The effects of age, sex, and possible prior exposure to serogroup C meningococci on group C-specific antibody levels (total and functional) were examined in 2- to 19-year-olds just before and 1 and 12 months after immunization with divalent (groups A + C) meningococcal capsular polysaccharide vaccine. Only age was found to have a significant effect on antibody levels. At 1 month, only 50% of 2- to 6-year-olds had detectable serum bactericidal antibody, in contrast to 84.1% and 96.3% of 9- to 12- and 13- to 19-year-olds respectively. By 12 months, only 20%, 40.9%, and 53.8% of subjects in these age groups had serum bactericidal antibody, suggesting that current meningococcal C polysaccharide vaccines provide only short-term protection. However, the drop in total specific antibody levels (by EIA) was less pronounced. Persistence of antibodies detectable by EIA (but not serum bactericidal antibodies) suggests that this vaccine may also give rise to antibodies of low affinity or directed to nonfunctional (nonprotective) epitopes (or both).
We performed field trials in the course of an epidemic in Finland to learn whether Group A memingococcal capsular polysaccharide vaccine protects infants and young children from meningitis. The first trial involved 130,178 children between the ages of three months and five years; 49,295 children received the vaccine, 48,977 received a control Haemophilus influenzae Type b polysaccharide vaccine, and 31.906 remained unvaccinated. No cases of meningitis or sepsis caused by Group A meningococci were seen in the first year of observation among the children vaccinated with meningococcal vaccine whereas six occurred among those vaccinated with the H. influenzae vaccine and 13 among those not vaccinated. In the second trial 21,007 children of the same ages received the meningococcal vaccine. No cases caused by Group A occurred among those vaccinated, although five to seven would have been expected within the year. Meningococcal Group A vaccine appears efficacious in young infants and children.
Passive hemagglutination (HA), a bactericidal activity test (BCA), and radioimmunoassay (RIA) were compared in measuring serum antibodies before and after group A meningococcal capsular polysaccharide vaccination of servicemen. The three methods were found satisfactory in demonstrating a response to vaccination in this age group. Of the postimmunization sera, 5% remained without HA and 1% remained without BCA activity; 1% of the postimmunization sera had less than 2 micrograms of antibody per ml as measured by RIA. Approximately 60% of the serum pairs showed a greater than or equal to 32-fold rise in HA titer, a greater than or equal 25-fold rise in BCA titer, or a greater than or equal to 4-fold rise in antibody concentration by RIA. A difference in response to two different vaccine lots was seen with RIA and BCA. Although the calculated correlation between the three methods was good, some individual sera gave discrepant results. These could be shown to be due mainly to one of the following factors: low HA titer was due to lack of the immunoglobulin M and A classes of antibodies, low BCA titer was due to the blocking effect of high immunoglobulin A content, and high BCA titer was due to antibodies directed to bacterial components other than the capsular polysaccharide.
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The authors demonstrated a marked dissociation of the Neisseria meningitis cultures and the capacity to their rapid change from S- to R-forms. Differential signs of the S- and R-forms are described. Differences in the degree of dissociation of the cultures depending on their origin were shown: strains isolated from the cerebrospinal fluid and the blood of patients with meningitis proved to be less dissociated, and those isolated from carriers--more dissociated. Transfers from media to media and adaptation of cultures to artificial nutrient media produced the greatest influence on dissociation of the freshly isolated strains.
Sampling of sera from 202 Sudanese and 124 Swedish children 1-14 years of age was conducted at the end of the 1980s presenting an opportunity to compare the seroprevalence of anti-Neisseria meningitidis (MC) serogroup A antibodies in an area immediately before outbreak of an epidemic (Sudan 1988) with a low endemic area (Sweden). An ELISA antibody assay was developed for detection of antibodies against capsular polysaccharide of MC serogroup A and Haemophilus influenzae type b (Hib). Serum antibody against MC serogroup A was found significantly more frequently in Sudanese than in Swedish children. This indicates that factors other than herd immunity, as measured by serum antibodies against MC serogroup A polysaccharide, are important for avoidance of an MC serogroup A epidemic. The seroprevalence of Hib antibodies was, in contrast, significantly higher in Swedish than in Sudanese children, especially for 5-9-year-old children. A possible explanation may be the different systems of day-care of children in the two countries.
During an epidemic caused by group-A, sulphonamide-resistant meningococci in Finland, group-A polysaccharide vaccine was administered in 1974 to 16 458 recruits of the Armed Forces, leaving 20 748 as controls. Specific antibody response was good, and after vaccination only 1% of the men were without anti-meningococcal group-A antibodies. Pharyngeal carriage of the epidemic strain was low, about 1-5%, in the men when entering service. Group-A meningococcal disease occurred during the nine months' mean observation period in 1 of the vaccinated men (an annual incidence of 11 per 100 000) and in 8 of those not vaccinated (71 per 100 000), indicating 89% protective effect of the vaccine. Furthermore, the total number of cases of group-A meningococcal disease was reduced to non-epidemic levels at a time when 36% of the men in service were vaccinated, and has remained low for the next twelve months even though the epidemic in the general population continued.
For more than 15 years, Norway has had the highest incidence of meningococcal disease in northern Europe, with 80% of cases being due to serogroup B meningococci. The case-fatality has remained high, at about 10%. In this study, an outer membrane vaccine, which had previously been shown to induce an increase in bactericidal antibodies to the parent strain, was assessed in a large-scale, randomised, double-blind trial. From October, 1988, 171,800 students in secondary schools volunteered to take part in a double-blind, placebo-controlled, efficacy trial with school as the randomisation unit. Hospitals and clinics that routinely receive patients with infectious disease were asked to report urgently all cases of suspected meningitis and/or septicaemia in 13-21-year-old students in Norway. These cases were registered and further investigated according to a detailed protocol. 89 out of the 221 cases investigated by June 3, 1991, were shown to be severe systemic disease due to group B meningococci. 36 cases in 35 schools took part in the trial (11 schools with vaccinated students and 24 with students given placebo). The calculated rate of protection was thus 57.2% (p = 0.012, one-sided test). The findings suggest that, although the vaccine conferred protection against group B meningococcal disease, the effect was insufficient to justify a public vaccination programme.
Comment In: Lancet. 1991 Dec 7;338(8780):1456-71683438
BACKGROUND AND METHODS. Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS. Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS. The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.
We have developed an enzyme-linked immunosorbent assay (ELISA) in order to quantitate antimeningococcal IgM and IgG serum antibodies. The B:15 meningococcal strain was used as coating antigen, and class specific antibodies were detected by using alkaline phosphatase labelled rabbit anti-human IgM or IgG as conjugate. The specific IgG activity was higher in sera from healthy meningococcal carriers than non-carriers, but the difference was not statistically significant. Antimeningococcal IgM serum antibodies were more frequent in carriers that in non-carriers. Acute sera from 34 patients with fulminant meningococcal disease contained less specific IgG and had a higher prevalence of IgM than healthy carriers and non-carriers. By combining measurement of antimeningococcal IgG and IgM antibodies in both acute and convalescent sera 15/18 meningococcal patients demonstrated an increase in either IgG and IgM antibodies during the hospital stay, giving a sensitivity of 83%. 8/118 individuals without meningococcal disease had detectable specific IgM antibodies in their serum, giving a clinical specificity of the test of 93%. We conclude that quantitation of specific IgG antimeningococcal antibodies by a whole bacteria ELISA test may be a useful test for the study of immunity against meningococcal disease in single individuals as well as in epidemiological studies. The combined use of the IgG and IgM tests is helpful in the diagnosis of meningococcal disease when blood or cerebrospinal fluid cultures are negative.