Elsevier

Vaccine

Volume 25, Issue 8, 9 February 2007, Pages 1497-1502
Vaccine

Breastfeeding enhances the antibody response to Hib and Pneumococcal serotype 6B and 14 after vaccination with conjugate vaccines

https://doi.org/10.1016/j.vaccine.2006.10.025Get rights and content

Abstract

Background

This study was performed in order to investigate the relationship between breastfeeding and the antibody response after vaccination with conjugate vaccines against Hib and pneumococcal diseases.

Methods

This was an open non-randomised multi-centre study enrolling 101 healthy Swedish infants. PncCRM was administered concomitantly with DTaP/IPV/Hib at 3, 5, and 12 months at separate site. Duration of breastfeeding was calculated for days of almost exclusive as well as of total (any form of) breastfeeding.

Results

At 13 months of age 6 out of 83 children did not reach 0.2 μg/ml against serotype 6B, and five of these were breastfed less than 90 days (Fisher's Exact test, P = 0.011). Four children did not reach 1 μg/ml against Hib and all those were breastfed less than 90 days (Fisher's Exact test, P = 0.008). One month after the second dose, at 6 months of age, children breastfed 90 days or more showed significantly higher GMC against serotype 14 (P = 0.003).

Conclusion

This study indicates that children exclusively breastfed 90 days or more might get a better serological protection against Hib, and the pneumococcal serotypes 6B and 14 after vaccination, compared to children less breastfed.

Introduction

Immunization is a very effective preventive strategy. The incidence of invasive Haemophilus influenza type b (Hib) disease has decreased rapidly after introduction of general Hib immunization [1]. However, an increase in invasive Hib disease has been reported in the UK in children 1–4 years old associated with waning immunity against Hib. Lack of a booster vaccination, loss of natural boosting by less Hib carriage and herd-immunity, as well as a change from a whole-cell Pertussis to an acellular Pertussis combo-vaccine have been suggested causes [2], [3], [4]. Besides these factors a low breastfeeding-rate in the UK population might be a neglected contributing factor [5].

Invasive pneumococcal disease (IPD) is a threat to infants and young children, especially in low-income countries, with a high mortality rate. In the U.S. this situation has rapidly changed after extensive immunization with a heptavalent pneumococcal conjugate vaccine against serotype 4, 6B, 9V, 14, 18C, 19F and 23F in childhood and a reduction of IPD is now documented not only in early ages but also in adults 20–39 years and >65 years [6], [7]. This vaccine was given to infants at 2, 4, 6 and 12–15 months of age.

In the Nordic countries and Italy the routine schedule for vaccinations in infancy against Diphtheria, Tetanus, Pertussis, Polio and Hib consists of 3-doses given at 3, 5, and 11–12 months of age. PCV7 given in this 3-dose schedule is as good as the 4-dose U.S. schedule except for a slightly lower protection against serotype 6B and 23F with the 3-dose schedule [8], [9].

A protective effect by breastfeeding against morbidity, and especially against infections, is well established [10]. Breast-milk may have a direct and local effect on the mucosal membranes mainly through secretory-IgA, but also by a long lasting effect through priming of the infant's immune system [10], [11]. A protective effect by breastfeeding on invasive Hib disease is well documented [12], [13], [14], [15]. In previous epidemiological studies, we have found a decreased risk for invasive Haemophilus influenza infection with 5% for each week of added exclusive breastfeeding [15]. The IgG2 anti-Hib response in children 18 months or older with invasive Hib disease is enhanced by breastfeeding with anti-Hib titres 2.5 times higher in children exclusively breastfed for 13 weeks or more than those breastfed less [16]. A stimulatory effect of breastfeeding on the antibody response to Hib after Hib immunization has been documented [17], [18]. Formula fortified with an amount of nucleotides similar to human milk enhanced the Hib and diphtheria antibody response [19]. Immune-phenotypic differences between breast-fed and formula-fed infants indicate a greater maturity in development of the immune system of breastfed infants [20], [21].

The aim of this study was to analyse the antibody concentrations to each of the Pneumococcal serotypes as well as to Hib in relation to the duration of breastfeeding.

Section snippets

Study-base

This was an open non-randomised multi-centre study (Prevenar™ vaccine trial) enrolling 101 healthy Swedish infants at four sites (Malmö, Linköping, Umeå and Örebro). PncCRM was administered concomitantly, but at separate site, with DTaP/IPV/Hib at 3, 5, and 12 months. Antibody concentrations were determined at National Institute of Public Health, KTL, in Finland by EIA for anti-Pneumococcal IgG from serum samples taken at 3, 6, 12 and 13 months, and for anti-Hib IgG from serum samples at 6 and

Results

One hundred and one (101) children were included in the vaccine trial. Two children did not complete the study, one because of serious adverse event and one at the request of the parents. Eighty-three were included in this study after exclusion for different reasons; two infants had no blood samples drawn, three infants did not follow the given time windows for blood sampling and 12 infants did not follow the schedule for vaccination. There were missing data on any breastfeeding for four

Discussion

Our understanding of the development of immunity in infancy and the role of breastfeeding is not fully understood. However, this study indicates that breastfeeding enhances the antibody response to some extent against Hib and the pneumococcal polysaccharides of serotype 6B and 14 after vaccinations with conjugate-vaccines.

Acknowledgments

We wish to thank the children and their parents who have participated in this study, the personnel at the Prevenar study sites in Linköping (Lennart Nilssson, Lena Lindell, Christina Helander), Malmö (Carl-Erik Flodmark, Liselotte Andersson), Umeå (Leif Gothefors, Margareta Bäckman), and Örebro (Laila Fjällryd), the personnel at National Institute of Public Health, KTL, in Helsinki, Finland (Teija Jaakola, Anne Holm, Helena Käyhty and Heidi Åhman), the Research Committee of Örebro County

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