Hyporesponsiveness and its clinical implications after vaccination with polysaccharide or glycoconjugate vaccines

Abstract

Hyporesponsiveness (immune tolerance) follows vaccination with meningococcal polysaccharide and many pneumococcal polysaccharide serotypes. Hyporesponsiveness after Haemophilus influenzae type b polysaccharide vaccination has not been directly observed, but may follow exposure during disease in some individuals. Use of currently licensed conjugate vaccines has not been associated with hyporesponsiveness to date, with the possible exception of pneumococcal serotype 3. Introduction of polysaccharide vaccines anywhere into a conjugate vaccination schedule may result in reduced immune responses on subsequent exposure. This review of vaccine-induced hyporesponsiveness and its potential clinical implications considers recent evidence suggesting that hyporesponsiveness may occur for specific components of combined conjugate vaccines, such as pneumococcal serotype 3. These data have implications for the development of new multivalent vaccines.

Keywords::

• conjugate vaccines
• hyporesponsiveness
• immune tolerance
• vaccination

Acknowledgements

The authors are indebted to Dan Granoff for donating Figure 6. The authors thank Joanne Wolter and Ulrike Krause for assistance in preparation of the manuscript.

Financial & competing interests disclosure

Jan Poolman is an employee of GlaxoSmithKline Biologicals. Ray Borrow has received assistance to attend scientific meetings from Pfizer, Novartis, Sanofi Pasteur and Baxter Bioscience and has served as an ad hoc consultant for Pfizer, GlaxoSmithKline Biologicals, Novartis, Sanofi Pasteur and Baxter Bioscience. Industry honoraria received for consulting, lecturing and writing are paid directly into Central Manchester and Manchester Children’s University Hospitals NHS Trust endowment fund. Ray Borrow has performed contract research on behalf of the Health Protection Agency (funded by Pfizer, Novartis, Baxter Bioscience, GlaxoSmithKline Biologicals and Sanofi Pasteur). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Joanne Wolter assisted in writing the first draft of the manuscript. Funding for this assistance was provided by GlaxoSmithKline Biologicals.