Long-term memory immunity against Bordetella pertussis in children 9 years of age who have been vaccinated with acellular pertussis vaccines: effect of an extra preadolescent acellular booster vaccination

Pertussis, or whooping cough, is caused by the bacterium Bordetella pertussis
and is an acute and serious respiratory infection. Since the introduction of
whole-cell pertussis (wP) vaccines in 1953 in the Netherlands, the incidence of
pertussis reduced rapidly. However, despite high vaccination coverage (95%)
pertussis is re-emerging in the Netherlands since 1996. This phenomenon is also
observed in other western countries with high vaccination coverage like
Finland, Germany, the USA, Canada, Australia and Japan. The introduction of an
acellular pertussis (aP) vaccine for children 4 years of age in 2001 in the
Netherlands resulted in a shift of peak prevalence from 4-6 year old children
in 2001 to 8-15 years of age in 2012. Since January 1st 2005, all children are
vaccinated with aP vaccines in the combination vaccine DTaP-IPV-Hib in the
first year of life.
Studies in the US showed a difference in the chance of acquiring pertussis
between children vaccinated with aP or wP. Children vaccinated with aP had
significant more reported pertussis than children who received at least one wP
vaccination. However, our previous *Memory-study* (ISRCTN65428640) showed that
one month after an aP booster vaccination at 4 years of age, children being
primed with wP had significant lower numbers of PT- and Prn-specific memory
B-cells compared with children who have been primed with aP.

The main purpose of this study is to assess the long-term antibody responses
and cellular memory immunity against B. pertussis in a cohort of Dutch
children, 8-9 years of age, who have been vaccinated with aP in the first year
of life. Furthermore, the effects of a second aP booster on humoral- and
cellular memory- immunity one month, one year and six years after booster
vaccination will be investigated in this cohort, since peak-incidence of
pertussis is now highest in children 8-15 years of age. These insights are
necessary to evaluate the current protection against pertussis in this age
group and to understand the possible effects of a second aP booster vaccination
on long-term immunity against pertussis.

Longitudinal intervention study

Participants will receive one injection of DTaP-IPV (Boostrix Polio® (GSK))
combination vaccine intramuscularly in the upper arm as a replacement of the
normal DT-IPV vaccine. Venapunctures will be performed prior to and one month
and one year after vaccination. Six years after vaccination the
participant/parent will perform a fingerprick at home.

Participants will benefit from participating in this study by receiving an
additional pertussis vaccination. From the public health perspective,
participation in this study will contribute to the improvement of the NIP.
Vaccination, venapunctures and vingerprick might be painful and unpleasant,
however, they are relative low risk invasive procedures. On request of the
participant, Xylocaine® spray can be used to reduce possible local pain during
the venapunction. Boostrix Polio® is a registered vaccine in the Netherlands.
Mild adverse reactions to the vaccine may occur but they are expected to be
mainly local and transient. Severe allergic reactions to one of the vaccine
components are unlikely to occur. As a compensation for the vaccination,
venapunctures and the fingerprick, all participants will receive a total of
¤32,50 in vouchers.