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Characterization of the Serum Antibody Response to the Capsular Polysaccharide of Haemophilus influenzae Type b in Children with Invasive Infections Birger Trollfors, Teresa Lagergard, Bo A. Claesson, Eva Thornberg, Jeanette Martinell, and Rachel Schneerson
Departments ofPediatrics, Infectious Diseases, Pediatric Anaesthesia and Intensive Care, and Medical Microbiology and Immunology, University of Giiteborg, Sweden; Laboratory of Developmental and Molecular Immunity, National Institute ofChild Health and Human Development, National Institutes ofHealth, Bethesda, Maryland
The human serum antibody response to the capsular polysaccharide (CPS) of Haemophilus influenzae type b (Hib) is age dependent [1-5]. Young children have a poor response after both invasive infection and vaccination with the purified CPS. The age below which no antibody response can be detected differs according to different studies from 6 to 24 months [1-5]. This may be a result of the differing sensitivities of the methods used to detect serum antibodies, different intervals between infection or vaccination and serum sampling, and genetic differences between populations studied. In older children and adults, increases are usually seen in all three antibody classes (IgG, IgM, and IgA) [1,2,4,6], but in these age groups also there is a high proportion of nonresponders [4]. Opinions differ concerning the subclass composition of the IgG response to CPS antigens. A commonly held opinion has been that this response is restricted to the IgG2 subclass [7-9], but other studies have shown a mixed IgG I and IgG2 response with predominance of IgG 1 antibodies [10-16], The aim of this study was to characterize the antibody
Received 30 March 1992; revised 16 July 1992, Informed consent was obtained from the parents ofal! participating children. The study was approved by the Ethics Committee of the University of Goteborg. Financial support: Swedish Society ofMedicine, Goteborg Society ofMedicine. Reprints or correspondence: Dr. Birger Trollfors, Department ofPediatrics, East Hospital. S-416 85 Goteborg, Sweden. The Journal of Infectious Diseases 1992;166:1335-9 © 1992 by The University of Chicago. All rightsreserved. 0022-1899/92/6606-0019$01.00
response including the class and IgG subclass composition to Hib CPS after invasive infections in a series of serum samples obtained 6- I2 months after the onset of symptoms.
Patients and Methods A first serum sample was obtained as early as possible from all children hospitalized with a suspicion of bacterial meningitis or acute epiglottitis at the Departments ofPediatrics and Infectious Diseases, East Hospital, Goteborg, If Hib was isolated from the blood or cerebrospinal fluid (CSF), a second serum sample was obtained on the last day of intravenous treatment (epiglottitis,S days; meningitis, 10 days), a third sample 4-6 weeks after onset of symptoms, and a fourth sample 6- I2 months after onset of symptoms, Thirty children, 18 boys and 12 girls, were included. Their ages ranged from 2 days to 5 years; 17 had meningitis and 12 epiglottitis. One child was a full-term neonate who developed Hib septicemia during her second day of life. Of the children, 28 were ethnic Swedes, I child was of non-Swedish origin, and I child had one Swedish and one non-Swedish parent. Hib was isolated from both blood and CSF in IS, from blood alone in 13, and from CSF alone in 2 children. None of the children had had any serious disease before onset of the Hib infection, and all were healthy during the follow-up period of 6-12 months. According to the protocol, 4 serum samples each were to be obtained, From 6 children, only 3 samples could be obtained; thus, the total for the study was 114. Total serum antibodies against Hib CPS were determined in duplicate by RIA [17]. IgG, IgM, and IgA antibodies were determined by direct ELISA [16, 18]. Antibodies of the four IgG subclasses were determined by indirect ELISA using murine monoclonal antibodies [15, 16]. The results obtained by direct
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 6, 2015
The serum antibody response to the capsular polysaccharide of Haemophilus infiuenzae type b (Hib) was studied in 30 children aged 1 day-5 years with invasive Hib infections. From each child, serum was obtained 0-2 days, 5-11 days, 1 month, and 6-12 months after onset ofsymptoms. Total antibodies were determined with RIA and isotypes with ELISA. Only 2 children had antibody levels above the estimated protective level (0.15 #gjmL) in the first serum sample. The antibody response was age dependent with wide individual variations. Children ;;;,2 years had increases in IgG, IgM, and IgA antibodies with predominance of IgG. The initial IgG response was IgGI and IgG2 with predominance ofIgGl. In the last serum sample, IgGI antibodies had decreased while IgG2 antibodies remained unchanged, Only 2 of7 children
Characterization of the Serum Antibody Response to the Capsular Polysaccharide of Haemophilus influenzae Type b in Children with Invasive Infections Birger Trollfors, Teresa Lagergard, Bo A. Claesson, Eva Thornberg, Jeanette Martinell, and Rachel Schneerson
Departments ofPediatrics, Infectious Diseases, Pediatric Anaesthesia and Intensive Care, and Medical Microbiology and Immunology, University of Giiteborg, Sweden; Laboratory of Developmental and Molecular Immunity, National Institute ofChild Health and Human Development, National Institutes ofHealth, Bethesda, Maryland
The human serum antibody response to the capsular polysaccharide (CPS) of Haemophilus influenzae type b (Hib) is age dependent [1-5]. Young children have a poor response after both invasive infection and vaccination with the purified CPS. The age below which no antibody response can be detected differs according to different studies from 6 to 24 months [1-5]. This may be a result of the differing sensitivities of the methods used to detect serum antibodies, different intervals between infection or vaccination and serum sampling, and genetic differences between populations studied. In older children and adults, increases are usually seen in all three antibody classes (IgG, IgM, and IgA) [1,2,4,6], but in these age groups also there is a high proportion of nonresponders [4]. Opinions differ concerning the subclass composition of the IgG response to CPS antigens. A commonly held opinion has been that this response is restricted to the IgG2 subclass [7-9], but other studies have shown a mixed IgG I and IgG2 response with predominance of IgG 1 antibodies [10-16], The aim of this study was to characterize the antibody
Received 30 March 1992; revised 16 July 1992, Informed consent was obtained from the parents ofal! participating children. The study was approved by the Ethics Committee of the University of Goteborg. Financial support: Swedish Society ofMedicine, Goteborg Society ofMedicine. Reprints or correspondence: Dr. Birger Trollfors, Department ofPediatrics, East Hospital. S-416 85 Goteborg, Sweden. The Journal of Infectious Diseases 1992;166:1335-9 © 1992 by The University of Chicago. All rightsreserved. 0022-1899/92/6606-0019$01.00
response including the class and IgG subclass composition to Hib CPS after invasive infections in a series of serum samples obtained 6- I2 months after the onset of symptoms.
Patients and Methods A first serum sample was obtained as early as possible from all children hospitalized with a suspicion of bacterial meningitis or acute epiglottitis at the Departments ofPediatrics and Infectious Diseases, East Hospital, Goteborg, If Hib was isolated from the blood or cerebrospinal fluid (CSF), a second serum sample was obtained on the last day of intravenous treatment (epiglottitis,S days; meningitis, 10 days), a third sample 4-6 weeks after onset of symptoms, and a fourth sample 6- I2 months after onset of symptoms, Thirty children, 18 boys and 12 girls, were included. Their ages ranged from 2 days to 5 years; 17 had meningitis and 12 epiglottitis. One child was a full-term neonate who developed Hib septicemia during her second day of life. Of the children, 28 were ethnic Swedes, I child was of non-Swedish origin, and I child had one Swedish and one non-Swedish parent. Hib was isolated from both blood and CSF in IS, from blood alone in 13, and from CSF alone in 2 children. None of the children had had any serious disease before onset of the Hib infection, and all were healthy during the follow-up period of 6-12 months. According to the protocol, 4 serum samples each were to be obtained, From 6 children, only 3 samples could be obtained; thus, the total for the study was 114. Total serum antibodies against Hib CPS were determined in duplicate by RIA [17]. IgG, IgM, and IgA antibodies were determined by direct ELISA [16, 18]. Antibodies of the four IgG subclasses were determined by indirect ELISA using murine monoclonal antibodies [15, 16]. The results obtained by direct
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 6, 2015
The serum antibody response to the capsular polysaccharide of Haemophilus infiuenzae type b (Hib) was studied in 30 children aged 1 day-5 years with invasive Hib infections. From each child, serum was obtained 0-2 days, 5-11 days, 1 month, and 6-12 months after onset ofsymptoms. Total antibodies were determined with RIA and isotypes with ELISA. Only 2 children had antibody levels above the estimated protective level (0.15 #gjmL) in the first serum sample. The antibody response was age dependent with wide individual variations. Children ;;;,2 years had increases in IgG, IgM, and IgA antibodies with predominance of IgG. The initial IgG response was IgGI and IgG2 with predominance ofIgGl. In the last serum sample, IgGI antibodies had decreased while IgG2 antibodies remained unchanged, Only 2 of7 children
