Demographic data and details of maternal HBV infection were collected for all children. Baseline anti-HBs levels were checked for children who were suboptimal responders before administration of the fourth booster dose [intramuscular 10 µg monovalent hepatitis B (Engerix B, GSK, Wavre, Belgium)]. Eight weeks post-booster, HBsAg, HBV DNA, hepatitis B core antibody (anti-HBc) and anti-HBs titres were measured. Children who were non-responders received a repeat three dose vaccine series and were excluded from follow-up. Children whose mothers had hepatitis C virus or HIV infection, or children born before 37 weeks gestation, had a birthweight less than 2.5 kg, or known primary immuno-deficiency, were excluded. Informed consent was obtained from their parents and assent from those older than 6 years. Study was approved by the National Healthcare Group Domain Specific Review Board.

Data were analyzed with SPSS version 25.0. Comparisons were done using Mann Whitney test, and significance was taken as P<0.05.

Thirty-nine children (3 non-responders and 36 suboptimal responders) were eligible for the study; 30 (13 females) were recruited (3 non-responders and 27 suboptimal responders). Mean (SD) age at time of recruitment was 63 (31.5) months. Majority were Chinese (80%). Mean (SD) birth weight was 3.22 (0.26) kg. Twenty-four were breastfed until 9 months, 6 were born via Caesarean section.

Five (16.7%) mothers were HBeAg positive with HBV DNA viral load of >200,000 IU/mL in their third trimester prior to starting tenofovir. Two (6.7%) received tenofovir during the last trimester. There was incomplete data for 9 children; 4 (13.3%) declined booster vaccination and 5 (16.7%) declined blood tests post-booster for personal reasons. Hence, 21 children had both pre and post-booster serological results for analysis. No children had detectable HBV DNA or reactive anti-HBc.

Median (IQR) anti-HBs titers 3 months after completion of the primary vaccine series was suboptimal at 52 (22-77) IU/L. Median (IQR) anti-HBs titers just prior to booster vaccine further dropped to 7 (2-11) IU/L (P<0.05); 3 (10%) children had values <10 IU/L. Mean (SD) time from completion of three-dose vaccine series to booster vaccine was 62.6 (31.1) months. Median (IQR) anti-HBs titer rose significantly to 606 (134-1000) (P<0.05)) IU/L post-booster vaccine. Eighteen children (85.7%) demonstrated good anti-HBs response (>100 IU/L) after the booster dose. Three children (14.3%) continued to have suboptimal response post-booster vaccine (Fig. 1).

Fig. 1 Box plot of anti-HBs versus time points.

Our study demonstrated that 85.7% of children with suboptimal immune response post-primary series achieved anti-HBs >100 IU/L after a single booster dose, supporting the 2018 ACIP guidelines that a single booster is sufficient instead of three repeat doses [5].

We also demonstrated that anti-HBs titers in infants born to hepatitis B carrier mothers, and who had suboptimal antibody titer three months after completing the three-dose primary series, declined further over the next four years. Occult HBV infection was not detected in this population as a cause of suboptimal response. Our small series contributes to supporting evidence for a single booster, which is cheaper and logistically easier, instead of repeating the three dose series. A single booster may also increase adherence to vaccinations and conserve public health resources involved in vaccine administration.

Acknowledgements: Dr Dimple Rajgor for her assistance in literature search, and the writing, editing, formatting, reviewing, and in submitting the manuscript for publication. Ms Ma Ting for her assistance in data analysis.

Contributors: LJM: contributed in investigation, data collection, curation and formal analysis, drafting of the manuscript; LLY: conceptualized, designed, supervised the study, made critical revisions to the drafted manuscript; TMLN: contributed in investigation, data curation, and made critical revisions to the drafted manuscript; HM: contributed in designing the study, formal data analysis and made critical revisions to the drafted manuscript; CSM: conceptualized, designed, supervised, investigated the study, made critical revisions to the drafted manuscript. All authors approved the final version of manuscript, and are accountable for all aspects related to the study.

Funding: KTP-NUCMI Annual Grant call.

Competing interest: None stated.

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