholine

TPBS:

PBS supplemented with Tween 20

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Correspondence to Daria Augustyniak.

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Key words

  • Moraxella catarrhalis
  • Outer membrane proteins
  • Proteoliposomes
  • Proteomicelles
  • Anti-OMP antibodies
  • Cross-reactivity
  • Zwittergent