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Thirteen Neisseria meningitidis serogroups have been described on the basis of serologic differences of the capsule; of these 13 serogroups, 6 (A, B, C, W, X, Y) cause invasive meningococcal [...]

In the present study we examine the potential use of oligonucleotide probes to characterize Neisseria meningitidis serotypes without the use of monoclonal antibodies (MAbs). Antigenic diversity on PorB protein forms the bases of serotyping method. However, the current panel of MAbs underestimated, by at least 50% the PorB variability, presumably because reagents for several PorB variable regions (VRs) are lacking, or because a number of VR variants are not recognized by serotype-defining MAbs12. We analyzed the use of oligonucleotide probes to characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene sequence for the prototype strain of serotype 10 was determined, aligned with 7 other porB sequences from different serotypes, and analysis of individual VRs were performed. The results of DNA probes 21U (VR1-A) and 615U (VR3-B) used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for characterizing serotypes possible can type 100% of the PorB VR diversity. It is a simple and rapid method specially useful for analysis of large number of samples.

Withdrawal of the terminal lipid from the polysaccharide (PS) by treatment with phospholipase A2 or phospholipase D disrupts the association of a part of the PS with vesicles which result from incubation of native PS from group C Neisseria meningitidis or Haemophilus influenzae type b with isolated outer membrane vesicles. Delipidated PSs are not appropriate as solid-phase antigens in enzyme-linked immunosorbent assay.

The primary structure of the lipid A component of the lipopolysaccharide of Neisseria meningitidis was elucidated. Analyses showed that meningococcal lipid A consists of a beta-D-glucosaminyl-(1'-6)-D-glucosamine disaccharide backbone with ester- and amide-linked 3-hydroxy fatty acids. It also contains amide-bound (R)-3-acyloxyacyl groups. The phosphate groups are substituted nonstoichiometrically by O-phosphorylethanolamine. The meningococcal lipid A differs from Escherichia coli-type lipid A in the location and chain lengths of acyl groups, and exhibits a highly symmetrical structure with regard to the distribution of both fatty acids and polar phosphate groups.

Haemophilus influenzae is an organism that causes a variety of illnesses of which meningitis is the most serious. Infection is most common in young children under one year. Older children and adults are protected against H. influenzae infection by the development of antibodies against the organism. Two vaccines have been developed to protect children against H. influenzae infection by stimulating production of antibodies against this organism. (The PRP vaccine contains polysaccharides, or sugar chains, from the organism, and the PRP-D vaccine contains polysaccharides conjugated to an immune response-stimulating protein.) The effectiveness of the vaccines in the US has been lower than expected. The occurrence of H. influenzae disease after vaccination with polysaccharide (PRP) or conjugate (PRP-D) vaccine was evaluated using reports from 4.5 million administered doses of PRP and 2.0 million doses of PRP-D. Haemophilus b disease was reported in 150 children who received PRP vaccine, while 26 cases of disease were reported after PRP-D vaccination. The rate of PRP-D-associated disease was 30 percent of that observed with PRP vaccine. The rate of early-onset disease, or illness occurring within 15 days after vaccination, was similar for both vaccines. Meningitis was involved in 60 percent of PRP-D cases and 54 percent of PRP cases. Epiglottitis (swelling of the airway) occurred in 6 percent of PRP-D cases, compared with 25 percent of PRP cases. These findings suggest that PRP-D vaccine is more effective than PRP vaccine. (Consumer Summary produced by Reliance Medical Information, Inc.)

Postmarketing surveillance of vaccines may be needed to insure that they retain their effectiveness. The case of Merck's conjugated Haemophilus influenza type b (Hib) vaccine, known as PedvaxHib, is discussed. Conjugated vaccines are complex vaccines. In the case of the Hib vaccine a bacterial polysaccharide is linked to a protein carrier. Researchers studying the effectiveness of various dosing schedules for Hib vaccines in infants found that one lot of Merck's vaccine produced lower immune system responses in infants than were expected. This occurred despite the fact that each lot of Merck's vaccine was subject to tests by the Center for Biologics Evaluation and Research of the Food and Drug Administration before being released for sale. Merck then reviewed the vaccine-manufacturing process and four additional tests were added to the prerelease requirements. Other Hib vaccines have also been reported to produce lower than expected immune system responses in infants. In addition to postmarketing surveillance, further research is needed to develop accurate tests of effectiveness for other conjugate vaccines under development.