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Hepatitis A Vaccines in Children: Immunogenicity and Interchangeability Trial Evidence

Hepatitis A Vaccines in Children: Immunogenicity and Interchangeability Trial Evidence

Article For Year 2 Vaccination 7 min read
Tagged Article Hepatitis A Year 2 Vaccination
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Authored by GSK Vaxipedia
Havrix
In this article
Summary

Key points

  • Hepatitis A remains a significant disease burden, with ~100 million infections and 15,000–30,000 deaths annually worldwide1
  • In India, ~44.5% of children ≤15 years remain susceptible, indicating a shift toward increased infection risk in older age groups4
  • A randomized study in 332 HAV-seronegative children (1–15 years) demonstrated strong immunogenicity following vaccination7
  • Rapid seroconversion is achieved after a single dose, with ~99.4 (311 mIU/mL (95% CI: 274–353)) to 100% (GMC:138 mIU/mL (95% CI: 120–159)) seroprotection by Day 147
  • Two-dose schedules result in 100% seroconversion (GMCs: 8537 mIU/mL (homologous schedule),4008 mIU/mL (alternative schedule), 7144 mIU/mL (mixed schedule)) confirming a robust booster response across all groups7
  • High antibody titres post-booster (GMCs up to ~8537 mIU/mL) indicate strong and sustained immune response7
  • Comparable immunogenicity with mixed and homologous schedules supports interchangeability of hepatitis A vaccines6,7
  • Vaccination is well tolerated, with mainly mild adverse events and no vaccine-related serious adverse events reported7
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Introduction

Hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide and remains an important public health concern despite improvements in sanitation and vaccination programs.1 HAV is a positive-sense RNA virus belonging to the Hepatovirus genus of the Picornaviridae family and is transmitted mainly through the fecal–oral route via person-to-person contacts or consumption of contaminated food or water.1,2 Less frequently, transmission can occur through contaminated blood products or organ transplantation.2 HAV infection causes a considerable global disease burden. Approximately 100 million infections occur annually, including around 1.5 million symptomatic cases and 15,000–30,000 deaths worldwide.1

Clinical manifestations vary by age. Infection is frequently asymptomatic in children, with more than 90% of infections in children younger than six years producing minimal symptoms, whereas over 70% of adults develop symptomatic disease, often presenting with jaundice.1 Disease severity increases with age, among symptomatic adults, jaundice is present in 70–80% of cases.3

Evolving Epidemiology and the Need for Long-Term Protection

The epidemiology of hepatitis A in India has undergone a notable transition, driven by improvements in sanitation, hygiene, and socioeconomic conditions. Data from a multicentric study by Lalwani S et al., conducted across Pune, Kolkata, Chennai, and Ludhiana, demonstrate a clear shift in seroepidemiological patterns.4

Only 44.9% of children ≤5 years were anti-HAV positive, increasing to 92.9% in adults aged 26–40 years. Importantly, 44.5% of individuals ≤15 years were anti-HAV negative and therefore susceptible to HAV infection.4 While Pune, Chennai, and Ludhiana show intermediate endemicity, Kolkata reflects low endemicity. Longitudinal data from Pune highlight a shift from high to intermediate endemicity between 1982 and 2022, initially in higher socioeconomic groups and later extending to lower-middle strata, indicating delayed acquisition of natural immunity.4

With improvements in sanitation and reduced childhood exposure to hepatitis A virus, a larger proportion of the population remains susceptible later in life.4,5 In regions transitioning from high to intermediate endemicity, the World Health Organization recommends consideration of hepatitis A vaccination in routine childhood immunization programmes based on epidemiological and endemicity patterns.5,6

Immunogenicity in Children: Evidence from a Randomized Trial

A randomized clinical trial conducted in Chile evaluated the immunogenicity of two inactivated hepatitis A vaccines derived from different viral strains in 332 HAV-seronegative children aged 1–15 years.7

  • Viral strains: GBM (Group A)8 vs HM175 (Group B)9
  • Participants were stratified by age and randomized to receive two doses administered six months apart.7
  • Children received either a homologous schedule (same vaccine for both doses) or a mixed schedule in which the second dose differed from the first.7

A single vaccine dose produced a rapid immune response. Within 14 days, nearly all children developed detectable anti-HAV antibodies, indicating strong early immunogenicity.7

Immunogenicity was quantified by geometric mean concentration (GMC) of anti-HAV antibodies (mIU/mL); all reported values exceeded the accepted seroprotection threshold of ≥20 mIU/mL. Participants were stratified into three age groups; immune responses were consistent across strata.7

Immune Response After the First Dose7

Booster Response After the Second Dose7

Antibody concentrations declined modestly during the six-month interval between doses, but almost all children remained seroconverted before receiving the booster dose. The second dose elicited a robust antibody response across all vaccination schedules.

No non-responders were observed following the second dose, indicating effective immune priming and a strong booster response regardless of schedule.

Safety and Reactogenicity

Both vaccines were well tolerated, with most adverse events mild to moderate and resolving within a few days. Immediate reactions were uncommon (2–6%). The most frequent local reaction was injection-site pain (36–44% after the first dose), while systemic events such as headache and asthenia occurred in 38–40% of children and were less common after the second dose, consistent with reactogenicity profiles reported for other inactivated vaccines. No serious adverse events were vaccine-related, and no participants withdrew due to safety concerns.7

Conclusion

Inactivated hepatitis A vaccination in children demonstrates strong immunogenicity and a well-tolerated safety profile.7 The randomized trial showed rapid seroconversion following the first dose and a robust booster response after the second dose, indicating effective immune priming.7 Importantly, comparable immune responses were observed with both homologous and mixed vaccination schedules, supporting the interchangeability of vaccines within the two-dose series.6,7 These findings reinforce the role of pediatric hepatitis A vaccination as an effective strategy to ensure early and sustained protection, particularly in regions experiencing a shift in hepatitis A epidemiology toward older age groups.4-6

Key Safety Information8

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

References

  1. Migueres M, Lhomme S, Izopet J. Hepatitis A: Epidemiology, High-Risk Groups, Prevention and Research on Antiviral Treatment. Viruses. 2021;13(10):1900. Published 2021 Sep 22. doi:10.3390/v13101900.
  2. Xu Y, Xiao L, Zhou X, et al. Regional and age-related variations in hepatitis A virus incidence in China 2004 to 2018: a descriptive epidemiological study. Sci Rep. 2025;15:19230. doi:10.1038/s41598-025-03649-6.
  3. UK Health Security Agency. Hepatitis A. In: Immunisation Against Infectious Disease (The Green Book). Chapter 17. Updated January 12, 2024. Accessed May 2, 2026. https://www.gov.uk/government/publications/hepatitis-a-the-green-book-chapter-17
  4. Lalwani S, Palkar S, S B, et al. Age-stratified prevalence of anti-hepatitis A virus antibodies in four metropolitan Indian cities and recent changes in Pune city. Indian J Gastroenterol. Published online March 7, 2025. doi:10.1007/s12664-025-01746-y
  5. Majeed AA, Sarfraz M, Butt AS. Evolving trends in hepatitis A epidemiology: Shifting patterns, emerging risks, and future strategies. World J Virol. 2025;14(4):112590. doi:10.5501/wjv.v14.i4.112590
  6. World Health Organization. Hepatitis A vaccines: WHO position paper—June 2012. Wkly Epidemiol Rec. 2012;87(28-29):261-276. Accessed May 2, 2026. https://www.who.int/publications/i/item/who-wer8728-29-261-276
  7. Abarca K, Ibánez I, Perret C, Vial P, Zinsou JA. Immunogenicity, safety, and interchangeability of two inactivated hepatitis A vaccines in Chilean children. Int J Infect Dis. 2008;12(3):270-277. doi:10.1016/j.ijid.2007.08.006
  8. Havrix Prescribing Information, Version: HAX/PI/IN/2024/01 Dated 10-Jun-2024. https://india-pharma.gsk.com/media/qqmlvec5/havrix.pdf

GSK is not responsible for the third-party website content

Disclaimer

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-260007 | 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).