transferrin-binding proteins, chemically modified group B polysaccharide conjugated to a carrier protein, meningococcal lipopolysaccharides, and the outer membrane proteins (OMPs).

Several vaccines based on OMPs have been assessed in clinical trials. Results from the most recent of these studies indicate the vaccines can be as much as 80 percent efficacious in those over 4 years of age. In younger individuals, however, efficacy drops significantly. And in those initially protected, antibody responses are not long lasting, even when a booster dose of vaccine is administered. At least in one study,15 the bulk of the antibodies produced by immunization did not have bactericidal activity, suggesting the antibody response may be directed against the wrong OMP epitopes.

Some of these shortcomings might be overcome (Box 2). For example, one step might be to eliminate the class 4 OMP in order to avoid the induction of “blocking” antibody—antibody that may interfere with an otherwise protective immune response. However, recent work by investigators at the Walter Reed Army Institute of Research revealed very little difference in bactericidal titers between vaccines containing class 4 OMP and those without these proteins. More effective adjuvants, such as QS-21 (a plant-derived glucoside) and MPL (monophosphoryl lipid A), and increasing the number of doses to three, might also improve vaccine efficacy. In a Chilean study of a group B vaccine, 16 antibody response among vaccinees continued to increase even after the last dose, suggesting that subsequent natural infection, or carriage, served to enhance the immune response. Researchers may want to evaluate mucosal (intranasal) immunization with native antigens in order to mimic the booster effect seen with natural carriage.

One important unresolved question in the design of group B vaccines is whether or not protection is serotype specific.17 An additional concern is that OMP is a complex antigen, containing many proteins, lipopolysaccharides, and even some capsular polysaccharide —all of which may stimulate the production of antibodies. Researchers currently have no way of knowing which antibodies, or combinations of antibodies, are responsible for immunologic protection.18

Scientists for years have set their hopes on a meningococcal vaccine that would provide protection against all three primary serogroups. Given the difficulty in developing an effective group B product and the progress that is being made toward an effective A/C conjugate, however, a wiser strategy might

15  

Zollinger, WD, Boslego, J, Moran, E, Gracia, J, Cruz, C, Brandt, B, et al., The Chilean National Committee for Meningococcal Disease: Meningococcal serogroup B vaccine protection trial and follow-up studies in Chile. NIPH Annals 14:211, 1991.

16  

See footnote 15.

17  

Claire Broome.

18  

Helena Makela.



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