DTwP-HB-Hib: antibody persistence after a primary series, immune response and safety after a booster dose in children 18-24 months old

Hartono Gunardi, Kusnandi Rusmil, Eddy Fadlyana, Soedjatmiko, Meita Dhamayanti, Rini Sekartini, Rodman Tarigan, Hindra Irawan Satari, Bernie Endyarni Medise, Rini Mulia Sari, Novilia Sjafri Bachtiar, Cissy B Kartasasmita, Sri Rezeki S Hadinegoro, Hartono Gunardi, Kusnandi Rusmil, Eddy Fadlyana, Soedjatmiko, Meita Dhamayanti, Rini Sekartini, Rodman Tarigan, Hindra Irawan Satari, Bernie Endyarni Medise, Rini Mulia Sari, Novilia Sjafri Bachtiar, Cissy B Kartasasmita, Sri Rezeki S Hadinegoro

Abstract

Background: The new combination of DTwP-HB-Hib vaccines has been developed in Indonesia following World Health Organization (WHO) recommendation and integrated into national immunization program. The aims of the study were to measure 1) antibody persistence 12-18 months after a primary series, 2) immune response and safety after a booster dose of DTwP-HB-Hib.

Methods: This was a multi-center, open-labeled, prospective, interventional study. Subjects who had received complete primary dose of DTwP-HB-Hib vaccine from the previous phase III trial were recruited in this trial. Subjects were given one dose of DTwP-HB-Hib (Pentabio®) booster at age 18-24 months old. Diphtheria, tetanus, pertussis, hepatitis B, Hemophilus influenza type B antibodies were measured before and after booster to determine antibody persistence and immune response. Vaccine adverse events were assessed immediately and monitored until 28 days after the booster recorded with parent's diary cards.

Results: There were 396 subjects who completed the study. Increased proportion of seroprotected subjects from pre-booster to post-booster were noted in all vaccine antigens: 74.5 to 99.7% for diphtheria; 100 to 100% for tetanus; 40.4 to 95.5% for pertussis; 90.2 to 99.5% for hepatitis B; and 97.7 to 100% for Hib. Common systemic adverse events (AEs) were irritability (23.7-25%) and fever (39.9-45.2%). Local AEs such as redness, swelling, and induration were significantly less common in the thigh group (7.7, 11.3, and 7.1%) than in the deltoid group (28.9, 30.7, and 25%) (P < 0.001). Most AEs were mild and resolved spontaneously within three-day follow-up period.

Conclusions: Booster of DTwP-HB-Hib vaccine at age 18-24 months is required to achieve and maintain optimal protective antibody. The vaccine is safe and immunogenic to be used for booster vaccination.

Trial registration: NCT02095314 (retrospectively registered, March 24, 2014).

Keywords: Booster dose; Children; DTwP-HB-Hib vaccine; Immunogenicity; Safety.

Conflict of interest statement

Ethics approval and consent to participate

This trial has been approved by Health Research Ethics Committee Faculty of Medicine Universitas Padjajaran Bandung (418/UN6.C2.1.2/KEPK/PPN/2013) and The Ethics Committee of the Faculty of Medicine, University of Indonesia (735/H2.F1/ETIK/2013).

A written form of informed consent was obtained from every child’s parent or legal guardian before the recruitment.

Competing interests

Hartono Gunardi, Kusnandi Rusmil, Eddy Fadlyana, Soedjatmiko, Meita Dhamayanti, Rini Sekartini, Rodman Tarigan, Hindra Irawan Satari, Bernie Endyarni Medise, Cissy B Kartasasmita, Sri Rezeki S Hadinegoro, received grant support through their institutions. Rini Mulia Sari and Novilia Sjafri Bachtiar were employees of PT Bio Farma at the time of the conduct of this study and manuscript preparation.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Subjects recruitment
Fig. 2
Fig. 2
Local and systemic adverse events *local and systemic adverse events 30 minutes – 72 hours, #Systemic adverse events 72 hours – 28 days, No significant differences in AEs for pain, irritability, and others between deltoid and thigh group

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