Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg− mothers

Cellular & Molecular Immunology volume 7, pages 454–458 (2010)Cite this article

Abstract

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active–passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg+) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg+/HBeAg− mothers. Blood was collected from 46 HBsAg+ mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg+ mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon (IFN)-γ concentrations were determined by ELISA. HBsAg-induced production of IL-2, IL-5, IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination. All neonates were HBsAg− and responded to vaccination. Increased IFN-γ production following HBcAg stimulation was seen in 30.4% of neonates born to HBsAg+/HBeAg− mothers. Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation, whereas IL-5, IL-6 and IL-10 cytokine responses were not significantly different. Almost one-third of uninfected neonates developed viral antigen-induced IFN-γ production, suggesting that they had been exposed to virions or viral derivatives. This encounter, however, did not impair their T-cell responses to vaccination.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Hyams KC . Risks of chronicity following acute hepatitis B virus infection: a review. Clin Infect Dis 1995; 20: 992–1000.

    Article  CAS  Google Scholar 

  2. McMahon BJ, Alward WL, Hall DB, Heyward WL, Bender TR, Francis DP et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985; 151: 599–603.

    Article  CAS  Google Scholar 

  3. Akhter S, Talukder MQ, Bhuiyan N, Chowdhury TA, Islam MN, Begum S . Hepatitis B virus infection in pregnant mothers and its transmission to infants. Indian J Pediatr 1992; 59: 411–415.

    Article  CAS  Google Scholar 

  4. Stevens CE, Beasley RP, Tsui J, Lee WC . Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975; 292: 771–774.

    Article  CAS  Google Scholar 

  5. Lin HH, Lee TY, Chen DS, Sung JL, Ohto H, Etoh T et al. Transplacental leakage of HBeAg-positive maternal blood as the most likely route in causing intrauterine infection with hepatitis B virus. J Pediatr 1987; 111 (6 Pt 1): 877–881.

    Article  CAS  Google Scholar 

  6. Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A . Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci USA 1990; 87: 6599–6603.

    Article  CAS  Google Scholar 

  7. Yue Y, Meng J, Zhang S . Mechanism of peripheral blood mononuclear cell invasion by HBV on artificial immunization in newborns. Chin Med J (Engl) 2002; 115: 1380–1382.

    Google Scholar 

  8. Milich D, Liang TJ . Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology 2003; 38: 1075–1086.

    Article  CAS  Google Scholar 

  9. Ranger-Rogez S, Alain S, Denis F . Hepatitis viruses: mother to child transmission. Pathol Biol (Paris) 2002; 50: 568–575. French.

    Article  CAS  Google Scholar 

  10. Wang F, Zhang J, Yang H, Li X, Wen S, Guo Y et al. Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies. J Med Virol 2003; 71: 360–366.

    Article  CAS  Google Scholar 

  11. Kane M . Global programme for control of hepatitis B infection. Vaccine 1995; 13 (Suppl. 1): S47–S49.

    Article  Google Scholar 

  12. Lazizi Y . Trasplacental passage of hepatitis B virus DNA from hepatitis B e antigen-negative mothers and delayed immune response in newborns. J Infec Dis 1994; 169: 704–706.

    Article  Google Scholar 

  13. Paraskevis D, Haida C, Tassopoulos N, Raptopoulou M, Tsantoulas D, Papachristou H et al. Development and assessment of a novel real-time PCR assay for quantitation of HBV DNA. J Virol Methods 2002; 103: 201–212.

    Article  CAS  Google Scholar 

  14. Paraskevis D, Katsoulidou C, Moschidis Z, Hatzitheodorou E, Varaklioti A, Hatzakis A . Development of a flexible and sensitive in-house real-time PCR assay for the quantification of HBV DNA. Proceeding of XVIIth Regional Congress. Madrid: International Society of Blood Transfusion, 2007.

    Google Scholar 

  15. Jafarzadeh A, Shokri F . The antibody response to HBs antigen is regulated by coordinated Th1 and Th2 cytokine production in healthy neonates. Clin Exp Immunol 2003; 131: 451–456.

    Article  CAS  Google Scholar 

  16. Ota MO, Vekemans J, Schlegel-Haueter SE, Fielding K, Whittle H, Lambert PH et al. Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults. Vaccine 2004; 22: 511–519.

    Article  CAS  Google Scholar 

  17. Brunetto MR, Giarin MM, Oliveri F, Chiaberge E, Baldi M, Alfarano A et al. Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc Natl Acad Sci USA 1991; 88: 4186–4190.

    Article  CAS  Google Scholar 

  18. Pontisso P, Vidalino L, Quarta S, Gatta A . Biological and clinical implications of HBV infection in peripheral blood mononuclear cells. Autoimmun Rev 2008; 8: 13–17.

    Article  Google Scholar 

  19. Jafarzadeh A, Kardar G, Khoshnoodi J, Shokri F . Downregulation of IL-12 production in healthy non-responder neonates to recombinant hepatitis B vaccine. Iran Biomed J 2004; 8: 41–45.

    CAS  Google Scholar 

  20. Keating GM, Noble S . Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B. Drugs 2003; 63: 1021–1051.

    Article  CAS  Google Scholar 

  21. Chang MH . Hepatitis B virus infection. Semin Fetal Neonatal Med 2007; 12: 160–167.

    Article  Google Scholar 

  22. Borkowsky W, Krasinski K, Moore T, Papaevangelou V . Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children. AIDS Res Hum Retroviruses 1990; 6: 673–678.

    Article  CAS  Google Scholar 

  23. Rich KC, Siegel JN, Jennings C, Rydman RJ, Landay AL . Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers. Clin Diagn Lab Immunol 1997; 4: 358–361.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Pride MW, Thakur A, Thanavala Y . Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains. J Exp Med 1993; 177: 127–134.

    Article  CAS  Google Scholar 

  25. Koumbi L, Papadopoulos N, Anastassiadou V, Machaira M, Kafetzis D, Papaevangelou V . Dendritic cells in uninfected infants born to hepatitis B virus positive mothers. Clin Vaccine Immunol 2010; in press.

  26. Li RB, Chen HS, Xie Y, Fei R, Cong X, Jiang D et al. Dendritic cells from chronic hepatitis B patients can induce HBV antigen-specific T cell responses. World J Gastroenterol 2004; 10: 1578–1582.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Glaxo SmithKline Biologicals, Belgium, and Rhein Biotech Dynavax, Germany, for kindly providing the purified preparations of HBsAg and HBc antigens, respectively. We are particularly grateful to the subjects and the mothers who allowed their babies to be enrolled in the study. We also thank Dr Apostolos Bossios and Dr Christina Piperi for their consultation assistance in developing the experimental techniques used in this study. The study was cofunded by the European Social Fund and National Resources—(EPEAEK II) PYTHAGORAS and was also supported by a European Society of Pediatric Diseases Small Grant and a fellowship from the European Society of Clinical Microbiology and Infectious Diseases.

Author information

Authors and Affiliations

  1. Second Department of Pediatrics, Allergy Research Center, University of Athens, Athens, Greece

    Lemonica Koumbi & Nikolaos G Papadopoulos

  2. Singapore Institute for Clinical Sciences, A*STAR, Singapore

    Antonio Bertoletti & Winnie Goh

  3. Alexandra Maternal Hospital, University of Athens, Athens, Greece

    Vassiliki Anastasiadou

  4. Second Department of Pediatrics, University of Athens, P&A Kyriakou Children's Hospital, Athens, Greece

    Maria Machaira, Dimitris A Kafetzis & Vassiliki Papaevangelou

Authors
  1. Lemonica Koumbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Bertoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vassiliki Anastasiadou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Machaira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Winnie Goh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nikolaos G Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dimitris A Kafetzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vassiliki Papaevangelou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lemonica Koumbi.

Additional information

Note: Supplementary information is available on the Cellular & Molecular Immunology website.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koumbi, L., Bertoletti, A., Anastasiadou, V. et al. Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg− mothers. Cell Mol Immunol 7, 454–458 (2010). https://doi.org/10.1038/cmi.2010.34

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2010.34

Keywords

This article is cited by

Search

Advanced search

Quick links