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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Evaluation of a 74-kDa transferrin-binding protein from Moraxella (Branhamella) catarrhalis as a vaccine candidate
D Chen1, J C McMichael, K R VanDerMeid
1Wyeth-Lederle Vaccines, New York, NY 14586-9728, USA.
Abstract:
An outer membrane protein from Moraxella catarrhalis with a mass of 74-kDa was isolated and evaluated as a vaccine candidate. The 74-kDa protein binds transferrin, and appears to be related to the other proteins from the organism that are reported to bind transferrin. The 74-kDa protein possessed conserved epitopes exposed on the bacterial surface. This is based on the reactivity with whole bacterial cells as well as complement dependent bactericidal activity of sera from mice immunized with the isolated proteins from the O35E and TTA24 isolates. However, there was divergence in the degree of antibody cross-reactivity with the protein from one strain to another. This serotypic divergence was reflected in both the complement-dependent bactericidal activities of the antibodies elicited in mice and the capacity of immune mice to clear the bacteria in a murine pulmonary model. Antibodies affinity purified from human plasma lacked bactericidal activity even though they were reactive with all the tested isolates. The 74-kDa protein appears to be a good vaccine candidate, but more studies are needed to understand its antigenic variability and whether antibodies toward it are protective.
Insights
A 74-kDa outer membrane protein from Moraxella catarrhalis shows promise as a vaccine candidate due to conserved surface epitopes. However, variability in antibody responses and protective efficacy requires further investigation.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Moraxella catarrhalis is a significant respiratory pathogen.
- Outer membrane proteins are key targets for vaccine development against bacterial infections.
Purpose of the Study:
- To evaluate a 74-kDa outer membrane protein of Moraxella catarrhalis as a potential vaccine candidate.
- To assess the immunogenicity and protective efficacy of the 74-kDa protein in preclinical models.
Main Methods:
- Isolation and characterization of a 74-kDa outer membrane protein.
- Immunization of mice with the isolated protein.
- Assessment of antibody responses, including complement-dependent bactericidal activity.
- Evaluation of bacterial clearance in a murine pulmonary infection model.
Main Results:
- The 74-kDa protein binds transferrin and has conserved, surface-exposed epitopes.
- Immunization elicited complement-dependent bactericidal antibodies in mice, but with strain-specific cross-reactivity.
- Serotypic divergence impacted antibody efficacy and bacterial clearance in a murine model.
- Human antibodies reactive with the protein lacked bactericidal activity.
Conclusions:
- The 74-kDa outer membrane protein is a potential vaccine candidate for Moraxella catarrhalis.
- Antigenic variability and the protective capacity of elicited antibodies need further study.
- Understanding immune responses is crucial for developing effective vaccines against this pathogen.
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