Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules

Ray Borrow, Ron Dagan, Fred Zepp, Hans Hallander, Jan Poolman

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations


Conjugate vaccines using diphtheria toxoid variant (CRM 197), diphtheria toxoid and tetanus toxoid (TT) as carrier protein may induce immune interactions (interference or impairment as measured by lower antibody levels, or enhancement [higher antibody levels]) when coadministered with other vaccines. Immune enhancement occurs when two TT conjugates are coadministered. CRM 197 conjugate vaccines induce immune bystander interference when given with diphtheria-tetanus-acellular pertussis vaccines, which reduces responses to coadministered Haemophilus influenzae type b vaccine conjugated to TT. These bystander effects are greater as the amount of CRM 197 administered increases. When large amounts of either TT or CRM 197 are coadministered, dose-related carrier-induced epitopic suppression may occur, affecting immune responses to meningococcal or pneumococcal polysaccharides. These observations have implications for vaccine scheduling. The range of available alternative vaccines means that specific vaccine coadministrations can avoid or reduce CRM 197-induced interference. Potential interactions arising from new CRM 197 or TT conjugates will need to be thoroughly examined.

Original languageEnglish
Pages (from-to)1621-1631
Number of pages11
JournalExpert Review of Vaccines
Issue number11
StatePublished - 1 Nov 2011
Externally publishedYes


  • CRM
  • Haemophilus influenzae type b
  • carrier-induced epitopic suppression
  • conjugate vaccines
  • enhancement
  • hepatitis B
  • interference
  • meningococcal vaccine
  • pneumococcal vaccine

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery


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