Surveillance of invasive Streptococcus pneumoniae infection in the province of Quebec, Canada, from 1996 to 1998: serotype distribution, Antimicrobial susceptibility, and clinical characteristics.
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In the province of Quebec, Canada, from 1996 to 1998, 3,650 invasive Streptococcus pneumoniae infections were reported. A total of 1,354 isolates were serotyped and tested for antimicrobial susceptibility. The distribution of serotypes remained stable over the 3 years, with serotypes 14, 6B, 4, 9V, 23F, and 19F accounting for 61% of the isolates. Overall, 90% of isolates were included in the current 23-valent vaccine and 67% were included in the 7-valent conjugate vaccine. We were able to determine that resistance to penicillin and to other antibiotics is increasing. (+info)
Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice.
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The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively. (+info)
Efficacy of a pneumococcal conjugate vaccine against acute otitis media.
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BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine. (+info)
Safety and immunogenicity of improved Shigella O-specific polysaccharide-protein conjugate vaccines in adults in Israel.
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Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678-3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPAsucc for evaluation in children. (+info)
Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection.
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The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of > or =4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of > or =8 showed that for 93% (27 of 29) the titer was > or =4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or > or =128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of > or =128 had hSBA titers of > or =4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of > or =4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result > or =4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of > or =128 after a 10-microg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-microg dose. Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory. (+info)
Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib).
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Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 microg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0.15 microg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice. (+info)
Randomized trial of the immunogenicity of fractional dose regimens of PRP-T Haemophilus influenzae type b conjugate vaccine.
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To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively. (+info)
Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine protects animals from experimental sepsis.
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The passive infusion of antibodies elicited in rabbits with a detoxified J5 lipopolysaccharide (LPS)/group B meningococcal outer membrane protein complex vaccine protected neutropenic rats from heterologous lethal gram-negative bacterial infection. In this study, active immunization was studied in neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a > 200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the duration of cyclophosphamide-induced neutropenia and for < or = 3 months. There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazidime-treated rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < 0.01 for each comparison). Immunized animals had lower levels of bacteria in organs and lower levels of circulating endotoxin at the onset of fever. In conclusion, active immunization with an anti-endotoxin vaccine improved survival after infection with > or = 2 heterologous, clinically relevant bacterial species in immunocompromised animals. Active immunization with this vaccine merits further investigation. (+info)