Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates

Abstract

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.

Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide–tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections

“…Complement-dependent antibody-mediated bactericidal assay. As observed in healthy subjects [9], there was a good correlation between bactericidal activity of the patients' sera and post-immunization HibCP antibody levels measured by RIA. Eight out of 12 patients showed more than a 10-fold increment in the bactericidal assay and were also positive in RIA.…”

“…Radioimmunoassay. Seventeen out of 21 patients showed an antibody response similar to that observed in healthy adults [9]. One patient (no.…”

“…We did not find any correlation between the HibCP and TTspecific antibody responses in these patients. A similar dissociation between the antibody response to the CP and the protein component was elicited by conjugates in laboratory animals and humans [9,18].…”

“…The biological activities of HibCP antibodies were also analysed. Total Hib-specific antibodies and their biological activity were compared with those of normal adults immunized with the same vaccine [9].…”

Immune responses of young mice to pneumococcal type 9V polysaccharide-tetanus toxoid conjugate

“…The weak immune response to PS antigens can be improved by using conjugate vaccines to immunize mothers and/or young children (37,46). The immunoglobulin G (IgG) antibody induced by a conjugate immunogen is transferred through the placental membrane from the mother to the fetus.…”