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Antibody Persistence After Infant Hexavalent Vaccination: Long-Term Follow-Up Snapshot

Article For Year 1 Vaccination 11 min read

Authored by GSK Vaxipedia

In this article

Summary

Key points

Long-term follow-up shows sustained antibody persistence up to 6.4 years post-booster after infant hexavalent vaccination²
In children aged 7–9 years, seroprotection remains high for poliovirus (≥91%, GMTs: Type 1: 51.9 (95% CI: 40.9–65.8), Type 2: 43.6 (95% CI: 34.7–54.8), Type 3: 96.4 (95% CI: 75.1–123.9)) and Hib (~99.5%, GMC: 1.584 µg/mL (95% CI: 1.330–1.886)), indicating durable immunity²
Protective antibody levels persist for diphtheria (~86%, GMC: 0.23 IU/mL (95% CI: 0.153–0.346)) and hepatitis B (~77%, GMC: 42.1 mIU/mL (95% CI: 33.4–53.0)), even in the absence of recent boosting²
Pertussis antibody levels decline over time (anti-PT ~32%, GMC: 4.9 EL.U/mL (95% CI: 4.1–6.0)), consistent with known waning patterns without natural exposure²
Administration of additional boosters is associated with higher seroprotection rates for diphtheria and tetanus, supporting booster strategies²
Detectable protection extends for up to 9 years post-primary vaccination, particularly for Hib and poliovirus components²
Declining circulating antibodies do not equate to loss of protection, as immunological memory supports rapid anamnestic response²

Importance of Durable Immune Persistence After Infant Vaccination

Vaccination is a cornerstone of childhood disease prevention and remains one of the most effective and cost-efficient strategies for controlling infectious diseases globally.¹As pediatric immunization schedules have expanded, combination vaccines have been developed to simplify vaccine delivery by incorporating multiple antigens into a single formulation.¹This approach reduces the number of injections and clinic visits required to complete immunization while maintaining immunogenicity and safety.¹Hexavalent combination vaccines containing diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b (Hib) antigens provide protection against six major childhood diseases through a single injection.²These vaccines are typically administered as a primary infant series followed by a booster dose in the second year of life and have demonstrated good immunogenicity and tolerability in infants and toddlers.^1,2Beyond the initial immune response, hexavalent vaccination has been shown to elicit antibody responses that persist into early childhood, with sustained immunity observed for several vaccine antigens years after completion of the infant schedule.^2-4

Clinical Assessment of Antibody Persistence After Infant Hexavalent Immunization

Study design and population²

Design: Long-term serological follow-up study conducted in Germany
Participants: Children previously primed with a 3-dose infant series and boosted in the second year of life with a hexavalent DTPa-HBV-IPV/Hib vaccine
Total enrolled: 200 children; 193 included in the according-to-protocol persistence cohort

Follow-up interval: 6.4 years after the administration of the fourth vaccine dose

Antibody persistence in children aged 7–9 years²

A proportion of children had received additional booster vaccinations between the toddler booster and follow-up, in accordance with national immunization recommendations for diphtheria and tetanus.

In non-boosted children:

In children aged 7–9 years without additional booster vaccination, high seroprotection was maintained for Haemophilus influenzae type b and poliovirus (≥91%), with sustained protective antibody levels also observed for diphtheria and hepatitis B. These findings are consistent with long-term follow-up studies demonstrating durable antibody persistence across vaccine antigens, while lower anti-pertussis toxin levels reflect the expected kinetics of pertussis-specific immune responses in the absence of natural exposure.²

Children who received additional booster doses demonstrated higher seroprotection rates for diphtheria and tetanus, consistent with booster-induced increases in antibody levels.²

Protective antibody responses remained detectable for several vaccine antigens up to 9 years after infant vaccination, with particularly strong persistence observed for Hib and poliovirus.²

Antibody concentrations²

Geometric mean antibody concentrations/titres (GMC/GMT) were assessed to further characterize immune persistence in both age cohorts.²

Table: Persistence of antibodies in non-boosted children 7–9 years of age who had previously received primary and booster vaccination with DTPa-HBV-IPV/Hib²

Antibody	N	GMC/GMT	95% CI (LL–UL)	Cut-offs indicating seroprotection
Anti-diphtheria	51*	0.23	0.153–0.346	0.016 IU/mL (Vero cell assay)
Anti-tetanus	51*	0.335	0.195–0.574	0.1 IU/mL
Anti-PRP	193	1.584	1.330–1.886	0.15 μg/mL
Anti-HBs	193	42.1	33.4–53.0	10 mIU/mL
Anti-PT	161*	4.9	4.1–6.0	5 EL.U/mL
Anti-FHA	161*	57	47.2–68.9	5 EL.U/mL
Anti-PRN	162*	20.2	16.3–25.0	5 EL.U/mL
Anti-Polio type 1	145*	51.9	40.9–65.8	Titre 8 (microneutralisation)
Anti-Polio type 2	148*	43.6	34.7–54.8	Titre 8 (microneutralisation)
Anti-Polio type 3	144*	96.4	75.1–123.9	Titre 8 (microneutralisation)

GSK has created this table by referring the Zinke et al., 2010article²

N, number of children with available results; 95% CI, 95% confidence interval; LL/UL, lower and upper limits; GMC/GMT, geometric mean antibody concentration/titre (IU/mL); IU/mL, international units per millilitre; mIU/mL, milli-international units per millilitre; μg/mL, micrograms per millilitre; EL.U/mL, ELISA units per millilitre; ELISA, enzyme-linked immunosorbent assay; PT, pertussis toxin; FHA, filamentous haemagglutinin; PRN, pertactin; PRP, polyribosylribitol-phosphate; Hib, Haemophilus influenzae type b; HBs, hepatitis B surface antigen; DTPa-HBV-IPV/Hib, combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b conjugate vaccine; CoP, correlate of protection; VPD, vaccine-preventable disease;

*Number of subjects who had not received the booster dose of the specified antigen after the booster in second year of life.

Discussion

Long-term follow-up indicates sustained antibody persistence for multiple vaccine antigens following completion of the infant hexavalent vaccination schedule. In children aged 7–9 years, high seroprotection was maintained for Haemophilus influenzae type b and poliovirus, with protective antibody levels also retained for diphtheria and hepatitis B in a substantial proportion of individuals.²These findings demonstrate continued immune persistence several years after primary immunization and the toddler booster dose.²A decline in antibody concentrations over time was observed, consistent with the expected kinetics of waning circulating antibodies as the interval from vaccination increases. Importantly, declining antibody levels may not necessarily indicate loss of protection, as evidence of persistent vaccine effectiveness and cell-mediated immune responses has been observed despite lower circulating antibody concentrations.²The observed persistence patterns are consistent with evidence from other longitudinal studies of hexavalent vaccination.^3,4For instance, long-term evaluation of children vaccinated with a hexavalent schedule showed that 86.9% retained protective hepatitis B surface antibody levels at 7 years of age.³Similarly, a study assessing antibody persistence after hexavalent vaccination demonstrated good persistence of antibodies across all vaccine antigens up to pre-school age.⁴

Key Safety Information⁵

Contraindications

Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.

Special warnings and precautions

Carefully consider decision to give further doses if: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Administer with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13.

Special populations

HIV infection not a contraindication. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity.

Pregnancy and Lactation

INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Undesirable effects

Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness

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

References

Liu B, Cao B, Wang C, et al. Immunogenicity and Safety of Childhood Combination Vaccines: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2022;10(3):472. Published 2022 Mar 18. doi:10.3390/vaccines10030472.
Zinke M, Disselhoff J; DTP a-HBV-IPV-110 and -111 study groups, Gartner B, Jacquet JM. Immunological persistence in 4-6- and 7–9-year-olds previously vaccinated in infancy with hexavalent DTPa-HBV-IPV/Hib. Hum Vaccin. 2010;6(2):189-193. doi:10.4161/hv.6.2.10117
Wanlapakorn N, Sarawanangkoor N, Srimuan D, Thatsanathorn T, Klinfueng S, Poovorawan Y. Persistence of hepatitis B surface antibody until 7 years of age following administration of hexavalent and pentavalent vaccines in children at 2, 4, 6, and 18 months. Vaccine X. 2024;20:100561. Published 2024 Sep 20. doi: 10.1016/j.jvacx.2024.100561
Madhi SA, López P, Zambrano B, et al. Antibody persistence in pre-school children after hexavalent vaccine infant primary and booster administration. Hum Vaccin Immunother. 2019;15(3):658-668. doi:10.1080/21645515.2018.1546524
Infanrix Hexa Version: IFX-H/PI/IN/2025/01 Revised on: 09-Dec-2025. https://india-pharma.gsk.com/media/a3hbdio3/infanrixhexa.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-INH-WCNT-260011 | DOP: June 2026

For more information, please refer the following link

https://india-pharma.gsk.com/media/a3hbdio3/infanrixhexa.pdf

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Key Safety Information

Contraindications

Special warnings and precautions

Special populations

Pregnancy and Lactation

INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Undesirable effects

Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness

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

Abbreviated Prescribing information of INFANRIX HEXA [Diphtheria, tetanus, pertussis (acellular component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed) Ph. Eur.]

ACTIVE INGREDIENT: Each 0.5 ml dose of reconstituted vaccine contains (i) Diphtheria toxoid ≥ 30 IU, (ii) Tetanus toxoid ≥ 40 IU, (iii) Bordetella pertussis antigens (Pertussis toxoid 25mcg, Filamentous Haemagglutinin 25 mcg, Pertactin 8 mcg), (iv) Hepatitis B surface antigen 10 mcg, (v) Inactivated Poliovirus [type 1 (Mahoney strain) 40 D-antigen unit, type 2 (MEF-1 strain) 8 D-antigen unit, type 3 (Saukett strain) 32 D-antigen unit), (vi) Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate, PRP) 10 mcg conjugated to tetanus toxoid as carrier protein (approximately 25 mcg).

INDICATION: Primary and booster vaccination of infants against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b.

DOSAGE AND ADMINISTRATION: Posology: The primary vaccination schedule should be administered according to official recommendations. Full-term infants or Preterm infants (≥24 weeks gestational age): 3-dose primary vaccination: interval of ≥1 month between primary doses. Booster dose ≥6 months after last priming dose; preferably ≤18 months of age. 2-dose primary vaccination: interval of ≥2 month between primary doses. Booster dose ≥6 months after last priming dose; preferably between 11-13 months of age. Administered according to official recommendations. The Expanded Program on Immunisation schedule (at 6, 10, 14 weeks of age) may only be used if hepatitis B vaccine given at birth. Safety and efficacy not been established in children > 36 months of age. Method of Administration: Deep intramuscular injection, preferably at alternating sites for subsequent injections.

CONTRA-INDICATIONS: Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.

SPECIAL WARNINGS and SPECIAL PRECAUTIONS: Precede vaccination by review of medical history and clinical examination. Protective immune response may not be elicited in all vaccinees. Will not prevent disease caused by pathogens other than Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. However, Hepatitis D can be expected to be prevent. If any following events have occurred in temporal relation to receipt of pertussis-containing vaccine, carefully considered decision to give further doses of pertussis-containing vaccines: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Appropriate medical treatment and supervision be available in case of rare anaphylactic event. Carefully weigh risk-benefit of immunising or deferring vaccination in infant or child suffering from new onset or progression of severe neurological disorder. Administered with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. History of febrile convulsions, family history of convulsions or Sudden Infant Death Syndrome (SIDS) not a contraindication for use. Vaccinees with history of febrile convulsions should be closely followed up. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13. Antipyretic treatment should be initiated according to local treatment guidelines. Special populations: HIV infection not a contraindication. Expected immunological response may not be obtained in immunosuppressed patients. Can be given to preterm infants; however lower immune response been observed for some antigens. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity. Benefit of vaccination is high; vaccination should not be withheld or delayed. Interference with laboratory testing: Hib capsular polysaccharide antigen excreted in urine, positive urine test observed within 1-2 weeks. Interaction with other medicinal products and other forms of interaction: INFANRIX HEXA can be given concomitantly with pneumococcal conjugate vaccine (PCV7, PCV10 and PCV13), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral rotavirus vaccine and measles-mumps-rubella-varicella (MMRV) vaccine. Pregnancy and Lactation: INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

ADVERSE EFFECTS: The following drug-related adverse reactions were reported in clinical studies (data from more than 16,000 subjects) and during post-marketing surveillance.

Very common (≥1/10): Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness.

Common (≥1/100 to <1/10): Nervousness, diarrhoea, vomiting, fever >39.5°C, injection site reactions, including induration, local swelling at the injection site (>50 mm).

Uncommon (≥1/1,000 to <1/100): Upper respiratory tract infection, cough, diffuse swelling of the injected limb, sometimes involving the adjacent joint, fatigue.

Rare (≥1/10,000 to <1/1,000): Lymphadenopathy, thrombocytopenia, anaphylactic reactions, anaphylactoid reactions (including urticaria), allergic reactions (including pruritus), collapse or shock-like state (hypotonic-hyporesponsive episode), bronchitis, apnoea, rash, angioedema, swelling of the entire injected limb, extensive swelling reactions, injection site mass, injection site vesicles.

Very rare (<1/10,000): Appetite lost, Convulsions (with or without fever), dermatitis.

OVERDOSE: No cases of overdose reported.

Version: IFX-H/API/IN updated on 10 May 2023.

Registered medical practitioners can refer company website www.gsk-india.com/product-prescribing-information.aspx 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).