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PROTEIN-POLYSACCHARIDE CONJUGATE VACCINE FAILURE

A.J. Pollard, Oxford Vaccine Group

Department of Paediatrics, University of Oxford, Oxford, UK

The introduction of protein-polysaccharide conjugate vaccines to protect young children against

invasive disease caused by Haemophilus influenzae type b (Hib), serogroup C Neisseria meningitidis,

and Streptococcus pneumoniae has led to substantial improvements in child morbidity and mortality

for those countries where the vaccines have been introduced. In addition to the direct protection for

the individual afforded by these vaccines, population exposure to these colonising organisms has

been subtantially reduced leading to herd immunity. Vaccine failure is defined as invasive disease in

an immunised individual and is a rare event in immunised populations. Vaccine failure could result

directly from: storage problems with the vaccine affecting the integrity of the conjugate; incorrect

administration, interaction with coadministered vaccines; or inadequate (gentically determined) host

responses. Other factors which may affect the strength of the vaccine response include the type of

conjugate (e.g. different carrier proteins) and the age of the individual, as immunity wanes rapidly in

early childhood. Another component of vaccine failure may be the loss of natural boosting of immunity

through reduced colonisation.



Booster doses of conjugates can provide protection for those who made poor initial responses and to

maintain protection amongst those whose immunity has waned. Schedules for boosting should

therefore be designed to protect through the period of greatest disease risk. Maintaining protection

against vaccine-preventable invasive bacterial disease to avoid vaccine failure will be a challenge for

child health programmes in the decades to come.



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