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Genetic regulation of immune responses to vaccines in early life

Genes & Immunity volume 5, pages 122–129 (2004)Cite this article

Abstract

Infant immunization is the most cost-effective strategy to prevent infectious diseases in childhood, but is limited by immaturity of the immune system. To define strategies to improve vaccine immunogenicity in early life, the role of genetic and environmental factors in the control of vaccine responses in infant twins was studied. Immune responses to BCG, polio, hepatitis B, diphtheria, pertussis and tetanus vaccines were measured at 5 months of age in 207 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variation in responses. High heritability was observed for antibody (Ab) responses to hepatitis B (77%), oral polio (60%), tetanus (44%) and diphtheria (49%) vaccines. Significant heritability was also observed for interferon-γ and interleukin-13 responses to tetanus, pertussis and some BCG vaccine antigens (39–65%). Non-HLA genes played a dominant role in responses to Ab-inducing vaccines, whereas responses to BCG were predominantly controlled by genes within the HLA class II locus. Genetic factors, particularly non-HLA genes, significantly modulate immune responses to infant vaccination. The identification of the specific genes involved will provide new targets for the development of vaccines and adjuvants for young infants that work independently of HLA.

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Acknowledgements

We thank the staff of the three enrolment centres and all the twin families for their participation: to Omar Badjie, Dawda Baldeh, Isatou Drammeh, Malick John, Bunja Kebbeh, Suleyman Manjang, Mamadi Sidibeh and Samba Sowe for expert assistance with field work; to Dr Tumani Corrah for help with clinical care of infants; to Dr Mariama Jallow (RVH, Banjul) and Mr JS Saidykhan (Divisional Health Team, Western Kanifing, The Gambia) for guidance during the planning of this project; to Momodou Jobe and Momodou Cham for sample processing, Albert Magnusen, Mariamma Sanneh and Dr Michael Kidd for assistance with antibody assays; to Helen Rance and Sarah Nutland for assistance with HLA typing; to Drs Kris Huygen and Peter Andersen, and to Glaxo SmithKline Biologicals for generously providing antigens; and to Drs Karen Butterworth and Giorgio Sirugo for their contribution to this and ongoing studies in this cohort.

Author information

Author notes

  1. Members listed at the end of the paper

  2. Financial disclosures: A Marchant received research support from Glaxo SmithKline Biologicals. C-A Siegrist has served as consultant and received research support from Glaxo SmithKline Biologicals, Aventis and Wyeth.

Authors and Affiliations

  1. Department of Medicine, University of Cambridge, UK

    M J Newport

  2. University Department of Paediatrics, John Radcliffe Hospital, Oxford, UK

    T Goetghebuer

  3. MRC Tropical Epidemiology Unit, London School of Hygiene and Tropical Medicine, UK

    H A Weiss

  4. Medical Research Council Laboratories, PO Box 273, Banjul, The Gambia

    M J Newport, T Goetghebuer, H Whittle & A Marchant

  5. WHO Collaborative Centre for Neonatal Vaccinology, University of Geneva, Switzerland

    C-A Siegrist

  6. MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    A Marchant

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  1. M J Newport
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  4. H Whittle
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  5. C-A Siegrist
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Consortia

The MRC Gambia Twin Study Group

Corresponding author

Correspondence to M J Newport.

Additional information

This study was supported by the Medical Research Council (UK), the WHO Global Program for Vaccines and Immunization, the Wellcome Trust and the Royal Society.

The MRC Twin Study Group

A Allen, W Banya, D Jackson Sillah, KPWJ McAdam, M Mendy, M Ota, J Vekemans (The Medical Research Council Laboratories, The Gambia); K Jobe (The Gambian Expanded Programme on Immunisation, Department of State for Health, Banjul, The Gambia); S Bennett (the MRC Tropical Epidemiology Unit, London School of Hygiene and Tropical Medicine, UK); P Aaby (the Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark); JC Stockton (Department of Medicine, University of Cambridge, UK); G Cadau, P-H Lambert, S Schlegel-Hauter, P Valenti (the WHO Collaborative Centre for Neonatal Vaccinology, University of Geneva, Switzerland).

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Newport, M., Goetghebuer, T., Weiss, H. et al. Genetic regulation of immune responses to vaccines in early life. Genes Immun 5, 122–129 (2004). https://doi.org/10.1038/sj.gene.6364051

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