The Safety and Immunogenicity of Two Hepatitis B Vaccine Formulations (Thiomersal-free and Thiomersal-containing) in Healthy Vietnamese Infants: A Phase III, Prospective, Single-blinded, Randomized, Controlled Trial

Hieu, Nguyen Trong MD*; Sarnecki, Michal MD; Tolboom, Jeroen MSc

Pediatric Infectious Disease Journal: January 2015 - Volume 34 - Issue 1 - p 79–83
doi: 10.1097/INF.0000000000000479
Vaccine Reports

Background: To evaluate the safety and immunogenicity of the thiomersal-free (TF) and thiomersal-containing (TC) formulations of Hepavax-Gene in healthy Vietnamese neonates.

Methods: A single-blind, randomized, controlled study in Ho Chi Minh City, Vietnam. Healthy infants, born after a normal gestational period (37–42 weeks) to hepatitis B surface antigen-negative mothers, participated in the study. Subjects were randomly allocated in a 1:1 ratio to receive either Hepavax-Gene TC or Hepavax-Gene TF using a standard 0–1–6-month administration schedule. Postvaccination blood samples were taken at months 1, 6 and 7. Parents/legal guardians recorded solicited local and systemic adverse events up to 4 weeks after each vaccination.

Results: Very high proportions of subjects were seroprotected. Seroprotection rates at 1, 6 and 7 months were all above 95% using a 10 IU/L cutoff, and were mostly above 90% using a 100 IU/L cutoff. Seroprotection rates between the 2 formulations were equivalent within a 5% margin for either cutoff titer both after 6 and 7 months. There were no significant differences in the number of adverse events reported between the 2 formulations. Safety results were in line with previous reports for Hepavax-Gene. Both formulations of Hepavax-Gene were well tolerated. There were no local adverse events reported in the TF group. No serious adverse events were reported during the study.

Conclusions: The thiomersal-free formulation of Hepavax-Gene was noninferior to the thiomersal-containing formulation of Hepavax-Gene in terms of immunogenicity. There was evidence that the thiomersal-free vaccine was associated with fewer local adverse events.

From the *Hung Vuong Hospital, Ho Chi Minh City, Vietnam; Crucell Switzerland AG, Bern, Switzerland; and Crucell Holland BV, CN Leiden, The Netherlands.

Accepted for publication June 9, 2014.

Crucell Switzerland AG was involved in analysis and interpretation of data, writing of the report and in the decision to submit the article for publication.

J.T. is an employee of Crucell Holland BV and M.S. of Crucell Switzerland AG. N.T.H. received funding for the study from Berna Biotech Korea Corporation (Crucell).

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Address for correspondence: Michal Sarnecki, MD, Crucell Switzerland AG, Rehhagstrasse 79, 3018 Bern, Switzerland. E-mail: msarneck@its.jnj.com.

© 2015 by Lippincott Williams & Wilkins, Inc.