ReviewSeroprotection after recombinant hepatitis B vaccination among newborn infants: A review☆
Highlights
► 98% of term infants attain seroprotection after hepatitis B vaccination. ► Seroprotection is reduced among infants with birth weights <2000 g. ► Seroprotection does not vary with maternal HBsAg status, HBIG, or schedule.
Introduction
Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver failure and cancer worldwide [1]. Chronic HBV infection occurs in approximately 90% of infected infants, in contrast to fewer than 5% of persons infected at 5 years of life or older [2]. Historically, perinatal or childhood transmission accounted for 30–40% of chronic HBV infections in the United States [2]. Pregnant women with acute or chronic HBV infection are an important source of hepatitis B for their infants. Although a small proportion of infants are infected in utero, exposure to blood or body fluids during birth is a major route of transmission for HBV infection among infants [3]. Early life transmission also occurs through contact with infected siblings or care providers who may be unaware of their infection [4], [5], [6], [7], [8]. Although chronic HBV infections acquired in early life are largely asymptomatic, up to a quarter of these infections result in premature death from complications including cirrhosis, liver failure, or liver cancer [9]. Persons with chronic HBV infection are the main reservoir for transmission [2], [10].
The first hepatitis B vaccine consisted of plasma-derived hepatitis B surface antigen (HBsAg). In 1982, the Advisory Committee on Immunization Practices (ACIP) recommended administration of hepatitis B immune globulin (HBIG) for infants born to HBsAg-positive mothers, followed by hepatitis B vaccination beginning at three months of age [11]. Clinical trials were structured so that infants received the initial dose of vaccine at birth, followed by completion of a 3 or 4 dose vaccine series [12], [13], [14]. Among high-risk infants, the efficacy of plasma-derived vaccine plus HBIG ranged from 66% to 100% [15].
Recombinant hepatitis B vaccines containing yeast-derived HBsAg replaced the plasma-derived vaccines in the United States by the late 1980s. Hepatitis B vaccination has been universally recommended for infants in the United States since 1991. The recommendation specified administration of the first dose by 2 months of age, with a preference for administration before birthing facility discharge [16]. In 2005, an update to the recommendation specified the first dose should be a “birth dose,” i.e., administered to infants with birth weights ≥2000 g before birthing facility discharge as a safety net for early life prevention of HBV infection, or to all infants born to HBsAg-positive mothers within 12 h of birth [2]. As such, hepatitis B vaccination starting at birth is unique from other routine infant immunizations recommended in most countries that commence at 6 weeks to 2 months of life or later [17]. Prevention of perinatal or early life HBV infection underlies the recommendation for hepatitis B vaccination starting at birth.
Primary infant hepatitis B vaccination in the United States consists of three doses of 5 or 10 μg of monovalent recombinant vaccine administered intramuscularly on a 0, 1–2, and 6–18 months schedule. Other schedules are available in the United States (Table 1). Either of two monovalent vaccines (Recombivax HB® [Merck & Co, Inc., Whitehouse Station, NJ, US] and Engerix-B® [GlaxoSmithKline Biologicals, Rixensart, Belgium]) may be used. Combination vaccines may be used for doses administered at ages 6 weeks or older provided other indications are heeded [2].
In this review, we summarize the seroprotection proportions and immunogenicity of recombinant hepatitis B vaccine found in trials that administered recombinant hepatitis B vaccine starting within the first 30 days of life. We highlight some of the issues and gaps in knowledge related to the widespread use of hepatitis B vaccine for prevention of perinatal and early life acquisition of HBV infection.
Section snippets
Search strategy
An electronic search of MEDLINE (via PubMed) and EMBASE (via Ovid) using combinations of search terms (hepatitis b vaccin*, hbv vaccin*, hepatitis b immuni*, hbv immuni*, immunogeni*, immune response, antibody, neona*, infan*, birth) was performed, including errata. Limits included publication date from January 1, 1987 (1988 for EMBASE) through December 16, 2011, English language, humans, and age birth through one month (through one year for EMBASE), without restriction for country where the
Results
The electronic search yielded 833 studies (available upon request). Based on review of titles and/or abstracts, full texts were retrieved and reviewed for 93 studies (11.2%). Of these, 34 (36.6%) met study criteria. An additional 13 studies were identified from manual review of personal files and reference lists. Four studies were excluded for reporting on duplicate subjects. A total of 43 studies reporting on 9368 infant subjects in 100 arms were included in this review (Table 2). Twenty were
Discussion
This review provides a summary of 43 studies of recombinant hepatitis B vaccine conducted among infants since 1987. The studies included more than 9000 infants in 20 countries, with 15 vaccines from 13 manufacturers. Most trials were designed to examine the response to vaccination starting at birth, under a variety of conditions. Overall, a median 98% (range 52%, 100%) of infants achieved seroprotective concentrations of anti-HBs after 3 or 4 doses of hepatitis B vaccine, including infants born
Conclusions
High levels of seroprotection are achieved after recombinant hepatitis B vaccination starting at birth, regardless of maternal HBsAg status. As such, hepatitis B vaccination at birth prevents perinatal transmission of HBV and HBV-related morbidity and mortality. Administration of HBIG with the first dose of hepatitis B vaccine did not affect the response to vaccination. Seroprotection was lower among infants with birth weights <2000 g but improved when vaccination was initiated at ≥30 days of
Acknowledgements
None. Conflicts of interest: No authors reported any conflicts of interest.
References (76)
Perinatal transmission of hepatitis B virus in high-incidence countries
J Virol Methods
(1987)- et al.
Transmission of hepatitis B virus infection in Gambian families revealed by phylogenetic analysis
J Hepatol
(2001) - et al.
Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study
Lancet
(1984) - et al.
Protective efficacy of hepatitis B vaccine without HBIG in infants of HBeAg-positive carrier mothers in Thailand
Vaccine
(2002) - et al.
Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus in infants born to HBsAg positive mothers in comparison with vaccine alone
Hepatol Res
(2006) - et al.
Immunogenicity and safety in newborns of a new recombinant hepatitis B vaccine containing the S and pre-S2 antigens
Vaccine
(1991) - et al.
Immunogenicity of hepatitis B vaccine in preterm and full term infants vaccinated within the first week of life
Vaccine
(2002) - et al.
High seroprotection rate induced by low doses of a recombinant hepatitis B vaccine in healthy Iranian neonates
Vaccine
(2001) - et al.
A reduced dose approach to hepatitis B vaccination for low-risk newborns and preschool children
Vaccine
(1995) - et al.
Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants
J Pediatr
(1997)
Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine
Lancet
Lifelong protection against hepatitis B: the role of vaccine immunogenicity in immune memory
Vaccine
Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults
Vaccine
Safety and immunogenicity of hepatitis B vaccine administered into ventrogluteal vs. anterolateral thigh sites in infants: a randomised controlled trial
Int J Nurs Stud
Response of preterm infants to hepatitis B vaccine
J Pediatr
Seroconversion of hepatitis B vaccine in infants related to the mother's serostatus in a community of Sao Jose dos Campos, state of Sao Paulo, Brazil
Clinics (Sao Paulo, Brazil)
Antibody response to hepatitis B vaccine in infants of HIV-positive mothers
Int J Infect Dis
Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C
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 Recomm Rep
Natural history of hepatitis B virus infection: pediatric perspective
J Gastroenterol
Familial clustering of hepatitis B infection
N Engl J Med
Hepatitis B virus infection in Chinese families in Hong Kong
Am J Epidemiol
Epidemiology of hepatitis B infection in Liberian infants
Infect Immun
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 Recomm Rep
Recommendation of the Immunization Practices Advisory Committee (ACIP) inactivated hepatitis B virus vaccine
Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial
Pediatrics
Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area
J Med Virol
Review: protective efficacy of hepatitis B vaccines in neonates
J Med Virol
Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP)
MMWR Recomm Rep
What level of hepatitis B antibody is protective?
J Infect Dis
B immunization: vaccine types, efficacy, and indications for immunization
Curr Clin Top Infect Dis
Sensitivity of the test for antibody to hepatitis B surface antigen – United States
MMWR Morb Mortal Wkly Rep
Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers
JAMA
The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen–positive-hepatitis B surface antigen carrier mothers
Pediatr Infect Dis J
An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China
Int J Epidemiol
Immunogenicity and efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur in high risk neonates, school children and healthy adults
Asian Pac J Allergy Immunol
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The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.