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Long-Term Protection with Two Doses of Inactivated Hepatitis A Vaccine in Children: Implications for Preventing Fulminant Hepatitis in Adulthood

Article For Year 2 Vaccination 9 min read

Tagged Article Hepatitis A Year 2 Vaccination

Authored by GSK Vaxipedia

In this article

Summary

Key points

Hepatitis A risk is shifting toward adolescents and adults due to delayed childhood exposure, increasing the likelihood of symptomatic disease^1,3
Hepatitis A can lead to fulminant hepatitis and ~30,000 deaths annually, underscoring the need for effective prevention strategies³
Two-dose inactivated hepatitis A vaccination induces high seroprotection with strong immune response in children^3,6
Antibody concentrations show an initial decline followed by long-term stabilization, indicating durable immunity⁶
Long-term follow-up demonstrates persistent antibodies for ≥15 years, supporting sustained protection⁶
Modeling predicts >90% seropositivity at 40 years (GMC 95% CI: 487.9) and >85% (GMC 95% CI: 345) at 50 years, suggesting long-lasting immunity⁶
Long-term protection extends into adulthood, helping reduce the risk of severe and fulminant hepatitis later in life^2,6
Overall, two-dose vaccination provides robust, durable protection and supports long-term disease control^3,6

Introduction

Hepatitis A remains highly endemic in many parts of Asia, including India.¹Hepatitis A virus (HAV) is a non-cytopathic, enterically transmitted virus that causes liver injury through immune-mediated mechanisms.²Transmission occurs primarily through the fecal–oral route via contaminated sources.^1,2

Other key transmission routes include:

Close household or community contact
High-risk groups such as men who have sex with men.³

Changing Epidemiological Patterns

In early childhood, HAV infection is frequently asymptomatic, and infection-induced anti-HAV IgG antibodies may persist lifelong and protect against reinfection.²However, improvements in sanitation and hygiene, particularly in urban areas, have delayed natural exposure to the virus.¹

Increased susceptibility in adolescents and adults
Higher likelihood of symptomatic and severe disease in older age groups
Need for enhanced surveillance and preventive strategies

These epidemiological shifts highlight the importance of vaccination in susceptible populations.^1,3

Hepatitis A and Risk of Fulminant Hepatitis

Hepatitis A infection is generally a self-limiting illness, with infection-induced immunity persisting for life.²However, in rare instances, HAV infection can progress to fulminant hepatic failure, a severe and potentially fatal complication.^2,3

Globally, hepatitis A causes approximately 30,000 deaths annually, underscoring its potential severity despite generally favourable outcomes.³

The risk of progression to fulminant hepatitis is higher in certain groups:

Individuals with pre-existing liver disease
Pregnant women

Additionally, while rare, co-infection with hepatitis A and hepatitis E viruses may further increase the risk of severe liver injury and acute liver failure. These observations underscore the importance of early recognition and preventive strategies, including vaccination.^4,5

Global Disease Burden and Vaccination

Although hepatitis A is vaccine-preventable, HAV infection continues to account for a substantial global disease burden, with approximately 200 million infections and 30 million symptomatic illnesses reported annually.³

Available vaccines are highly immunogenic and well tolerated, with flexible dosing schedules and formulations:

Inactivated hepatitis A vaccines (two- or three-dose regimens)
Monovalent HAV vaccines
Combined hepatitis A and B (HAB) vaccines.⁶

Vaccine Effectiveness and Long-Term Protection

Inactivated HAV vaccines provide high seroprotection rates after two doses in healthy children and adolescents. In addition, long-term data indicate that single-dose live-attenuated vaccines are also capable of conferring sustained immunity.³

Long-Term Persistence of Two Doses of Inactivated Hepatitis A Vaccine⁶

This study was conducted to evaluate the long-term persistence of antibodies in children following two doses of the inactivated hepatitis A/B (HAB) vaccine containing 720 EU of HAV antigen per dose, beyond 15 years, and to assess whether the immunological mechanisms triggered by vaccination support longer-term protection. Antibody kinetics were compared descriptively with data from adult cohorts who received either two doses of HAV 1440 EU vaccines or three doses of HAB 720 EU vaccines.

Clinical Outcomes

Comparison of Antibody Persistence Across Different Dose Schedule⁶

Taken from Agrawal et al., 2020.

Fig. 1. Antibody geometric mean concentration by study (TVC cohort). GMC: geometric mean concentration, EU: enzyme linked immunosorbent assay units, HAB: combination hepatitis A and B virus vaccine, HAV: hepatitis A virus vaccine, TVC: total vaccinated cohort.

This figure illustrates the GMCs of anti‑hepatitis A antibodies by study and dose schedule at each follow-up after primary vaccination and states that anti-hepatitis A antibody GMCs at 18 months post-vaccination are high and comparable in both children and adults.

Taken from Agrawal et al., 2020.

Fig. 2 Antibody geometric mean concentration fold change by study (TVC cohort). GMC: geometric mean concentration (enzyme-linked immunosorbent assay units), HAB: combination hepatitis A and B virus vaccine, HAV: hepatitis A virus vaccine, TVC: total vaccinated cohort.

It shows an initial rapid decline in antibody GMCs in the first years after vaccination, followed by a plateau with minimal annual change. This trend is similar across children and adults, indicating stable long-term antibody levels.

Estimation of Persistence Based on Mathematical Modelling Data⁶

Dosage	2 X HAB 720	3 X HAB 720		2 X HAV 1440
Study name	HAB-084	HAB-028	HAB-032	HAV-112	HAV-123
NCT	00875485	01000324	01037114	00291876	00289757
1-month post-schedule completion
n	148	128	152	165	102
GMC (95% CI)	5313.5	6200.0	4620.1	5243.0	3462.7
15 years follow-up
n	98	50	51	128^{^}	62
GMC (95% CI)	414.7	550.1	326.9	389.9	282.6
20 years follow-up
n	-	28	44	114^*	47
GMC (95% CI)	-	487.9	257.3	345.0	330.7
Model predicted
% seropositive 40 years	-	>97%		>90%
% seropositive 50 years	-	-		>85%

GMC: geometric mean antibody concentration, HAB: combination hepatitis A and B virus vaccine, HAV: hepatitis A virus vaccine, n: number of subjects with available results, CI: Confidence interval^.Adapted from Agrawal et al., 2020.

^15.5 Years

*20.5 Years

Table 2 shows that at 15 years post-vaccination, antibody GMCs in adults ranged from 282.6 to 550.1 mEU/mL, while the children’s estimate (414.7) was comparable and fell within adult study ranges. Given similar antibody kinetics, long-term modeling suggests that protection in children is likely sustained, with at least ~85% remaining protected after 50 years.

Conclusion

Vaccination remains a key strategy to prevent hepatitis A disease.^3,6Two doses of inactivated hepatitis A vaccine in childhood provide robust and long-lasting immunity, with antibody responses comparable to those observed in adults up to 15 years post-vaccination.⁶Despite an initial decline, antibody levels stabilize over time, indicating persistent immune protection.⁶Long-term modeling further suggests that a significant proportion of vaccinated individuals may remain protected for up to 50 years.^5,6These findings support the role of routine childhood hepatitis A vaccination in providing long-term protection that may extend into adulthood and help prevent more severe hepatitis A disease later in life, particularly in endemic settings such as India.^2,6

Key Safety Information⁷

Contraindications:

HAVRIX may not be administered to persons with a known hypersensitivity to a component of the vaccine, or to those who have shown signs of hypersensitivity during a previous administration of HAVRIX.

Special warnings and precautions:

As in the case of other vaccines, HAVRIX will not be administered to patients with an acute febrile illness. A common infection does not constitute a contra-indication, however. HAVRIX may contain traces of neomycin. The vaccine will have to be used with caution in patients with a known hypersensitivity to this antibiotic. As with every product administered parenterally, it is recommended to prepare an appropriate medical treatment for immediate use, if an anaphylactic reaction were to occur . HAVRIX may be administered with persons who are HIV positive.

Undesirable Effects:

Very Common - Irritability, drowsiness, headache, pain and redness at injection site.

References:

Trivedi C, Marathe S, Bhat N, Karadkhele A, Puppalwar G, Jain R. Clinician's perspective on the use of hepatitis A vaccine in Indian children. Pediatr Infect Dis. 2019;1(4):148-153. doi:10.5005/jp-journals-10081-1228.
Gholizadeh O, Akbarzadeh S, Ghazanfari Hashemi M, et al. Hepatitis A: Viral Structure, Classification, Life Cycle, Clinical Symptoms, Diagnosis Error, and Vaccination. Can J Infect Dis Med Microbiol. 2023;2023:4263309. Published 2023 Jan 4. doi:10.1155/2023/4263309
Herzog C, Van Herck K, Van Damme P. Hepatitis A vaccination and its immunological and epidemiological long-term effects - a review of the evidence. Hum Vaccin Immunother. 2021;17(5):1496-1519. doi:10.1080/21645515.2020.1819742.
Hepatitis A. World Health Organization. 2025. Accessed May 6, 2026.
Malik H, Malik H, Uderani M, Berhanu M, Soto CJ, Saleem F. Fulminant Hepatitis A and E Co-infection Leading to Acute Liver Failure: A Case Report. Cureus. 2023;15(4):e38101. Published 2023 Apr 25. doi:10.7759/cureus.38101
Agrawal A, Kolhapure S, Andani A, et al. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020;9(4):785-796. doi:10.1007/s40121-020-00311-8.
Havrix, Prescribing Information, Version: HAX/PI/IN/2024/01 Dated 10-Jun-2024. https://india-pharma.gsk.com/media/qqmlvec5/havrix.pdf

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For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information. Please report adverse events with any GSK product to the company at [email protected]. © 2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).

CL Code: PM-IN-HAV-WCNT-260008 | DOP: June 2026

For more information, please refer the following link

https://india-pharma.gsk.com/media/qqmlvec5/havrix.pdf

For Indian Healthcare Professionals Only

Key Safety Information

Contraindications:

HAVRIX may not be administered to persons with a known hypersensitivity to a component of the vaccine, or to those who have shown signs of hypersensitivity during a previous administration of HAVRIX.

Special warnings and precautions:

As in the case of other vaccines, HAVRIX will not be administered to patients with an acute febrile illness. A common infection does not constitute a contra-indication, however. HAVRIX may contain traces of neomycin. The vaccine will have to be used with caution in patients with a known hypersensitivity to this antibiotic. As with every product administered parenterally, it is recommended to prepare an appropriate medical treatment for immediate use, if an anaphylactic reaction were to occur. HAVRIX may be administered with persons who are HIV positive.

Undesirable Effects:

Very Common - Irritability, drowsiness, headache, pain and redness at injection site

For the use only of Registered Medical Practitioners or a Hospital or a Laboratory

Abbreviated Prescribing information of HAVRIX 1440 (ADULT) / 720 (JUNIOR)

Inactivated Hepatitis A Vaccine (Adsorbed) IP

ACTIVE INGREDIENT: HAVRIX1440: Each dose (1 ml) contains: Hepatitis A virus antigen (HAV) HM 175 strain, 1440 ELISA units (ELU); Aluminium (as aluminium hydroxide) 0.5 mg. HAVRIX720: Each dose (0.5 ml) contains: Hepatitis A virus antigen (HAV) HM 175 strain, 720 ELISA units (ELU); Aluminium (as aluminium hydroxide) 0.25 mg.

INDICATION: For active immunisation against infections caused by hepatitis A virus (HAV) for Children and Adolescents (from 1 year up to and including 18 years of age) and adults (from age 19 years and onwards). The booster dose may be given at any time between 6 months and 5 years, but preferably between 6 and 12 months after the primary dose.

DOSAGE AND ADMINISTRATION: Primary vaccination- Adults from age 19 years and onwards: A single dose of HAVRIX 1440 Adult (1.0 mL suspension) is used for primary immunisation. - Children and adolescents from 1 year up to and including 18 years of age: A single dose of HAVRIX 720 Junior (0.5 mL suspension) is used for primary immunisation. Booster vaccination- After primary vaccination with either HAVRIX 1440 Adult or HAVRIX 720 Junior, a booster dose is recommended in order to ensure long term protection. This booster dose should be given at any time between 6 months and 5 years, but preferably between 6 and 12 months after the primary dose. Method of Administration- HAVRIX must be injected intramuscularly only. It is recommended to inject the vaccine in the deltoid region in adults and in children. The deltoid muscle is not yet sufficiently developed in very young children, so the vaccine should be administered in the anterolateral part of the thigh. The injection must not be administered in the gluteal region subcutaneously or intradermally because the antibody response might be sub-optimal. However, the vaccine should be administered subcutaneously in patients suffering from thrombocytopoenia or subject to serious haemorrhage (e.g. haemophiliacs) because bleeding could occur after intramuscular administration in such persons. Strong pressure should be exercised at the site of the injection (without rubbing) for at least 2 minutes. The vaccine may never be administered intravascularly.

CONTRA-INDICATIONS: HAVRIX may not be administered to persons with a known hypersensitivity to a component of the vaccine or to those who have shown signs of hypersensitivity during a previous administration of HAVRIX.

SPECIAL WARNINGS and SPECIAL PRECAUTIONS: As in the case of other vaccines, HAVRIX will not be administered to patients with an acute febrile illness. A common infection does not constitute a contra-indication, however. People may already be in the incubation period of hepatitis A at the time of vaccination. In such circumstances, it is not certain that HAVRIX will prevent hepatitis A.

In patients undergoing haemodialysis and in subjects with a deficient immune system, the anti-HAV (hepatitis A virus) may remain insufficient after a primo-vaccination; in such patients, additional doses of the vaccine may have to be administered to attain an adequate antibody count. HAVRIX may contain traces of neomycin. The vaccine will have to be used with caution in patients with a known hypersensitivity to this antibiotic. As with every product administered parenterally, it is recommended to prepare an appropriate medical treatment for immediate use, if an anaphylactic reaction were to occur after the administration of the vaccine. For this reason, the vaccinated persons should remain under medical supervision for half an hour after vaccination. Syncope (fainting) can occur after any vaccination, or even before with adolescents in particular, as a psychogenic reaction to injection. This can be accompanied by several neurological signs such as a transient disturbance in vision, paraesthesia and tonic clonic movements of the limbs during the recovery phase. It is important that caution be set up to avoid injuries in the event of fainting. HAVRIX may be administered with persons who are HIV positive. Vaccination is not justified in subjects with anti-hepatitis A IgG.

This vaccine contains less than 1 mmol of sodium (23 mg) per dose, it is therefore essentially ‘sodium-free’. This vaccine contains potassium, less than 1 mmol (39 mg) per dose, it is therefore essentially ‘potassium-free’.

ADVERSE EFFECTS:

Clinical Trials: Frequencies, per dose, are defined as follows: Very common: ≥ 1/10, Common: ≥ 1/100 to < 1/10, Uncommon: ≥1/1000 to < 1/100, Rare: ≥1/10000 to < 1/1000, Very rare: < 1/10000.

Undesirable effects reported with HAVRIX Junior 720

Infections and infestations Uncommon: rhinitis. Metabolism and nutrition disorders Common: loss of appetite. Psychiatric disorders Very common: irritability. Nervous system disorders Common: drowsiness, headaches Very rare: neuritis, including Guillain-Barré syndrome and transverse myelitis. Gastrointestinal disorders_Common: nausea Uncommon: diarrhoea, vomiting Skin and subcutaneous tissue disorders Uncommon: rash General disorders and administrative site conditions Very common: pain and redness at injection site Common: swelling, malaise, fever (> 37.5°C) Uncommon: reaction at the injection site (induration)

Undesirable effects reported with HAVRIX 1440

Infections and infestations: Uncommon: upper respiratory tract infection, rhinitis Metabolism and nutrition disorders: Common: loss of appetite Nervous system disorders: Very common: headaches Uncommon: dizziness Rare: hypoaesthesia, paraesthesia Very rare: neuritis, including Guiliain-Barré syndrome and transverse myelitis. Gastrointestinal disorders: Common: gastrointestinal syndromes, diarrhoea, nausea Uncommon: vomiting Skin and subcutaneous tissue disorders Rare: pruritis Musculoskeletal and systemic disorders: Uncommon: myalgia, musculoskeletal stiffness General disorders and administrative site conditions: Very common: pain and redness at injection site, fatigue Common: swelling, malaise, fever (>37.5°C), reaction at the injection site (induration) Uncommon: influenza like illness Rare: shivering

Post-marketing surveillance

Immune system disorders: Anaphylactic reactions, allergic reactions, including anaphylactoid reactions and serum sickness like disease. Nervous system disorders: Convulsions Vascular disorders: Vasculitis Skin and subcutaneous tissue disorders: Angioneurotic oedema, urticaria, erythema multiforme Musculoskeletal and connective tissue disorders: Arthralgia

Version: HAX/API/IN/2025/02 v02 dated 03 Jul 2025

Registered medical practitioners can refer company website http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information.

Please report adverse events with any GSK product to the company at [email protected]

For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website: india-pharma.gsk.com/en-in/products/prescribing-information/ for Full Product Information. Please report adverse events with any GSK product to the company at [email protected]. ©2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).