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Outer membrane proteins of Neisseria meningitidis: structure and importance in meningococcal disease
Abstract:
Meningococcal meningitis is a serious disease with a high incidence in children. Since meningococcal surface structures play a role in invasion of the host and initiation of disease, host defense mechanisms are directed against these meningococcal structures. All virulent meningococci are encapsulated, but other factors are also involved. Only certain serotypes of group B and group C meningococci are strongly associated with disease. Our studies have been directed toward a better understanding of the structure of the meningococcal cell surface. There are five classes of major outer membrane proteins exposed on the cell surface, designated class 1 through 5, based in part upon the protein's molecular weight. Using monoclonal antibodies we have shown that antibodies to the class 1, 2 and 5 proteins of serotype 2 are bactericidal and therefore probably protective. Convalescent sera of meningococcal disease patients have elevated antibody levels to each of these classes of proteins. Outer membrane protein vaccines have been prepared, and clinically evaluated in adults and children as young as 6 mo of age. The vaccines induce serotype specific bactericidal antibodies in all age groups, but they induced lower levels in young children. We are now working to improve the immune response of children through the use of aluminium adjuvants.
Insights
Meningococcal meningitis vaccines target outer membrane proteins. While effective in adults, lower antibody levels in children necessitate adjuvant research for improved immune response against this serious childhood disease.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Meningococcal meningitis is a significant childhood illness.
- Host defenses target meningococcal surface structures, crucial for invasion and disease initiation.
- Virulent meningococci possess capsules, and other factors, with specific serotypes (B and C) strongly linked to disease.
Purpose of the Study:
- To understand the structure of the meningococcal cell surface.
- To identify potential vaccine targets on the meningococcal outer membrane.
- To evaluate the efficacy of outer membrane protein vaccines in different age groups.
Main Methods:
- Characterization of meningococcal outer membrane proteins (classes 1-5).
- Utilizing monoclonal antibodies to assess antibody function (bactericidal activity).
- Clinical evaluation of outer membrane protein vaccines in adults and children.
Main Results:
- Antibodies to class 1, 2, and 5 outer membrane proteins of serotype 2 were found to be bactericidal and likely protective.
- Convalescent sera from patients showed elevated antibody levels against these protein classes.
- Outer membrane protein vaccines induced serotype-specific bactericidal antibodies across age groups, albeit at lower levels in young children.
Conclusions:
- Meningococcal outer membrane proteins are viable targets for vaccine development.
- Current vaccines show promise but require optimization for robust immune responses in infants and young children.
- Adjuvant strategies, such as aluminum adjuvants, are being investigated to enhance vaccine immunogenicity in pediatric populations.