Comprehensive tracking of Hepatitis B vaccines including recombinant formulations, universal infant vaccination, birth dose strategy, and chronic infection prevention. HBV vaccine (first recombinant vaccine licensed 1986) prevents chronic infection, cirrhosis, and liver cancer - one of the first cancer-preventing vaccines.
Global Burden - A Major Public Health Crisis: WHO estimates 296 million people living with chronic HBV infection (2019), 820,000 deaths annually from HBV-related cirrhosis and hepatocellular carcinoma (HCC). New infections: 1.5 million annually despite vaccine availability. Geographic distribution: Highest burden in WHO Western Pacific Region (116 million chronic infections - includes China) and Africa (82 million), intermediate burden in Southeast Asia, Eastern Mediterranean. HBV endemic countries (≥8% population chronically infected pre-vaccination): Sub-Saharan Africa, East Asia, Pacific Islands, parts of Middle East, Amazon Basin, parts of Eastern Europe. United States: ~850,000-2.2 million chronic HBV infections, predominantly foreign-born individuals from endemic regions, Alaska Native populations, certain immigrant communities. Annual U.S. deaths: 1,800-3,000 from HBV-related cirrhosis/liver cancer.
Age-Dependent Risk of Chronic Infection - The Cruel Paradox: HBV has inverse relationship between age at infection and chronicity risk. Perinatal infection (birth to 12 months): 90% become chronically infected (infants lack mature immune system, develop immune tolerance to HBV), vertical transmission from HBsAg-positive mothers major driver of chronic HBV burden globally, most infected infants asymptomatic initially but 25% develop cirrhosis or HCC by age 40-50. Early childhood (1-5 years): 25-50% become chronic, common in endemic areas with horizontal transmission (household contacts, contaminated instruments). Older children/adolescents (>5 years): 5-10% chronicity. Adults: <5% chronicity, most clear infection developing lifelong immunity, symptomatic acute hepatitis more common in adults than children. Chronic HBV carries 15-25% lifetime risk of death from cirrhosis or HCC if untreated. This age-dependent pattern makes infant/childhood vaccination critical (prevents acquisition during high-risk age).
Clinical Manifestations: Acute HBV: Incubation 60-150 days (average 90 days), most infections asymptomatic or mild (70-80% in children, 50-70% in adults never know they were infected), symptomatic acute hepatitis (fatigue, nausea, jaundice, right upper quadrant pain, dark urine) lasts 2-12 weeks, fulminant hepatic failure rare (0.1-0.5%) but fatal without transplant, 95%+ adults clear virus completely developing anti-HBs antibodies (lifelong immunity). Chronic HBV: Defined as HBsAg persistence >6 months, asymptomatic for years-decades ("healthy carrier" state - normal liver enzymes, minimal inflammation), immune-active phase develops eventually (elevated ALT, active viral replication, progressive liver damage), 20-30% develop cirrhosis over 20-30 years, cirrhotic patients have 3-6% annual risk of HCC, 15-25% lifetime mortality from liver disease if untreated. Treatment exists (entecavir, tenofovir - suppress viral replication, prevent progression) but cannot cure (eliminate covalently closed circular DNA in hepatocytes), requires lifelong therapy, highlighting importance of prevention through vaccination.
Viral Biology & Transmission: Hepatitis B virus (HBV) is hepadnavirus, partially double-stranded DNA virus, enveloped. Remarkably stable (survives 7+ days on environmental surfaces at room temperature, resistant to freezing/drying, requires high-level disinfection). Transmission routes: Perinatal/vertical (mother to baby during delivery - major route in endemic areas, 90% transmission risk if mother HBeAg-positive without intervention), percutaneous (injection drug use sharing needles, unsafe medical injections, tattooing/piercing with contaminated equipment, needlestick injuries in healthcare), sexual contact (all forms - heterosexual and MSM, HBV 50-100x more infectious than HIV), household (horizontal transmission via shared razors/toothbrushes, bites, open wounds, saliva contact - important in endemic areas). Blood-borne transmission historically important (transfusions pre-screening era 1970s-1980s, now rare with universal blood donor screening). Viral proteins: HBsAg (surface antigen - envelope protein, detected in blood indicating infection, target of vaccine and anti-HBs antibodies conferring immunity), HBcAg (core antigen), HBeAg (secreted protein correlating with high viral replication and infectivity), HBV DNA (viral load marker).
Liver Health Resources →Technology Breakthrough: First recombinant DNA vaccine licensed (1986), pioneering achievement in vaccinology. Recombinant HBsAg produced in Saccharomyces cerevisiae (baker's yeast) - HBsAg gene inserted into yeast plasmid, yeast cells express HBsAg protein, purified HBsAg assembled into 22 nm virus-like particles (VLPs) mimicking HBV surface antigen, adsorbed to aluminum hydroxide adjuvant. Replaced plasma-derived vaccine (made from HBsAg purified from chronically infected blood donors, concerns about transmission of unknown bloodborne pathogens drove shift to recombinant technology despite excellent safety record of plasma vaccine).
Formulations: Pediatric/Adolescent (5 μg HBsAg/0.5 mL) for birth-19 years, Adult (10 μg/1.0 mL) for ≥20 years, Dialysis (40 μg/1.0 mL) for hemodialysis patients and immunocompromised (higher dose overcomes reduced immune response). Three-dose schedule: 0, 1, 6 months (dose 1 at enrollment, dose 2 at 1 month, dose 3 at 6 months), alternative accelerated schedule for post-exposure: 0, 1, 4 months. Intramuscular deltoid (adults) or anterolateral thigh (infants).
Efficacy: After 3-dose series: 95-99% of healthy infants/children/young adults develop protective anti-HBs antibodies (≥10 mIU/mL protective threshold), 90-95% of healthy adults 20-40 years, 75-90% adults >40 years (declining with age due to immunosenescence), 40-70% dialysis patients/immunocompromised (reduced response necessitating higher dose, checking antibody titers). Duration of protection: Antibody titers decline over years, but immunological memory persists, protective efficacy >90% maintained 20-30 years post-vaccination in immunocompetent individuals, breakthrough infections extremely rare and usually non-chronic, lifelong protection expected in most vaccinated as children.
Safety: Excellent safety profile, one of the safest vaccines. Common reactions: Injection site soreness (10-25%), low-grade fever (1-6%), fatigue, headache. Serious adverse events not causally linked (extensive studies disproved associations with multiple sclerosis, SIDS, autoimmune diseases). Safe in: Pregnancy (limited data but recombinant protein vaccine, theoretical low risk, given to pregnant women at high HBV exposure risk), HIV-positive (reduced response but still worth vaccinating, use higher dose or additional doses, check titers), chronic liver disease.
Technology: Similar recombinant HBsAg produced in yeast, different manufacturing process and formulation than Recombivax. Aluminum hydroxide adjuvant. Formulations: Pediatric (10 μg HBsAg/0.5 mL) for birth-19 years (note: different from Recombivax 5 μg pediatric dose but both effective), Adult (20 μg/1.0 mL) for ≥20 years, Dialysis (40 μg/1.0 mL, given as 4-dose series: 0, 1, 2, 6 months for hemodialysis patients). Three-dose schedule: 0, 1, 6 months. Also available in 2-dose adolescent schedule (10-15 years): 0, 6 months using adult dose formulation (20 μg x 2 doses = 40 μg total, comparable to 3-dose pediatric series 10 μg x 3 = 30 μg, approved based on non-inferior immunogenicity).
Efficacy & Safety: Equivalent to Recombivax (95-99% seroprotection after 3 doses in healthy individuals, 20-30 year duration). Interchangeable with Recombivax (can complete series with either vaccine regardless of which used initially, though same brand preferred). Widely used internationally, WHO-prequalified.
Combination Vaccines: Engerix-B is component of: Twinrix (HAV + HBV for adults), Pediarix (DTaP-HepB-IPV for infants), hexavalent vaccines in Europe (DTaP-HepB-IPV-Hib like Infanrix hexa).
Innovation: Licensed 2017, first new HBV vaccine in 25+ years. Contains recombinant HBsAg (20 μg) adjuvanted with CpG 1018 (novel toll-like receptor 9 agonist synthetic oligonucleotide adjuvant). CpG adjuvant enhances immune response enabling two-dose schedule. For adults ≥18 years only.
Schedule: Two-dose series: 0, 1 month (dose 1 at enrollment, dose 2 at 1 month), much faster completion than traditional 0, 1, 6 month three-dose series. Particularly advantageous for: Adults unlikely to complete 3-dose series (homeless, substance use disorder, incarcerated - populations at high HBV risk with poor healthcare engagement), healthcare workers needing rapid protection, travelers departing soon.
Efficacy: Non-inferior to Engerix-B three-dose series. Pivotal trials: 95% seroprotection after 2-dose Heplisav-B vs. 81% after 3-dose Engerix-B at 6-month timepoint (superior seroconversion particularly in adults >40 years, diabetics - populations with poor response to traditional vaccines), faster protection (protective antibodies by month 2 vs. month 7 for traditional vaccines). FDA approved based on demonstrated non-inferiority and superior seroconversion rates.
Safety: Generally well-tolerated. Slightly higher injection site reactions than aluminum-adjuvanted vaccines (pain, redness 25-35% vs. 15-25%, expected with CpG adjuvant enhancing local inflammatory response). Post-marketing surveillance: Potential signal for myocardial infarction in first 1-2 days post-vaccination observed (FDA review concluded causal relationship not established, MI cases had underlying cardiovascular risk factors, benefits outweigh theoretical risk, no change to recommendations). Contraindication: Known severe allergy to yeast or previous severe reaction to HBV vaccine.
Usage: ACIP added to recommended vaccines 2018, gaining market share particularly in populations benefiting from 2-dose schedule (15-25% U.S. adult HBV vaccine market by 2023). More expensive than traditional vaccines but improved completion rates may offset cost.
Rationale for Birth Dose: Perinatal transmission accounts for 30-50% of chronic HBV burden in endemic areas. Without intervention, infants born to HBsAg-positive mothers have 70-90% transmission risk (highest if mother also HBeAg-positive indicating high viral load). Birth dose within 24 hours: Provides immediate protection during highest-risk period (HBV exposure during delivery from maternal blood), induces immune response before potential HBV infection establishes chronicity, combined with HBIG (hepatitis B immune globulin) in infants of HBsAg-positive mothers provides 85-95% protection against perinatal transmission (vs. 10-30% with HBIG alone, 30-40% with vaccine alone). WHO recommends: Universal birth dose within 24 hours of birth regardless of maternal HBsAg status (simplifies programs, catches unscreened mothers, protects against horizontal transmission in endemic areas). Complete series: Birth dose followed by 2-3 additional doses at 1-2, 4, 6 months (monovalent HBV vaccine or combination vaccines like Pediarix after birth dose). Schedule: Birth dose must be monovalent HBV (combination vaccines not licensed for birth dose due to other components' age restrictions).
U.S. Implementation & Impact: Universal infant HBV vaccination recommended 1991, universal birth dose (<24 hours) recommended 2005 for all medically stable infants ≥2000 grams. Current U.S. schedule: Birth dose (day 0-1), dose 2 (1-2 months), dose 3 (6-18 months typically given at 6 months), alternatively can use combination vaccine (Pediarix) for doses 2 and 3 at 2, 4, 6 months if infant received birth dose monovalent vaccine. Catch-up: Unvaccinated children/adolescents receive 3-dose series at any age. Maternal HBsAg-positive infants: Birth dose within 12 hours PLUS HBIG 0.5 mL IM (separate site) within 12 hours, complete 3-dose series, postvaccination serologic testing at 9-12 months (check anti-HBs to confirm protection, check HBsAg to detect breakthrough infection). Impact: Perinatal HBV transmission declined 95% in U.S. (pre-vaccine 1980s: 30,000 annual perinatal infections, 2010s: <1,000), acute HBV cases in children <19 years nearly eliminated (2018: 42 cases nationally vs. 3,200 cases in 1990 despite population growth), chronic HBV infections in U.S.-born children aged 6-19 declined from 1.1% (1988-1994) to 0.01% (2011-2018) = 99% reduction.
Global Implementation: WHO introduced universal infant HBV vaccination into Expanded Program on Immunization (EPI) 1992. Global HepB3 coverage (3rd dose infant series): 85% of infants (2021) up from <1% (1990), birth dose (<24 hours) coverage: 46% globally (2021) but varies dramatically (Western Pacific 84%, Africa 18%), remaining gap preventing millions of perinatal infections. 187 countries include HBV in routine infant vaccination (2021). Impact in endemic countries: Taiwan pioneering program (1984): chronic HBV prevalence in children dropped from 10-15% to <1%, HCC incidence in children decreased 70%, similar success in Thailand, China (introduced universal vaccination 2002, chronic HBV in children <5 years declined from 10% to <1%), Africa implementing with Gavi support since 2000s seeing early impacts.
CDC Hepatitis B: Vaccination schedules, testing recommendations, screening guidelines. CDC Hep B
WHO - Hepatitis B: Global strategy for hepatitis elimination, vaccination policies, treatment guidelines. WHO Hep B
CDC Pink Book - Hepatitis B Chapter: Comprehensive epidemiology, clinical features, vaccination guidance. Pink Book
ACIP Hepatitis B Vaccine Recommendations: Detailed schedules, catch-up vaccination, post-exposure prophylaxis. ACIP Recs
Perinatal Hepatitis B Prevention: Maternal screening, infant vaccination, HBIG administration. Perinatal Prevention
AASLD Guidelines: Treatment indications, monitoring chronic HBV, management of complications. AASLD Guidelines