Immune response capacity after human splenic autotransplantation: restoration of response to individual pneumococcal vaccine subtypes.
OBJECTIVE: To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. SUMMARY BACKGROUND DATA: After splenectomy, patients have an increased risk of overwhelming infection or sepsis involving encapsulated bacteria such as pneumococci. The value of human spleen autotransplantation after splenectomy because of trauma has long been questioned. Mononuclear phagocyte system function appeared to be similar to that in splenectomized persons. The presence of specific antipneumococcal antibodies would allow other parts of the mononuclear phagocyte system, such as those in the liver, to phagocytose opsonized bacteria. METHODS: Ten consecutive patients undergoing splenectomy followed by autotransplantation were compared with the next 14 consecutive patients undergoing splenectomy alone. After a minimum of 6 months, the patients were vaccinated with 23-valent pneumococcal vaccine. Blood samples were taken at the time of vaccination and after 3 and 6 weeks for antipneumococcal capsular polysaccharides IgM and IgG enzyme-linked immunosorbent assay against types 3, 4, 6, 9, 14, and 23. Splenic regrowth was evaluated by scintigraphy. RESULTS: Surprisingly, several of the nonautotransplanted patients showed scintigraphic activity, indicating the presence of either accessory spleens or traumatic seeding (splenosis). Significant antibody titer increases (more than twofold) were found for both IgM and IgG in the autotransplanted patients. Splenectomized-only patients showed no significant increase in Ig levels in patients without splenic regrowth and partial improvement in patients with splenosis/accessory spleens. CONCLUSIONS: Considering this significant antipneumococcal antibody increase, spleen autotransplants can be expected to permit an adequate humoral response to pneumococcal infections and presumably also to other TI-2 antigens, and to protect against overwhelming postsplenectomy infection or sepsis. (+info)
Epidemiology of Streptococcus pneumoniae infection in Malaysia.
During a 1-year period from October 1995 to September 1996, 273 isolations of Streptococcus pneumoniae were made from various types of clinical specimens. The majority of the isolates (39.2%) were from sputum whilst 27.5% were from blood, CSF and other body fluids. The organism was isolated from patients of all age groups, 31.1% from children aged 10 years and below, 64.7% of which come from children aged 2 years or below. The majority of the isolates belong to serotypes 1, 6B, 19B, 19F and 23F. Serotypes 1 and 19B were the most common serotypes associated with invasive infection. About 71.9% of the invasive infections were due to serotypes included in the available 23 valent polysaccharide vaccine. The rates of resistance to penicillin and erythromycin were 7.0 and 1.1% respectively. Our findings show that the serotypes of S. pneumoniae causing most invasive infections in Malaysia are similar to those in other parts of the world and the available vaccine may have a useful role in this population. (+info)
Pneumococcal conjugate vaccine primes for polysaccharide-inducible IgG2 antibody response in children with recurrent otitis media acuta.
Children with frequent recurrent episodes of otitis media may have a deficient IgG2 antibody response to polysaccharide antigens. Five otitis-prone children were vaccinated with heptavalent pneumococcal conjugate vaccine. While all had an IgG1 antibody response to all pneumococcal serotypes included in the conjugate vaccine, the IgG2 response, especially to serotypes 6B, 9V, 19F, and 23F, was poor. However, vaccination with a 23-valent polysaccharide vaccine 6 months after conjugate vaccination induced an 11.5- to 163-fold increase in IgG2 anti-polysaccharide antibody titers. Thus, an IgG2 polysaccharide antibody deficiency can be overcome by priming with a pneumococcal conjugate vaccine followed by a booster with a polyvalent polysaccharide vaccine. (+info)
Levels of proinflammatory cytokines in plasma after pneumoccoccal immunization in human immunodeficiency virus type 1-infected patients.
To ascertain if immunization with pneumococcal polysaccharide vaccine is associated with rises in the levels of proinflammatory cytokines in the plasma of human immunodeficiency virus type 1 (HIV-1)-infected patients, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured serially after immunization. IL-6 levels rose an average of 2.2- and 2.1-fold 6 and 8 h after immunization, respectively, but TNF-alpha levels remained unchanged. The levels of these cytokines were stable in unimmunized controls. Immunization with pneumococcal polysaccharide vaccine induces increases in the levels of IL-6 in the plasma of persons with HIV-1 infection. (+info)
Avidity as a determinant of the protective efficacy of human antibodies to pneumococcal capsular polysaccharides.
Antibodies reactive with capsular polysaccharides are considered the principal mediators of immunity against invasive diseases caused by Streptococcus pneumoniae. In this study, we tested the hypothesis that anti-pneumococcal capsular polysaccharide (PPS) antibody avidity can influence protective efficacy. We measured the avidities of individual adult postvaccination immunoglobulin G2 (IgG2) antibodies to PPS serotypes 6B and 23F and examined the relationship between avidity and opsonophagocytic and mouse-protective activities. The avidities of PPS 6B- and PPS 23F-specific IgG2 antibodies ranged from 6 to 31 nM-1 and from 3 to 20 nM-1, respectively. We observed an inverse correlation between the magnitude of avidity and the amount of antibody required to protect mice against lethal bacteremia caused by serotype 6B pneumococci. Similarly, higher-avidity antibodies were more effective than lower-avidity antibodies in vitro in mediating complement-dependent opsonophagocytosis of both 6B and 23F pneumococci. These data suggest that in adults, PPS antibodies are sufficiently polymorphic to possess biologically significant variations in avidity. We conclude that avidity functions as an important determinant of anticapsular antibody protective efficacy against pneumococci. (+info)
Improving pneumococcal vaccine rates. Nurse protocols versus clinical reminders.
OBJECTIVE: To compare the effectiveness of three interventions designed to improve the pneumococcal vaccination rate. DESIGN: A prospective controlled trial. SETTING: Department of Veterans Affairs ambulatory care clinic. PATIENTS/PARTICIPANTS: There were 3, 502 outpatients with scheduled visits divided into three clinic teams (A, B, or C). INTERVENTIONS: During a 12-week period, each clinic team received one intervention: (A) nurse standing orders with comparative feedback as well as patient and clinician reminders; (B) nurse standing orders with compliance reminders as well as patient and clinician reminders; and (C) patient and clinician reminders alone. Team A nurses (comparative feedback group) received information on their vaccine rates relative to those of team B nurses. Team B nurses (compliance reminders group) received reminders to vaccinate but no information on vaccine rates. MEASUREMENTS AND MAIN RESULTS: Team A nurses assessed more patients than team B nurses (39% vs 34%, p =.009). However, vaccination rates per total patient population were similar (22% vs 25%, p =.09). The vaccination rates for both team A and team B were significantly higher than the 5% vaccination rate for team C (p <.001). CONCLUSIONS: Nurse-initiated vaccine protocols raised vaccination rates substantially more than a physician and patient reminder system. The nurse-initiated protocol with comparative feedback modestly improved the assessment rate compared with the protocol with compliance reminders, but overall vaccination rates were similar. (+info)
Pneumococcal capsular polysaccharide preparations may contain non-C-polysaccharide contaminants that are immunogenic.
We measured the capacity to opsonize Streptococcus pneumoniae serotype 6B and estimated the concentration of immunoglobulin G anti-6B capsular polysaccharide (PS) antibodies in 25 pre- and postimmune sera from adults immunized with a pneumococcal PS vaccine. We first studied two postvaccination serum samples displaying less opsonophagocytic capacity than expected. The majority of anti-6B antibodies in the two samples reacted with the capsular PSs of several unrelated serotypes (2, 4, 9V, 19F, and 23F) and with the lysate of noncapsulated S. pneumoniae bacteria but not with C-PS. The non-type-specific antibodies accounted for at least one-half of anti-6B antibodies in 40% of prevaccination sera and 10% of postvaccination sera from adults. The non-type-specific antibodies could be demonstrated in the enzyme-linked immunosorbent assays (ELISAs) for pneumococcal antibodies to other serotypes (4, 9V, 18C, 19F, and 23F). The nonspecific antibodies appear to bind a contaminant(s) in the current preparations of capsular PS. ELISA for antibodies to pneumococcal capsules may not be serotype specific for some samples. (+info)
A flow cytometric opsonophagocytic assay for measurement of functional antibodies elicited after vaccination with the 23-valent pneumococcal polysaccharide vaccine.
Opsonophagocytosis is the primary mechanism for clearance of pneumococci from the host, and the measurement of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. We developed a semiautomated flow cytometric opsonophagocytosis assay using HL-60 granulocytes as effector cells and nonviable 5, 6-carboxyfluorescein, succinimidyl ester-labeled Streptococcus pneumoniae (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) as bacterial targets. The flow cytometric opsonophagocytosis assay was highly reproducible (for 87% of repetitive assays the titers were within 1 dilution of the median titer) and serotype specific, with >/=97% inhibition of opsonophagocytic titer by addition of homologous serotype-specific polysaccharide. In general, opsonophagocytic titers were not significantly inhibited by the presence of either heterologous pneumococcal polysaccharide or penicillin in the serum. The flow cytometric assay could reproducibly measure functional antibody activity in prevaccination (n = 28) and postvaccination (n = 36) serum specimens from healthy adult volunteers vaccinated with the 23-valent pneumococcal polysaccharide vaccine. When compared with a standardized manual viable opsonophagocytic assay, a high correlation (r = 0.89; P +info)