Response to Pneumococcal Immunization in Children with and Without Recurrent Infections

Abstract

Many children with recurrent sinopulmonary infections fail to mount an adequate humoral response following immunization with polysaccharide antigens. At present there are no controlled studies comparing responses to pneumococcal immunization in children with recurrent infections and a healthy, age-matched cohort. Immunological evaluation was performed on 66 children with recurrent sinopulmonary infections, aged 2-5 years (mean 3.06 +/- 0.92). A control group included 28 healthy, age-matched controls (mean 3.14 +/- 0.88 years). Both groups were immunized with 23 valent pneumococcal vaccine, and titers were measured before and 4 weeks after immunization. Antibody levels to 12 pneumococcal serotypes were measured via radioimmunoassay. Geometric preimmunization mean titers in the control group were 215.5 +/- 157 ngAbN/ml rising to 989.5 +/- 745 ngAbN/ml compared to 77.71 +/- 38.4 ngAbN/ml increasing to 446.7 +/- 406 ngAbN/ml in the study group (p < .05). Serotypes 3, 4, 7F, 8, 9N, and 18C were the most immunogenic, while serotypes 6A and 14 were the least. Overall, the control group responded to 7.71 +/- 1.24 serotypes versus 5.1 +/- 2.0 in the study group (p < .05), where postimmunization titers at least doubled and rose to > or = 300 ngAbN/ml. All controls responded to at least five or more serotypes, 26/28 responded to 6 or more. In contrast, only 38/66 (57%) of study patients responded to five or more serotypes, and only 27/66 (41%) responded to at least 6 of 12. Preimmunization titers of greater than 300 ngAbN/ml were present in 30% (102/336) of the control serotypes; however, only 53 of these (52%) doubled post immunization; 22% of the elevated titers decreased post immunization. Markedly elevated titers > or = 500 ngAbN/ml were present in 20% (69/336) of the preimmunization serotypes, only 39% of these doubled post immunization. Twenty-three valent pneumococcal vaccine is immunogenic in young, healthy children. A significant percentage of children with recurrent sinopulmonary infections fail to produce adequate serotype specific antibodies following pneumococcal immunization.

Clinical correlates of response to pneumococcal immunization

“…We chose criteria that make reference to both an absolute antibody level and fold change, at the same time acknowledging that responses to wild-type antigens, as evidenced by elevated initial titres, are also evidence of an ability to respond. 9,36 The minimum antibody level chosen to define a response represents 20% of that found for each serotype in a reference pool and has been used in a previous ELISA-based study of pneumococcal antibody response. 36 A limitation of the present study is its small sample size and attendant increased risk of type II error.…”

“…Factors complicating the definition of the normal antibody response to polysaccharide antigens are its variation with age, 8–;10 the differing prevalence of serotypes in different populations, and variation in the immunogenicity of individual serotypes. There is a lack of prospectively collected data on the responses of healthy children to pneumococcal immunization by age and serotype, 6 which has resulted in the use of essentially arbitrary criteria relating to either a predefined titre 11–;13 or a combination of titre and degree of change in antibody levels (fold change) following immunization that varies between studies 9,10,14,15 . Additional interstudy variables include the method of antibody assay (radioimmunoassay (RIA) versus enzyme linked immunosorbent assay (ELISA)), and the number and specificity of the serotypes assayed.…”

“…Part of this uncertainty arises from the fact that the normal antibody responses of children to pneumococcal antigens are still being defined. 1,6 Factors complicating the definition of the normal antibody response to polysaccharide antigens are its variation with age, [8][9][10] the differing prevalence of serotypes in different populations, and variation in the immunogenicity of individual serotypes. There is a lack of prospectively collected data on the responses of healthy children to pneumococcal immunization by age and serotype, 6 which has resulted in the use of essentially arbitrary criteria relating to either a predefined titre [11][12][13] or a combination of titre and degree of change in antibody levels (fold change) following immunization that varies between studies.…”

Fatores de risco e medidas profiláticas nas pneumonias adquiridas na comunidade

“…Silk et al (99) fizeram estudo controlado, comparando a resposta da imunização pneumocócica em crianças com infecção recorrente e em grupo controle saudável da mesma idade. Ambos os grupos foram imunizados com a vacina pneumocócica, sendo os títulos de anticorpos medidos antes e após quatro semanas da imunização.…”

Avaliação da resposta humoral à vacina pneumocócica conjugada 7-valente em crianças com asma moderada em uso de corticóide inalatório e em crianças com fibrose cística

“…O efeito dessa vacina sobre a colonização de nasofaringe é importante, bem como em relação à resistência dos pneumococos (Dagan, 2009). Os estudos mostram maior imunogenicidade dessa vacina (Black et al, 2000 (Silk et al, 1998;Landesman et al, 1983;Sorensen et al, 1996) anos, e a população adulta era em torno de 10% (Yankaskas et al, 2004). (Wong et al, 1984;Malfroot et al, 2005).…”