Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100？IU/kg HBIGIV 2–5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia. 1. Introduction Chronic hepatitis B is a serious viral disease, associated with a high risk for developing liver cirrhosis and hepatocellular carcinoma [1–3]. Worldwide, two billion people have been infected with the virus and about 600,000 people die every year due to the consequences of hepatitis B [4]. HBV is endemic in China and other parts of Asia where 8–10% of the adult population is chronically infected, often since birth. Because 90% of infants infected at birth develop chronic HBV infection and 25% of those die prematurely from cirrhosis or liver cancer [5, 6], failure to prevent infection following perinatal exposure to HBV carries a heavy burden to the individual, family, and society at large. Passive-active postexposure prophylaxis (PEP) with HBIG and hepatitis B vaccine is 85–95% effective in preventing vertical transmission of HBV compared to 70–95% prevention rate for the vaccine alone [6, 7]. Despite PEP, 3–13% of infants born to infected mothers acquire HBV [8]. The risk is particularly high for children born to mothers with a high viral load [9, 10]. Although pregnancy, especially the peripartum period, has been associated with an increase in hepatitis B viral load [11], maternal use of antiviral drugs, such as nucleoside analogs, as an adjunct to PEP of the newborn has not shown
References
[1]
C. M. Weinbaum, I. Williams, E. E. Mast et al., “Recommendations for identification and public health management of persons with chronic hepatitis B virus infection,” MMWR Recommendations and Reports, vol. 57, article RR08, pp. 1–20, 2008.
[2]
M. F. Sorrell, E. A. Belongia, J. Costa et al., “National Institutes of Health Consensus Development Conference Statement: management of hepatitis B,” Annals of Internal Medicine, vol. 150, no. 2, pp. 104–110, 2009.
[3]
C. W. Shepard, E. P. Simard, L. Finelli, A. E. Fiore, and B. P. Bell, “Hepatitis B virus infection: epidemiology and vaccination,” Epidemiologic Reviews, vol. 28, no. 1, pp. 112–125, 2006.
[4]
WHO, “Hepatitis B vaccines,” The Weekly Epidemiological Record, vol. 84, no. 40, pp. 405–419, 2009.
[5]
C. E. Stevens, R. P. Beasley, J. Tsui, and W. C. Lee, “Vertical transmission of hepatitis B antigen in Taiwan,” The New England Journal of Medicine, vol. 292, no. 15, pp. 771–774, 1975.
[6]
E. E. Mast, H. S. Margolis, A. E. Fiore et al., “A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents,” MMWR Recommendations and Reports, vol. 54, article RR16, pp. 1–31, 2005.
[7]
E. E. Mast, C. M. Weinbaum, A. E. Fiore et al., “A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part II: immunization of adults,” MMWR Recommendations and Reports, vol. 55, article RR16, pp. 1–25, 2006.
[8]
G. Borgia, M. A. Carleo, G. B. Gaeta, and I. Gentile, “Hepatitis B in pregnancy,” World Journal of Gastroenterology, vol. 18, no. 34, pp. 4677–4683, 2012.
[9]
H. M. H. Ip, V. C. W. Wong, P. N. Lelie, M. C. Kuhns, and H. W. Reesink, “Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA,” The Lancet, vol. 1, no. 8635, pp. 406–410, 1989.
[10]
Z. Shi, X. Li, L. Ma, and Y. Yang, “Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission—a meta-analysis,” International Journal of Infectious Diseases, vol. 14, no. 7, pp. e622–e634, 2010.
[11]
A. S？derstr？m, G. Norkrans, and M. Lindh, “Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission,” Scandinavian Journal of Infectious Diseases, vol. 35, no. 11-12, pp. 814–819, 2003.
[12]
N. Leung, “Chronic hepatitis B in Asian women of childbearing age,” Hepatology International, vol. 3, no. 1, pp. 24–31, 2009.
[13]
H. Elvidge, “Production of dated pregnant guinea pigs without post-partum matings,” Journal of the Institute of Animal Technicians, vol. 23, no. 3, pp. 111–117, 1972.
[14]
E. B. Struble, L. Ma, L. Zhong, A. Lesher, J. Beren, and P. Zhang, “Human antibodies can cross guinea pig placenta and bind its neonatal Fc receptor: implications for studying immune prophylaxis and therapy during pregnancy,” Clinical and Developmental Immunology, vol. 2012, Article ID 538701, 9 pages, 2012.
[15]
J. W. Ward, “Time for renewed commitment to viral hepatitis prevention,” American Journal of Public Health, vol. 98, no. 5, pp. 779–781, 2008.
[16]
D. FitzSimons, G. Hendrickx, A. Vorsters, and D. P. Van, “Hepatitis B vaccination: a completed schedule enough to control HBV lifelong? Milan, Italy, 17-18 November 2011,” Vaccine, vol. 31, no. 4, pp. 584–590, 2013.
[17]
A. Zidan, H. Scheuerlein, S. Schule, U. Settmacher, and F. Rauchfuss, “Epidemiological pattern of hepatitis B and hepatitis C as etiological agents for hepatocellular carcinoma in Iran and worldwide,” Hepatitis Monthly, vol. 12, no. 10, Article ID e6894, 2012.
[18]
N. Linder, T. H. Vishne, E. Levin et al., “Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols,” Infection, vol. 30, no. 3, pp. 136–139, 2002.
[19]
J. P. Hieber, D. Dalton, J. Shorey, and B. Combes, “Hepatitis and pregnancy,” Journal of Pediatrics, vol. 91, no. 4, pp. 545–549, 1977.
[20]
R. W. Pitcher-Wilmott, P. Hindocha, and C. B. S. Wood, “The placental transfer of IgG subclasses in human pregnancy,” Clinical and Experimental Immunology, vol. 41, no. 2, pp. 303–308, 1980.
[21]
A. Malek, R. Sager, and H. Schneider, “Maternal-fetal transport of immunoglobulin G and its subclasses during the third trimester of human pregnancy,” American Journal of Reproductive Immunology, vol. 32, no. 1, pp. 8–14, 1994.
[22]
N. E. Simister, “Placental transport of immunoglobulin G,” Vaccine, vol. 21, no. 24, pp. 3365–3369, 2003.
[23]
W. A. Marasco and J. Sui, “The growth and potential of human antiviral monoclonal antibody therapeutics,” Nature Biotechnology, vol. 25, no. 12, pp. 1421–1434, 2007.
[24]
J. Schupbach, H. Gunthard, M. S. C. Fung et al., “Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in patients with HIV-1 disease,” Biotherapy, vol. 6, no. 3, pp. 205–215, 1993.
[25]
C. Onyango-Makumbi, S. B. Omer, M. Mubiru et al., “Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY),” Journal of Acquired Immune Deficiency Syndromes, vol. 58, no. 4, pp. 399–407, 2011.
