Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents

Seo Hee Yoon, Han Wool Kim, Jong Gyun Ahn, In Tae Kim, Jong-Hyun Kim, Kyoung Ae Kong, Kyung-Hyo Kim, Seo Hee Yoon, Han Wool Kim, Jong Gyun Ahn, In Tae Kim, Jong-Hyun Kim, Kyoung Ae Kong, Kyung-Hyo Kim

Abstract

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim™, Epaxal®, or Havrix®, 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim™, Epaxal®, and Havrix®, respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim™, Epaxal®, and Havrix® respectively. Avaxim™ was significantly more immunogenic than Epaxal® and Havrix®, whereas there were no significant differences in antibody responses between Epaxal® and Havrix®. Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470).

Keywords: Adolescent; Antibody Formation; Hepatitis A Vaccines; Safety.

Conflict of interest statement

DISCLOSURE: The authors have no conflicts of interest to disclose regarding this study.

Figures

Fig. 1. Study design and disposition of…
Fig. 1. Study design and disposition of subjects. *Subjects were excluded due to ineligibility for the study. ITT, intention-to-treat; PP, per-protocol; P, pediatric dose; A, adult dose.
Fig. 2. Comparison of the immunogenicity of…
Fig. 2. Comparison of the immunogenicity of the three hepatitis A vaccines at each visit. (A) Comparison among the Vaccine A, Vaccine B, and Vaccine C groups. (B) Comparison among the subgroups with three pediatric doses of each vaccine. (C) Comparison between the subgroups with two adult doses of each vaccine. Visit 1, at enrollment; visit 2, one month after the first dose; visit 3, just prior to the second dose (6 to 12 months after the first dose); visit 4, one month following the second dose.
Fig. 3. Reverse cumulative distribution curves of…
Fig. 3. Reverse cumulative distribution curves of the anti-HAV antibody concentrations for the three vaccine groups at each visit. Vertical solid line, cut-off value for anti-HAV seroprotection, 20 mIU/mL.

References

    1. Franco E, Bagnato B, Marino MG, Meleleo C, Serino L, Zaratti L. Hepatitis B: Epidemiology and prevention in developing countries. World J Hepatol. 2012;4:74.
    1. WHO. WHO position paper on hepatitis A vaccines – June 2012. Wkly Epidemiol Rec. 2012;87:261–276.
    1. Kim JH. Recent epidemiological status and vaccination of hepatitis A in Korea. J Korean Med Assoc. 2008;51:110–118.
    1. Li RC, Li Y, Yi N, Huang L, Wan Z, Zhang Y, Rasuli A. An open, prospective, randomized study comparing the immunogenicity and safety of two inactivated hepatitis A pediatric vaccines in toddlers, children and adolescents in China. Pediatr Infect Dis J. 2013;32:e77–e81.
    1. American Academy of Pediatrics Committee on Infectious Diseases. Hepatitis A vaccine recommendations. Pediatrics. 2007;120:189–199.
    1. Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010;28:6653–6657.
    1. Lee H, Cho HK, Kim JH, Kim KH. Seroepidemiology of hepatitis A in Korea: changes over the past 30 years. J Korean Med Sci. 2011;26:791–796.
    1. Kim YJ, Lee HS. Increasing incidence of hepatitis A in Korean adults. Intervirology. 2010;53:10–14.
    1. Jeong SH. Current status and vaccine indication for hepatitis A virus infection in Korea. Korean J Gastroenterol. 2008;51:331–337.
    1. Key H. World's first hepatitis A vaccine. Inpharma Wkly. 1992;823:14–15.
    1. Murphy TV, Feinstone SM. Hepatitis A vaccines. In: Plotkin SA, editor. Vaccines. Philadelphia, PA: Saunders Elsevier; 2013. pp. 183–204.
    1. Fiore AE, Wasley A, Bell BP Advisory Committee on Immunization Practices (ACIP) Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep. 2006;55(RR-7):1–23.
    1. Fangcheng Z, Xuanyi W, Mingding C, Liming J, Jie W, Qi J, Yuanping G, Wen Q, Yajuan X, Jiangsen M. Era of vaccination heralds a decline in incidence of hepatitis A in high-risk groups in China. Hepat Mon. 2012;12:100–105.
    1. Vidor E, Dumas R, Porteret V, Bailleux F, Veitch K. Aventis Pasteur vaccines containing inactivated hepatitis A virus: a compilation of immunogenicity data. Eur J Clin Microbiol Infect Dis. 2004;23:300–309.
    1. Bovier PA. Epaxal: a virosomal vaccine to prevent hepatitis A infection. Expert Rev Vaccines. 2008;7:1141–1150.
    1. Abarca K, Ibáñez I, de la Fuente P, Cerda L, Bergeret J, Frösner G, Ibarra H. Immunogenicity and tolerability of a paediatric presentation of a virosomal hepatitis A vaccine in Chilean children aged 1-16 years. Vaccine. 2011;29:8855–8862.
    1. Bovier PA, Bock J, Ebengo TF, Frösner G, Glaus J, Herzog C, Loutan L. Predicted 30-year protection after vaccination with an aluminum-free virosomal hepatitis A vaccine. J Med Virol. 2010;82:1629–1634.
    1. 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;12:270–277.
    1. Soysal A, Gokçe I, Pehlivan T, Bakir M. Interchangeability of a hepatitis A vaccine second dose: Avaxim 80 following a first dose of Vaqta 25 or Havrix 720 in children in Turkey. Eur J Pediatr. 2007;166:533–539.
    1. López EL, Contrini MM, Xifró MC, Cattaneo MA, Zambrano B, Dumas R, Rouyrre N, Weber F. Hepatitis A vaccination of Argentinean infants: comparison of two vaccination schedules. Vaccine. 2007;25:102–108.
    1. Lim J, Song YJ, Park WS, Sohn H, Lee MS, Shin DH, Kim CB, Kim H, Oh GJ, Ki M. The immunogenicity of a single dose of hepatitis A virus vaccines (Havrix® and Epaxal®) in Korean young adults. Yonsei Med J. 2014;55:126–131.
    1. Zuckerman JN, Kirkpatrick CT, Huang M. Immunogenicity and reactogenicity of Avaxim (160 AU) as compared with Havrix (1440 EL.U) as a booster following primary immunization with Havrix (1440 EL.U) against hepatitis A. J Travel Med. 1998;5:18–22.
    1. Orr N, Klement E, Gillis D, Sela T, Kayouf R, Derazne E, Grotto I, Balicer R, Huerta M, Aviram L, et al. Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines. Vaccine. 2006;24:4328–4332.
    1. Van Der Wielen M, Vertruyen A, Froesner G, Ibáñez R, Hunt M, Herzog C, Van Damme P. Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years. Pediatr Infect Dis J. 2007;26:705–710.
    1. Dagan R, Amir J, Livni G, Greenberg D, Abu-Abed J, Guy L, Ashkenazi S, Foresner G, Tewald F, Schätzl HM, et al. Concomitant administration of a virosome-adjuvanted hepatitis A vaccine with routine childhood vaccines at age twelve to fifteen months: a randomized controlled trial. Pediatr Infect Dis J. 2007;26:787–793.

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