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ABSTRACT: BACKGROUND:: We have previously shown that the 7-valent pneumococcal conjugate vaccine (PncCRM) given in infancy is effective in reducing tympanostomy tube placements up to 4 to 5 years of age. This study aimed to assess the effectiveness of pneumococcal conjugate vaccines PncCRM and PncOMPC from 2 up to 13 years of age. METHODS:: Altogether 2497 children participated in the Finnish Otitis Media Vaccine trial conducted in 1995-99 and were vaccinated at 2, 4, 6 and 12 months of age with PncCRM or PncOMPC or hepatitis B vaccine as controls. The data for tympanostomy tube placements were collected from health registers including hospital and private office operations. Vaccine efficacy was estimated by comparing incidences of tympanostomies from 2 to 12-13 years of age in each of the pneumococcal vaccine groups with the control group. RESULTS:: Register data were searched for 2474 subjects. A total of 535 tympanostomy tube placements were identified in the health registers from 1998 through 2008 with a cumulative incidence of 14.6% from 2 to 13 years of age in the control group. The vaccine impact was age-dependent: from 2 through 5 years of age the vaccine effectiveness was 34% (95% confidence interval 1 to 52%) for PncCRM and 6% (-28 to 31) for the PncOMPC vaccine. For the age group of 6 to 12-13 years the vaccine effectiveness estimates for the PncCRM and PncOMPC groups were -13% (-137 to 46) and -2% (-123 to 54), respectively. CONCLUSIONS:: PncCRM vaccine reduced the tympanostomy tube placements up to 5 years of age. No impact on new surgical procedures could be demonstrated after that but the benefit achieved was sustained.
The Pediatric Infectious Disease Journal 11/2012; · 3.58 Impact Factor
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ABSTRACT: Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.
Clinical and vaccine immunology: CVI 11/2011; 19(1):96-9. · 2.37 Impact Factor
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ABSTRACT: We assessed the development and role of serum anti-CbpA and -PhtD in early childhood in relation to pneumococcal exposure. Serum IgG concentrations to CbpA and PhtD were measured with enzyme immunoassay in serum samples collected at the ages of 6, 12, 18, and 24 months from 50 healthy children and from 50 adults. Furthermore, antibodies to CbpA, PhtD and the C-terminal fragment of PhtD (PhtD C) were measured in serum samples collected at 12 (N=286) and 18 months (N=259) to evaluate the risk of subsequent pneumococcal acute otitis media (AOM) in relation to antibody concentrations. The increase in anti-CbpA and -PhtD concentrations was related to prior pneumococcal exposure. At 12 and 18 months, in the risk model of pneumococcal AOM adjusted for prior pneumococcal AOM, higher concentrations of anti-CbpA, but not anti-PhtD, were associated with a lowered risk of subsequent pneumococcal AOM. In conclusion, pneumococcal exposure induces the development of serum anti-CbpA and -PhtD in early childhood. Anti-CbpA antibodies may play a role in the prevention of subsequent pneumococcal AOM during the second year of life.
Vaccine 07/2009; 27(34):4615-21. · 3.77 Impact Factor
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ABSTRACT: PspA is a structurally variable surface protein important to the virulence of pneumococci. PspAs are serologically cross-reactive and exist as two major families. In this study, we determined the distribution of PspA families 1 and 2 among pneumococcal strains isolated from the middle ear fluid (MEF) of children with acute otitis media and from nasopharyngeal specimens of children with pneumococcal carriage. We characterized the association between the two PspA families, capsular serotypes, and multilocus sequence types (STs) of the pneumococcal isolates. MEF isolates (n = 201) of 109 patients and nasopharyngeal isolates (n = 173) of 49 children were PspA family typed by whole-cell enzyme immunoassay (EIA). Genetic typing (PCR) of PspA family was done for 60 isolates to confirm EIA typing results. The prevalences of PspA families 1 and 2 were similar among pneumococci isolated from MEF (51% and 45%, respectively) and nasopharyngeal specimens (48% each). Isolates of certain capsule types as well as isolates of certain STs showed statistical associations with either family 1 or family 2 PspA. Pneumococci from seven children with multiple pneumococcal isolates appeared to express serologically different PspA families in different isolates of the same serotype; in three of the children the STs of the isolates were the same, suggesting that antigenic changes in the PspA expressed may have taken place. The majority of the isolates (97%) belonged to either PspA family 1 or family 2, suggesting that a combination including the two main PspA families would make a good vaccine candidate.
Clinical and vaccine immunology: CVI 09/2008; 15(10):1555-63. · 2.37 Impact Factor
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ABSTRACT: Elderly individuals are susceptible to pneumococcal infections. Although factors contributing to the increased susceptibility of the elderly to bacterial infections may be several, compromised immune function, a consequence of normal human ageing, is widely accepted to play a role. We evaluated the effect of ageing on the concentrations of naturally acquired antibodies to pneumococcal capsular polysaccharides (PPS) and protein antigens. The concentrations of immunoglobulin G (IgG) and IgM antibodies to the PPS of serotypes 3, 4, 6B, 9V, 14, and 23F and IgG antibodies to the pneumococcal virulence-associated proteins CbpA, LytC, PhtD and its C-terminal fragment (PhtD C), NanA, PspA fam1, and PspA fam2 were measured by enzyme immunoassay in the sera of younger (30 to 64 years of age) and elderly (65 to 97 years of age) adults. The concentrations of anti-PPS IgG against serotypes 3 and 6B, of anti-PPS IgM against serotypes 3, 4, 6B, 9V, and 23F, and of anti-protein IgG against all tested antigens were significantly lower in the elderly than in younger adults. A stronger decline in anti-PPS antibody concentrations was seen with age in women compared to men, while anti-protein antibody concentrations were mainly similar between the genders. Age, gender, and the nature of the antigen have substantial and varying effects on the antibody concentrations in the sera of adults.
Clinical and vaccine immunology: CVI 08/2008; 15(9):1391-7. · 2.37 Impact Factor
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ABSTRACT: Pneumococcal surface protein A (PspA) is a highly variable yet cross-reactive protein that exists as 2 major families. We assessed the development of human serum and salivary antibodies against the PspA families 1 (PspA1) and 2 (PspA2) in early childhood and their role in the prevention of pneumococcal acute otitis media (AOM).
Serum levels of IgG and salivary levels of IgA antibodies to PspA1 and PspA2 were measured by use of enzyme immunoassay from the samples from the Finnish Otitis Media Cohort Study obtained at the ages of 12 months (287 and 160 samples, respectively) and 18 months (258 and 131 samples, respectively). The Cox proportional hazard model was used to evaluate the relative risk (RR) of pneumococcal AOM during the 6 months after sampling relative to concentration of serum or presence of salivary anti-PspA in the samples.
Anti-PspA1 and anti-PspA2 concentrations at 12 and 18 months were related to prior culture-confirmed pneumococcal exposure. The concentrations of serum anti-PspA were not significantly associated with the risk of pneumococcal AOM. At 18 months, the presence of salivary anti-PspA was significantly associated with a lower risk of pneumococcal AOM during the 6 months after sampling (RR, 0.27 [95% confidence interval, 0.11-0.69]).
The lowered risk of pneumococcal AOM associated with the presence of salivary anti-PspA at 18 months suggests that mucosal anti-PspA antibodies have a role in the prevention of pneumococcal AOM.
The Journal of Infectious Diseases 12/2007; 196(10):1528-36. · 6.41 Impact Factor
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ABSTRACT: We examined naturally acquired antibodies to pneumococcal vaccine candidate proteins PhtB and PhtE in children during their first 2 years of life. Prior culture-confirmed pneumococcal exposure was shown to induce the development of anti-PhtB and -PhtE antibodies. The anti-PhtB or -PhtE antibody concentrations were not significantly associated with a decreased risk of subsequent pneumococcal acute otitis media.
The Pediatric Infectious Disease Journal 06/2007; 26(5):447-9. · 3.58 Impact Factor
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ABSTRACT: Pneumococcal neuraminidase, NanA, is a pneumococcal vaccine candidate. Prior culture-confirmed pneumococcal contacts were shown to induce serum anti-NanA antibodies during the first 2 years of life. The antibody concentrations at neither 12 nor 18 months were significantly associated with the risk of subsequent pneumococcal carriage or acute otitis media.
Clinical and Vaccine Immunology 11/2006; 13(10):1177-9. · 2.55 Impact Factor
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ABSTRACT: The putative pneumococcal proteinase maturation protein A is a potential pneumococcal vaccine candidate. We examined serum antipneumococcal proteinase maturation protein A antibodies at 6, 12, 18 and 24 months of age, and showed that the age-related development of antipneumococcal proteinase maturation protein A antibodies is associated with pneumococcal contacts. A higher antipneumococcal proteinase maturation protein A antibody concentration at 18 months of age tends to predict for a lower risk of pneumococcal acute otitis media in the following 6 months (relative risk: 0.84, 95% confidence interval: 0.62-1.13).
FEMS Immunology & Medical Microbiology 04/2006; 46(2):166-8. · 2.44 Impact Factor
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ABSTRACT: Respiratory viral infections are usually preceding or coinciding with acute otitis media (AOM) in children. It is not known if a given viral infection would facilitate invasion of bacterial pathogens into the middle ear in a species-specific way. We reanalysed the microbiological results of the two prospective Finnish Otitis Media (FinOM) studies for this purpose.
The children had been followed from 2 months to 2 years of age in specific study clinics and all referred AOM events were analysed. Combined results of virus detection tests from middle ear fluid and nasopharyngeal aspirate and those of bacterial culture from middle ear fluid were cross-tabulated for 529 AOM events in the FinOM Cohort Study and for 364 events in the FinOM Vaccine Trial.
In both studies the main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis while the main viruses detected were rhinoviruses and respiratory syncytial virus (plus enteroviruses in the Vaccine Trial). No distinct species-specific associations were observed between the viral and bacterial findings.
We did not find support to the theory that respiratory infection caused by a given viral species would favour growth of a certain bacterial pathogen in the MEF more than another.
The Journal of infection 04/2006; 52(3):181-7. · 4.13 Impact Factor
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ABSTRACT: Mucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response.
Healthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the age of 2, 4, and 6 months. At 12 months of age, 49 of them received the PncOMPC and 7 were vaccinated with the pneumococcal polysaccharide vaccine (PncPS) as a booster. The control group of 55 children received a hepatitis B vaccine at the same ages. Salivary anti-Pnc IgG, IgA, IgA1, and IgA2 antibodies to serotypes 6B, 14, 19F, and 23F were measured in both groups at the age of 7 and 13 months.
Salivary anti-Pnc IgG and IgA were detected more often in the PncOMPC than in the control group. However, the difference between groups was significant only for 19F and 23F IgA concentrations at the age of 7 months. At the age of 13 months, antibody concentrations did not differ between PncOMPC and control groups. The rises in IgA concentrations between 7 and 13 months of age were mainly of subclass IgA1. Further, there is a clear trend that PncPS booster induces higher salivary anti-Pnc PS antibody concentrations than the PncOMPC.
We found that PncOMPC can induce a mucosal IgA response. However, the actual impact of mucosal antibodies in protection against pneumococcal infections is not clear.
BMC Infectious Diseases 02/2005; 5:41. · 3.12 Impact Factor
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ABSTRACT: We studied salivary antibodies induced by a seven-valent pneumococcal conjugate vaccine (PncCRM). Healthy Finnish children (n=115), a subcohort of the Finnish Otitis Media (FinOM) Vaccine Trial, were immunised either with the PncCRM or a control vaccine (hepatitis B) at the age of 2, 4, 6, and 12 months. Salivary IgG, IgA, IgA1, IgA2 and sIg for serotypes 6B, 14, 19F, and 23F were measured at 7 and 13 months of age, and IgG and IgA also at 4-5 years of age. The PncCRM could induce both salivary anti-Pnc polysaccharide IgG and IgA. However, by the age of 4-5 years IgA concentrations had increased in both groups and were similar. The increases in IgA concentrations were mostly of IgA1 subclass. The difference between the PncCRM and the control group was more notable for serotypes 6B, 14 and 23F than for serotype 19F. We could not find evidence for the development of mucosal immunologic memory after vaccination with the PncCRM.
Vaccine 01/2005; 23(3):298-304. · 3.77 Impact Factor
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ABSTRACT: Abstract
Background
Mucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response.
Methods
Healthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the age of 2, 4, and 6 months. At 12 months of age, 49 of them received the PncOMPC and 7 were vaccinated with the pneumococcal polysaccharide vaccine (PncPS) as a booster. The control group of 55 children received a hepatitis B vaccine at the same ages. Salivary anti-Pnc IgG, IgA, IgA1, and IgA2 antibodies to serotypes 6B, 14, 19F, and 23F were measured in both groups at the age of 7 and 13 months.
Results
Salivary anti-Pnc IgG and IgA were detected more often in the PncOMPC than in the control group. However, the difference between groups was significant only for 19F and 23F IgA concentrations at the age of 7 months. At the age of 13 months, antibody concentrations did not differ between PncOMPC and control groups. The rises in IgA concentrations between 7 and 13 months of age were mainly of subclass IgA1. Further, there is a clear trend that PncPS booster induces higher salivary anti-Pnc PS antibody concentrations than the PncOMPC.
Conclusion
We found that PncOMPC can induce a mucosal IgA response. However, the actual impact of mucosal antibodies in protection against pneumococcal infections is not clear.
BMC Infectious Diseases. 01/2005;
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ABSTRACT: Surface associated pneumococcal proteins alpha-enolase (Eno), immunoglobulin A1 protease (Iga), streptococcal lipoprotein rotamase A (SlrA), and putative proteinase maturation protein A (PpmA) have potential as candidates for future protein-based anti-pneumococcal vaccines. The immunogenicity of these proteins were studied in a cohort of 329 children during their first two years of life. During the first recorded episode of otitis media, acute and convalescent phase sera were available from 151 children. Concentrations of antibodies against Eno, Iga, SlrA and PpmA were measured by EIA and detected in 99% (300/302), 95% (288/302), 95% (288/302), and 83% (251/302) of the sera, respectively. There were no statistically significant differences between the groups of children with and without a history of pneumococcal contact or with respect to the type of pneumococcal contact. Despite a mean overall decrease in the antibody titers in the convalescent sera following AOM, several children were able to respond with a more than twofold increase in antibody titer in response to AOM. The majority of the children with increased antibody concentrations appeared in the groups, which were colonized with pneumococci at the time of serum collection, but were recorded as having no prior contact with pneumococci. In conclusion, SlrA, PpmA, Eno and Iga are immunogenic proteins that elicit antibody responses early in life. No significant correlation between antibody titers to these proteins and pneumococcal carriage or infection was found. Presumably, this results from the presence of cross-reactive epitopes on commensal bacteria.
Vaccine 08/2004; 22(21-22):2737-42. · 3.77 Impact Factor
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ABSTRACT: To describe the antibody response to pneumococcal capsular polysaccharides in children <2 years of age with pneumococcal acute otitis media (AOM) caused by serotypes 6A, 6B, 11A, 14, 19F or 23F. These serotypes were commonly found in both nasopharyngeal carriage and AOM in children of the study population in Finland.
Serum antibody concentrations to pneumococcal capsular polysaccharides of types 6B, 11A, 14, 19F and 23F were measured by enzyme immunoassay in acute and convalescent sera from children with AOM.
Responses (at least 2-fold increase of antibody concentration) were relatively infrequent and varied with both the age of the child and the serotype of the Streptococcus pneumoniae isolated from the middle ear fluid. Children older than 12 months were more likely to have antibody responses than were younger children. Responses were seen only infrequently to types 6A, 6B or 19F (1 of 14, 1 of 9 and 2 of 25, respectively), more often to types 11A and 14 (2 of 8 and 3 of 8) and relatively frequently to type 23F (8 of 18). However, the convalescent antibody concentrations to type 23F were low and usually declined after the infection, whereas responders to 14 AOM had antibodies that persisted at a high concentration through the follow-up.
The results emphasize the differences between Streptococcus pneumoniae serotypes in their immunogenicity and quantitative and qualitative differences of antibodies produced after infection.
The Pediatric Infectious Disease Journal 03/2002; 21(3):186-92. · 3.58 Impact Factor
