Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis in infants and children and a major cause of septicemia, septic arthritis pneumonia and epiglottitis. Pneumococcus type 6A (Pn6A) is a major cause of otitis media and the most frequent type causing meningitis pneumonia. Anticapsular antibodies to these two pathogens are protective; their induction in the young by capsular polysaccharides is hampered by both their age-related immunogenicity and lack of anamestic response. In contrast, conjugates composed of these polysaccharides covalently bound to tetanus toxoid were immunogenic in mice and infant rhesus; this response could be boosted by further injections. Adult volunteers were immunized two times at three week intervals with conjugates composed of Hib, Escherichia coli K100, or Pn6A polysaccharides and tetanus toxoid. Local reactions were common and probably due to Arthus reaction by preexisting tetanus antitoxin. Fever occurred in ten of the recipients after the first injection; in none after the second injection. Hib-TT elicited a 180-fold increase in Hib antibody. Pn6A-TT elicited about an 8-fold increase in Pn6A antibody. Each conjugate induced a 10 to 20-fold increase in TT antibodies. A maximal response occurred in most volunteers after the first injection, with no booster response observed after the second injection. No relation was found between the preimmune levels with the rate of antibody rise or to the side effects of the vaccines. Similar antibody levels were induced by 50 or 100 ug doses and by one conjugate or combination of conjugates. Pre and post-immunization sera had Hib antibodies composed of IgG, IgM, and IgA. Immunization produced the highest response in IgG. Similarly, pre and post-immunization sera were distributed among all IgG subclasses, with the highest response in the IgG2. Pn6A-TT and Hib-TT have been prepared and immunization of 18 month to 2 year old children has begun in Gotenborg, Sweden.
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