Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults

doi:10.1016/j.vaccine.2003.07.020

Vaccine

Volume 22, Issues 3–4, 2 January 2004, Pages 511-519

https://doi.org/10.1016/j.vaccine.2003.07.020 Get rights and content

Abstract

New-borns raise limited antibody responses to most T cell-dependent antigens but little is known about neonatal T lymphocyte responses to vaccines. In this study, we compared the immune response induced by the hepatitis B vaccine in new-borns and naı̈ve adults. Infants produced markedly higher serum anti-hepatitis B surface (HBs) antibody titres than adults. This was not associated with greater HBs Ag-specific Th2 cytokine responses but with lower primary IFN-γ responses. At 1 year, the infant memory response to HBs Ag was characterised by higher Th2 responses than those of adults. We conclude that neonatal antibody and T cell responses to hepatitis B vaccine differ from those induced in adults.

Introduction

Neonatal immunisation is required to protect infants from pathogens, but the responses are limited by the immaturity of the neonatal immune system. Young infants have defective antibody responses to both T cell-independent and -dependent antigens [1], [2]. This immaturity prevents the administration of most childhood vaccines until several weeks or months after birth. Very little is known about T cell responses to vaccines in young infants [1], [2], [3]. Data obtained in animals also indicate that neonatal T lymphocyte responses are affected for new-born mice have defective Th1 responses to vaccines and preferentially produce Th2 cytokines either early or during the memory phase of the immune response [4], [5], [6], [7], [8]. Recent data showing that human cord blood-derived dendritic cells are defective in the production of IL-12, a cytokine playing a central role in the differentiation of Th1 lymphocytes, also suggest that type 1 responses could be defective in human new-borns [9], [10]. However, this observation was not reproduced in another recent study [11]. We recently reported that human new-borns have defective IFN-γ responses to oral polio vaccine (OPV) [12]. In contrast, we observed that BCG vaccination induces a potent Th1 type immune response at birth in humans as in mice [4], [13], [14]. This could be related to the potent APC-activating properties of BCG and/or to its persistence during the maturation of the immune system.

Neonatal hepatitis B vaccination is part of the immunisation programme of many countries, both in the industrialised and developing world [15]. Hepatitis B vaccines are composed of highly purified preparations of hepatitis B surface (HBs) Ag obtained from the plasma of patients with chronic infection (plasma-derived vaccine) or from yeast or mammalian cells transfected with viral DNA (recombinant vaccine). Despite the immaturity of the neonatal immune system, hepatitis B vaccine induces a vigorous antibody response in early life [15]. This response correlates with the protective efficacy of hepatitis B vaccine against vertical transmission of the virus from mothers [15]. Although vaccine-induced neutralising antibodies play an important role in protecting young infants from infection, the control of viral replication also involves helper T lymphocytes [16]. In adults and older children, hepatitis B vaccine activates HBs Ag-specific T cells producing both type 1 and 2 cytokines [17], [18], [19]. The T cell response to hepatitis B vaccine in young infants has not yet been reported.

This study was undertaken to compare the T lymphocyte response to neonatal and adult hepatitis B immunisation. The immune response to recombinant hepatitis B vaccine was measured in infants immunised at birth, 2 and 4 months of age. Memory responses were measured before and after booster immunisation at 1 year of age. These responses were compared to those measured in naı̈ve adults, identified by lack of serological evidence of previous exposure to hepatitis B virus (HBV), who were vaccinated following the same schedule. As we previously observed that BCG vaccination markedly increases the primary immune response to hepatitis B vaccine in new-borns [20], we also assessed the influence of BCG on infant memory responses.

Section snippets

Study population

This prospective study was approved by the Gambia Government/Medical Research Council (MRC) Ethics Committee. Informed consent was obtained from adults and mothers of infants. Infants included in this study had been enrolled in a randomised trial on the effect of BCG vaccination on the immune response to unrelated vaccines [20]. Briefly, babies were recruited at birth and randomly allocated to one of three study groups receiving BCG at birth, 2 or 4.5 months of age. Infants who had received BCG

Infants have a higher primary antibody response to hepatitis B vaccine than adults

Before administration of hepatitis B vaccine, anti-HBs antibodies were detected in some infants reflecting passive transfer of maternal antibodies (Fig. 1). In both adults and infants, as expected, immunisation with three doses of hepatitis B vaccine induced a significant increase in anti-HBs antibody concentrations (P<0.0001). This increase was more marked in infants than in adults: the difference being significant after a single dose of hepatitis B vaccine (P<0.0001), and most marked

Discussion

This study demonstrates that the immune response to hepatitis B vaccine is different in new-borns and adults. Infants had markedly higher primary and memory antibody responses to hepatitis B vaccine than adults. In contrast, their capacity to produce IFN-γ was lower during the primary phase of the response, which was not associated with an increased production of type 2 cytokines. However, during the memory response to HBs Ag they produced more of type 2 cytokines than adults.

The high antibody

Acknowledgements

We are particularly grateful to Drs. Beryl West and Matthew Shaw for allowing us to use sera obtained from adults enrolled in Gambia Government/MRC STD study. We thank Paolo Valenti, Gianna Cadau, Adam Jeng and Maimuna Mendy for excellent technical assistance in the laboratory, and Sulayman Manjang and Alpha Jawo for excellent field work. We thank Clothilde Thiriart and Martine Wettendorff, Glaxo SmithKline Biologicals, Belgium, for providing vaccines and vaccine antigens for the in vitro

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Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults

Abstract

Introduction

Section snippets

Study population

Infants have a higher primary antibody response to hepatitis B vaccine than adults

Discussion

Acknowledgements

Vaccine

Immunol. Today

Hepathology

Gastroenterology

Am. J. Prev. Med.

Vaccine

Vaccine

Prevention of infectious diseases by neonatal and early infantile immunisation: prospect for the new millennium

Curr. Opin. Infect. Dis.

Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: predominance of a Th2-biased pattern which persists after adult boosting

Eur. J. Immunol.

Partial correction of the TH2/TH1 imbalance in neonatal immune responses to vaccine antigens through selective adjuvant effects

Eur. J. Immunol.

Neonatal peptide exposure can prime T cells and, upon subsequent immunization, induce their immune deviation: implications for antibody vs. T cell-mediated autoimmunity

J. Exp. Med.

Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are biased to Th2 secondary responses

J. Immunol.

The generation of Th memory in neonates versus adults: prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates

J. Immunol.

Deficient IL-12 (p35) gene expression by dendritic cells derived from neonatal monocytes

J. Immunol.

Neonatal dendritic cells are intrinsically biased against Th-1 immune responses

Clin. Exp. Immunol.

Development of interleukin-12-producing capacity throughout childhood

Infect. Immun.

T cell responses to vaccines in infants: defective IFN-γ production after oral polio vaccination

Clin. Exp. Immunol.