title: Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.
abstract: The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects.
  
  
  CONCLUSIONS
  The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.
authors.affiliation: Children's Hospital, Johannes Gutenberg University, Mainz, Germany. zepp@mzdmza.zdv.uni-mainz.de
authors.forename: F
authors.initials: F
authors.lastname: Zepp
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmitt
authors.forename: A
authors.initials: A
authors.lastname: Kaufhold
authors.forename: A
authors.initials: A
authors.lastname: Schuind
authors.forename: M
authors.initials: M
authors.lastname: Knuf
authors.forename: P
authors.initials: P
authors.lastname: Habermehl
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: H
authors.initials: H
authors.lastname: Bogaerts
authors.forename: M
authors.initials: M
authors.lastname: Slaoui
authors.forename: R
authors.initials: R
authors.lastname: Clemens
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000917:Antibody Formation / Q000276:immunology; D003429:Cross Reactions; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate