Hepatitis A Vaccines
Introduction to Hepatitis A Vaccines
Hepatitis A vaccines are designed to prevent infection caused by the hepatitis A virus (HAV), a picornavirus that primarily affects the liver.
- Pathogen: Hepatitis A virus, a non-enveloped, single-stranded RNA virus
- Transmission: Fecal-oral route, contaminated food or water, close person-to-person contact
- Disease burden: Estimated 1.4 million cases annually worldwide, with higher prevalence in low- and middle-income countries
- Clinical presentation: Ranges from asymptomatic infection to fulminant hepatitis; severity increases with age
Hepatitis A vaccines, first licensed in 1992, have become an essential tool in preventing HAV infection and its complications, particularly in high-risk populations and as part of routine childhood immunization in many countries.
Vaccine Types
There are several inactivated hepatitis A vaccines available globally. The main types used in many countries include:
1. Single-antigen Hepatitis A Vaccines
- Havrix: Manufactured by GlaxoSmithKline
- Vaqta: Manufactured by Merck
2. Combination Vaccines
- Twinrix: Combined hepatitis A and hepatitis B vaccine (GlaxoSmithKline)
Vaccine Composition
All hepatitis A vaccines contain inactivated (killed) whole hepatitis A virus:
- Grown in cell culture
- Purified by ultrafiltration and chromatography
- Inactivated with formalin
- Adsorbed to an aluminum hydroxide adjuvant
Other Components
- 2-phenoxyethanol (preservative)
- Traces of neomycin (Havrix)
- Bovine albumin (Vaqta)
The vaccines do not contain live virus and cannot cause hepatitis A infection.
Administration
Hepatitis A vaccines are administered intramuscularly, typically into the deltoid muscle for adults and older children, or the anterolateral thigh for infants.
Vaccination Schedule
Single-antigen Vaccines (Havrix, Vaqta)
- Children: Two doses; second dose 6-18 months after the first
- Adults: Two doses; second dose 6-12 months after the first
Combination Vaccine (Twinrix)
- Standard schedule: Three doses at 0, 1, and 6 months
- Accelerated schedule: Four doses at 0, 7, 21-30 days, and 12 months
Age Recommendations
- Havrix: Approved for use in persons 12 months of age and older
- Vaqta: Approved for use in persons 12 months of age and older
- Twinrix: Approved for use in persons 18 years of age and older
Catch-up Vaccination
For individuals who have not completed the series, the second dose should be administered as soon as possible. There is no need to restart the series if the interval between doses is longer than recommended.
Co-administration
Hepatitis A vaccines can be administered concurrently with other vaccines, using separate syringes and injection sites.
Efficacy
Hepatitis A vaccines have demonstrated high efficacy in preventing HAV infection:
Seroconversion Rates
- 95-100% of vaccinees develop protective antibodies within 4 weeks after a single dose
- Nearly 100% seroconversion after two doses
Clinical Efficacy
- 94-100% protection against clinical hepatitis A in clinical trials
- Efficacy demonstrated in outbreak control settings
Duration of Protection
- Anti-HAV antibodies persist for at least 20-25 years in adults
- Mathematical models predict lifelong protection after a complete series
- No booster doses currently recommended for immunocompetent individuals
Factors Affecting Efficacy
- Age: Lower immunogenicity in older adults, but still highly effective
- Immunocompromised status: May have reduced immune response
- Timing of administration: Postexposure prophylaxis most effective if given within 2 weeks of exposure
Cross-protection
Vaccines based on one HAV strain provide protection against all known strains due to the existence of a single serotype.
Safety Profile
Hepatitis A vaccines have an excellent safety record, with millions of doses administered globally.
Common Adverse Events
- Local reactions:
- Soreness at injection site (50-60% of adults)
- Redness or swelling (20-30% of adults)
- Systemic reactions:
- Headache (10-15% of adults)
- Fatigue (5-10% of adults)
- Low-grade fever (1-5% of adults)
Serious Adverse Events
- Anaphylaxis: Extremely rare (estimated <1 per million doses)
- No increased risk of Guillain-Barré syndrome or other autoimmune disorders
Safety in Special Populations
- Pregnancy: No evidence of adverse effects on the fetus
- Immunocompromised individuals: Generally safe, but may have reduced immunogenicity
- Children: Similar safety profile to adults, with lower rates of systemic side effects
Long-term Safety
No long-term adverse effects have been associated with hepatitis A vaccination.
Contraindications
Absolute Contraindications
- Severe allergic reaction (e.g., anaphylaxis) after a previous dose of hepatitis A vaccine
- Severe allergic reaction to any vaccine component
Precautions
- Moderate or severe acute illness: Defer vaccination until condition improves
- Pregnancy: Theoretical risk to the fetus; use only if clearly needed
- Bleeding disorders: Use with caution due to risk of hematoma at injection site
Not Contraindications
- Mild acute illness with or without fever
- Current or previous HAV infection
- Pregnancy (for postexposure prophylaxis or high-risk situations)
- Breastfeeding
- Immunosuppression (vaccine may be less effective but is not contraindicated)
- Autoimmune disease
Considerations for Combination Vaccines
For Twinrix (combination hepatitis A and B vaccine), contraindications and precautions for both hepatitis A and hepatitis B vaccines should be considered.
Special Populations
Travelers
- Recommended for travelers to countries with intermediate or high HAV endemicity
- Ideally, first dose should be given ≥2 weeks before departure
- Single dose provides adequate short-term protection for healthy individuals
Healthcare Workers
- Not routinely recommended, but may be considered based on risk assessment
- Postexposure prophylaxis recommended after exposure to HAV-infected patients
Immunocompromised Individuals
- Vaccination recommended due to increased risk of severe disease
- May have reduced immune response; consider antibody testing post-vaccination
Chronic Liver Disease Patients
- Strongly recommended due to risk of fulminant hepatitis A
- Include patients with chronic hepatitis B or C, cirrhosis, fatty liver disease
Men Who Have Sex with Men
- Recommended due to increased risk of HAV infection
Persons Who Use Injection or Non-injection Drugs
- Recommended due to increased risk of exposure and transmission
Pregnant Women
- Can be given if clearly indicated (e.g., travel to high-risk areas, outbreak settings)
- Postexposure prophylaxis recommended if exposed to HAV
Children
- Routine childhood vaccination recommended in many countries
- Catch-up vaccination for older children in areas with vaccination programs
Public Health Impact
Reduction in Disease Incidence
- 90% decrease in HAV incidence in countries with widespread vaccination programs
- Significant reductions in HAV-related hospitalizations and deaths
Outbreak Control
- Effective in controlling community-wide outbreaks
- Used successfully in postexposure prophylaxis
Herd Immunity
- Evidence of indirect protection in unvaccinated populations
- Reduced HAV circulation in communities with high vaccination coverage
Economic Impact
- Cost-effective intervention, particularly in moderate to high endemicity settings
- Reduction in healthcare costs and productivity losses associated with HAV infection
Global Perspective
- Shifting epidemiology: Decrease in childhood infections, increase in susceptible adults
- WHO recommends integration into national immunization programs for children ≥1 year in countries with intermediate HAV endemicity
Challenges
- Ensuring equitable access in low-income countries
- Maintaining high vaccination coverage in the face of decreasing disease visibility
- Addressing vaccine hesitancy in some populations
Future Directions
- Continued surveillance to monitor long-term vaccine effectiveness
- Research into simplified vaccination schedules (e.g., single-dose regimens)
- Integration of HAV vaccination with other public health interventions (e.g., water and sanitation improvements)
Hepatitis A Vaccines
- What causes Hepatitis A?
Hepatitis A virus (HAV) - How is Hepatitis A typically transmitted?
Through contaminated food or water, or close contact with an infected person - At what age is the Hepatitis A vaccine typically given?
First dose at 12-23 months, second dose 6-18 months later - How many doses of the Hepatitis A vaccine are required for full protection?
Two doses - What is the minimum interval between the two doses of Hepatitis A vaccine?
6 months - How long does protection from the Hepatitis A vaccine last?
At least 20 years, possibly lifelong - Can adults get the Hepatitis A vaccine if they weren't vaccinated as children?
Yes, it's recommended for certain high-risk adults - What is the efficacy of the Hepatitis A vaccine?
Over 95% effective after two doses - Can pregnant women receive the Hepatitis A vaccine?
Yes, if the benefits outweigh the potential risks - What are common side effects of the Hepatitis A vaccine?
Soreness at injection site, headache, loss of appetite, tiredness - Is the Hepatitis A vaccine a live vaccine?
No, it's an inactivated vaccine - Can the Hepatitis A vaccine be given with other vaccines?
Yes, it can be administered with other vaccines - Who should consider getting the Hepatitis A vaccine?
Travelers to endemic areas, men who have sex with men, drug users, people with chronic liver disease - Can someone who has had Hepatitis A get the vaccine?
It's not necessary, as they've developed natural immunity - Is there a combination vaccine that includes Hepatitis A?
Yes, there's a combined Hepatitis A and B vaccine - How soon before travel should the Hepatitis A vaccine be given?
At least 2 weeks before departure, preferably earlier - Can the Hepatitis A vaccine treat an active Hepatitis A infection?
No, it's preventive and doesn't treat active infections - Is Hepatitis A vaccine part of the routine childhood immunization schedule in all countries?
No, it varies by country based on disease prevalence - Can immunocompromised individuals receive the Hepatitis A vaccine?
Yes, but they may have a reduced immune response - What is the storage temperature for Hepatitis A vaccines?
2°C to 8°C (35°F to 46°F) - Can Hepatitis A vaccine be given after exposure to the virus?
Yes, if given within 2 weeks of exposure, it can prevent infection - Is there a separate Hepatitis A vaccine for children and adults?
Yes, there are pediatric and adult formulations - What organization recommends Hepatitis A vaccination globally?
The World Health Organization (WHO) - In which year was the first Hepatitis A vaccine licensed?
1995 - Can the Hepatitis A vaccine cause Hepatitis A?
No, it's an inactivated vaccine and cannot cause the disease - Is Hepatitis A vaccine covered by most insurance plans?
Yes, especially for recommended age groups and high-risk individuals - How long after vaccination does it take to develop immunity against Hepatitis A?
About 2-4 weeks after the first dose - Can Hepatitis A vaccine be given to infants younger than 1 year?
Not routinely, but may be considered for high-risk infants - What percentage of people develop protective antibodies after two doses of Hepatitis A vaccine?
Nearly 100% - Is there a need for booster doses after completing the initial Hepatitis A vaccine series?
Generally no, the initial series provides long-lasting protection
