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PMID: 3516876 Published · ppublish English Journal Article

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

Infection and immunity ·Vol. 52 ·No. 2 ·1986-05-00 ·Pages 519-28

Schneerson R, Robbins JB, Parke JC, Bell C, Schlesselman JJ, Sutton A, Wang Z, Schiffman G, Karpas A, Shiloach J

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 preexisting 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 50- or 100-micrograms 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.

MeSH Terms
Adjuvants, Immunologic Adult Aluminum Hydroxide/immunology Animals Antibodies, Bacterial/biosynthesis,classification Antigens, Bacterial/administration & dosage Cross Reactions Escherichia coli/immunology Haemophilus influenzae/immunology Humans Macaca mulatta Polysaccharides, Bacterial/immunology Streptococcus pneumoniae/immunology Tetanus Toxoid/immunology
Chemicals
Adjuvants, Immunologic Antibodies, Bacterial Antigens, Bacterial Polysaccharides, Bacterial Tetanus Toxoid Aluminum Hydroxide
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Schneerson R
Robbins J B
Parke J C
Bell C
Schlesselman J J
Sutton A
Wang Z
Schiffman G
Karpas A
Shiloach J
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.52.2.519-528.1986
Published
1986-05-00
Pages
519-28
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC261031
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.52.2.519-528.1986 PMC Full Text View journal details
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