Covalent binding to immunogenic proteins increases the immunogenicity of the capsular polysaccharides of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A). Conjugates composed of Hib, Pn6A, or the cross-reacting Escherichia coli K100 covalently bound to tetanus toxoid (TT) were injected into young adult volunteers. Local reactions were common and were probably due to Arthus reactivity mediated by the preexisiting antibodies reacting with the TT component of the conjugates. Fever occurred in about 10% of the volunteers after the first injection; no volunteers had fever after the second injection. Similar levels of Hib or Pn6A antibodies were elicited by either 50or 100-,Ig doses or by concurrent injection of two different conjugates (Hib-TT and Pn6A-TT or Hib-TT and K100-TT). The Hib-TT elicited about a 180-fold increase in Hib antibodies, and the Pn6A-TT conjugate elicited about an 8-fold increase in Pn6A antibodies after one injection. Booster reactions were not elicited in adults; similar levels of antibodies in the five experimental groups suggested that the responses elicited by the conjugates were maximal. A one-way cross-reaction was noted as Pn6A conjugates elicited rises of Hib antibodies in 13 of 20 volunteers; only 4 of 59 volunteers immunized with Hib-TT had increases in Pn6A antibodies. The preimmunization Hib antibodies were composed of immunoglobulin M (IgM), IgA, and IgG. The postimmunization sera showed an increase in all three isotypes; the elevation of the IgG was the highest of the three isotypes. Conjugate-induced antibodies to both the polysaccharide and TT exerted biological activities that have been correlated with immunity. Adsorption of the Hib-TT onto aluminium hydroxide resulted in higher levels and an earlier Hib antibody response in infant rhesus. These results encourage the evaluation of Hib and Pn6A conjugates in human children and infants.
Escherichia coli O157 causes severe enteritis and the extraintestinal complication hemolytic-uremic syndrome. Serum IgG against the surface polysaccharide antigen, the O-specific polysaccharide of lipopolysaccharide (LPS), may confer protective immunity by lysing the inocula. In a phase 1 clinical study, three investigational vaccines were studied in 87 healthy adults. The vaccines were prepared by covalently binding E. coli O157 O-specific polysaccharide with Pseudomonas aeruginosa recombinant exoprotein A. No significant reactions were reported. Most volunteers (81%) responded with a > 4-fold increase in IgG LPS antibodies 1 week after vaccination; all volunteers responded with a > 4-fold rise at 4 weeks and this level was sustained for 26 weeks after injection. All three vaccines elicited high titers of serum bactericidal activity that roughly correlated with the serum IgG and IgM LPS antibody levels. A phase 2 study in young children is planned.
Supernumerary isochromosomes resulting in autosomal tetrasomy are rare and have been described only for 12p, 18p, and 9p. Nineteen previous cases of tetrasomy 9p have been reported, and in 6 cases, tissue-specific mosaicism was implied with the i(9p) cell line present exclusively or predominantly in blood. We report on an infant who had apparently normal chromosomes (46,XY) on CVS. He was referred for genetic evaluation because of mild developmental delay and minor anomalies. In 75% of blood cells he had an extra isodicentric 9p chromosome (pter-->q12-->pter). The interpretation of tetrasomy 9p was confirmed by elevated GALT activity. No tetrasomy 9p cells were seen in 100 skin fibroblasts. This case demonstrates the tissue specific mosaicism in tetrasomy 9p which rendered the anomaly undetectable by CVS. It also demonstrates the mild end of the clinical spectrum associated with tetrasomy 9p.
Approximately 16,000 children, from two months to five years of age, were vaccinated with the capsular polysaccharide of either Haemophilus influenzae type b or group C Neisseria meningitidis. Immunizations were carried out in a double-masked, randomized manner; the doses of immunogens used were 10 microgram of H. influenzae type b polysaccharide and 25 micron g of the group CN. meningitidis polysaccharide. Immunogenicity of the two vaccines was measured in single, random specimens of blood taken from vaccinees of all ages at various intervals after immunization. A positive effect on formation of serum antibody was observed in children of all ages vaccinated with N. meningitidis polysaccharide, but increased levels of serum antibody to H. influenzae type b were observed only in recipients of that vaccine who were three years of age or older. No untoward reactions to either vaccine were noted, and both vaccines retained their original molecular size after storage for three years. Too few cases of disease have been studied for a definitive assessment of vaccine efficacy; however, a slightly protective effect against meningitis was observed for the H. influenzae type b vaccine in infants up to one year of age.
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