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Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines
Vaccine 20 (2002) 292–293
Letter to the Editor
Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines F.E. Andre∗ GlaxoSmithKline Biologicals, Rue de l’Institut 89, 1330 Rixensart, Belgium Accepted 14 August 2001
I would like to respond to the recent publication of Bryan et al. [1] on a cross-over, randomized, comparison of two inactivated hepatitis A vaccines. In the study the authors compare four groups receiving either Havrix/Havrix, Vaqta/Vaqta, Havrix/Vaqta, Vaqta/Havrix. Both vaccines are licensed for a two-dose (0, 6–12 months) schedule. They are well tolerated and highly immunogenic [2,3] which was confirmed in the study. The investigators discuss the fact that the 32% seroconversion rate they observed 15 days after the first dose of Havrix is not in line with the FDA-approved Prescribing Information for Havrix which states that by day 15, 80–98% of vaccines have seroconverted (anti-HAV ≥ 20 mIU/ml) [4]. This finding is of particular importance because the results reported by Bryan et al. may cause concern in people seeking rapid protection against hepatitis A by active immunization and who are often given only the first dose of the hepatitis A vaccine prior to departure. The results reported by Bryan et al. are indeed not in line with this claim. Actually, the seroconversion rate at day 15, stated in the Prescribing Information for Havrix, is based on several independent clinical studies conducted in different age groups. A first study by Van Damme et al. [5] conducted in 444 adults, aged 18–62 years, showed that 88.1% of the vaccinees had acquired antibodies against hepatitis A by day 15. Another study [6] in 151 adults, aged 18–40 years, showed that 96% had seroconverted. And a third study [7] in 113 adults, aged between 20–39 years, showed that 90% had antibodies against hepatitis A, 2 weeks after receiving the first dose. The latter study also included a group of 66 older subjects (between 40–62 years) of whom 77% had antibodies 2 weeks after the first dose [7]. Additionally, Bryan et al. omit to mention that the 43% (41/96) recipients of ∗ Tel.: +32-2-656-83-35; fax: +32-2-656-90-58. E-mail address: [email protected] (F.E. Andre).
0264-410X/01/$ – see front matter © 2001 Published by Elsevier Science Ltd. PII: S 0 2 6 4 - 4 1 0 X ( 0 1 ) 0 0 3 6 9 - 3
Vaqta who developed antibodies against hepatitis A 2 weeks after the first dose, is also lower than the 69% mentioned in the Prescribing Information for Vaqta [8]. It thus appears that the immune response after the first doses, irrespective of the vaccine administered, is lower in this study than that reported elsewhere. Although, the authors offer no explanation for this finding, possible reasons might be differences in antibody titration techniques, enrolment of subjects whose mean age is >30 years, with a high proportion of males or other unidentified factors. It is important to remember that both Havrix and Vaqta are licensed on a two-dose schedule. Therefore, one has also to consider the results obtained after the full vaccination course. All vaccinees, irrespective of the vaccine combinations received, developed antibodies against hepatitis A with high concentrations in all study groups. These results would thus concur with the view of the CDC that the two vaccines can be considered interchangeable [9]. Bryan et al. are indeed right when they mention that, cases of acute hepatitis A shortly after vaccination are extremely rare. This could well indicate that a hepatitis A vaccine can be effective even when given shortly before travel to an endemic area, because the onset of protection after hepatitis A vaccination (first dose) may be rapid. Actually, hepatitis A vaccines have successfully been used to control large scale outbreaks of hepatitis A, for example, in Alaska [10] and also in numerous other settings. The inactivated hepatitis A vaccine (Havrix) has also been shown efficacious in pre- and post-exposure studies not only in marmosets [11], but also in a household setting [12]. In conclusion, from a public health perspective, there is sufficient scientific and medical evidence that demonstrates that current inactivated hepatitis A vaccines are well tolerated and efficacious in preventing hepatitis A, and that, contrary to the suggestion of Bryan et al., they are interchangeable.
F.E. Andre / Vaccine 20 (2002) 292–293
Havrix is a trademark of SmithKline Beecham Biologicals, Rixensart, Belgium and Vaqta is a trademark of Merck and Co., West Point, PA. References [1] Bryan JP, Henry CH, Hoffman AG, et al. Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. Vaccine 2000;19:743–50. [2] Nalin D, Kuter B, Brown L, et al. Worldwide experience with the CR3 26F-derived inactivated hepatitis A virus vaccine in pediatric and adult populations: an overview. J Hepatol 1993;18 (Suppl 2):S51–5. [3] Clemens R, Safary A, Hepburn A, Roche C, Stanbury W, Andre F. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995;171(Suppl 1):S44–9. [4] Havrix US Prescribing Information, SmithKline Beecham Biologicals. [5] Van Damme P, Mathei C, Thoelen S, Meheus A, Safary A, Andre FE. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol 1994;44:435–41.
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[6] Victor J, Dahl Knudsen J, Nielsen LP, et al. Hepatitis A vaccine. A new convenient single dose schedule with booster when long-term immunisation is warranted. Vaccine 1994;12:1327–9. [7] Briem H, Safary A. Immunogenicity and safety in adults of hepatitis A virus vaccine administered as a single dose with a booster 6 months later. J Med Virol 1994;44:443–5. [8] HYPERLINK http://www.vaccinesbynet.com/vaccines/ (Merck Vaccine information). [9] Anonymous. Prevention of hepatitis A through active or passive immunization. Morbidity and Mortality Weekly Review 1999;48: NoRR-12:1–37. [10] McMahon BJ, Beller M, Williams J, Schloss M, Tanttila H, Bulkow L. A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med 1996;150:733–9. [11] D’Hondt E, Purcell RH, Emerson SU, Wong DC, Shapiro M, Govindarajan S. Efficacy of an inactivated hepatitis A vaccine in preand post-exposure conditions in marmosets. J Inf Dis 1995;171(Suppl 1):S40–3. [12] Sagliocca L, Amoroso P, Stroffolini T, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. Lancet 1999;353(9159):1136-9.
Letter to the Editor
Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines F.E. Andre∗ GlaxoSmithKline Biologicals, Rue de l’Institut 89, 1330 Rixensart, Belgium Accepted 14 August 2001
I would like to respond to the recent publication of Bryan et al. [1] on a cross-over, randomized, comparison of two inactivated hepatitis A vaccines. In the study the authors compare four groups receiving either Havrix/Havrix, Vaqta/Vaqta, Havrix/Vaqta, Vaqta/Havrix. Both vaccines are licensed for a two-dose (0, 6–12 months) schedule. They are well tolerated and highly immunogenic [2,3] which was confirmed in the study. The investigators discuss the fact that the 32% seroconversion rate they observed 15 days after the first dose of Havrix is not in line with the FDA-approved Prescribing Information for Havrix which states that by day 15, 80–98% of vaccines have seroconverted (anti-HAV ≥ 20 mIU/ml) [4]. This finding is of particular importance because the results reported by Bryan et al. may cause concern in people seeking rapid protection against hepatitis A by active immunization and who are often given only the first dose of the hepatitis A vaccine prior to departure. The results reported by Bryan et al. are indeed not in line with this claim. Actually, the seroconversion rate at day 15, stated in the Prescribing Information for Havrix, is based on several independent clinical studies conducted in different age groups. A first study by Van Damme et al. [5] conducted in 444 adults, aged 18–62 years, showed that 88.1% of the vaccinees had acquired antibodies against hepatitis A by day 15. Another study [6] in 151 adults, aged 18–40 years, showed that 96% had seroconverted. And a third study [7] in 113 adults, aged between 20–39 years, showed that 90% had antibodies against hepatitis A, 2 weeks after receiving the first dose. The latter study also included a group of 66 older subjects (between 40–62 years) of whom 77% had antibodies 2 weeks after the first dose [7]. Additionally, Bryan et al. omit to mention that the 43% (41/96) recipients of ∗ Tel.: +32-2-656-83-35; fax: +32-2-656-90-58. E-mail address: [email protected] (F.E. Andre).
0264-410X/01/$ – see front matter © 2001 Published by Elsevier Science Ltd. PII: S 0 2 6 4 - 4 1 0 X ( 0 1 ) 0 0 3 6 9 - 3
Vaqta who developed antibodies against hepatitis A 2 weeks after the first dose, is also lower than the 69% mentioned in the Prescribing Information for Vaqta [8]. It thus appears that the immune response after the first doses, irrespective of the vaccine administered, is lower in this study than that reported elsewhere. Although, the authors offer no explanation for this finding, possible reasons might be differences in antibody titration techniques, enrolment of subjects whose mean age is >30 years, with a high proportion of males or other unidentified factors. It is important to remember that both Havrix and Vaqta are licensed on a two-dose schedule. Therefore, one has also to consider the results obtained after the full vaccination course. All vaccinees, irrespective of the vaccine combinations received, developed antibodies against hepatitis A with high concentrations in all study groups. These results would thus concur with the view of the CDC that the two vaccines can be considered interchangeable [9]. Bryan et al. are indeed right when they mention that, cases of acute hepatitis A shortly after vaccination are extremely rare. This could well indicate that a hepatitis A vaccine can be effective even when given shortly before travel to an endemic area, because the onset of protection after hepatitis A vaccination (first dose) may be rapid. Actually, hepatitis A vaccines have successfully been used to control large scale outbreaks of hepatitis A, for example, in Alaska [10] and also in numerous other settings. The inactivated hepatitis A vaccine (Havrix) has also been shown efficacious in pre- and post-exposure studies not only in marmosets [11], but also in a household setting [12]. In conclusion, from a public health perspective, there is sufficient scientific and medical evidence that demonstrates that current inactivated hepatitis A vaccines are well tolerated and efficacious in preventing hepatitis A, and that, contrary to the suggestion of Bryan et al., they are interchangeable.
F.E. Andre / Vaccine 20 (2002) 292–293
Havrix is a trademark of SmithKline Beecham Biologicals, Rixensart, Belgium and Vaqta is a trademark of Merck and Co., West Point, PA. References [1] Bryan JP, Henry CH, Hoffman AG, et al. Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. Vaccine 2000;19:743–50. [2] Nalin D, Kuter B, Brown L, et al. Worldwide experience with the CR3 26F-derived inactivated hepatitis A virus vaccine in pediatric and adult populations: an overview. J Hepatol 1993;18 (Suppl 2):S51–5. [3] Clemens R, Safary A, Hepburn A, Roche C, Stanbury W, Andre F. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995;171(Suppl 1):S44–9. [4] Havrix US Prescribing Information, SmithKline Beecham Biologicals. [5] Van Damme P, Mathei C, Thoelen S, Meheus A, Safary A, Andre FE. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol 1994;44:435–41.
293
[6] Victor J, Dahl Knudsen J, Nielsen LP, et al. Hepatitis A vaccine. A new convenient single dose schedule with booster when long-term immunisation is warranted. Vaccine 1994;12:1327–9. [7] Briem H, Safary A. Immunogenicity and safety in adults of hepatitis A virus vaccine administered as a single dose with a booster 6 months later. J Med Virol 1994;44:443–5. [8] HYPERLINK http://www.vaccinesbynet.com/vaccines/ (Merck Vaccine information). [9] Anonymous. Prevention of hepatitis A through active or passive immunization. Morbidity and Mortality Weekly Review 1999;48: NoRR-12:1–37. [10] McMahon BJ, Beller M, Williams J, Schloss M, Tanttila H, Bulkow L. A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med 1996;150:733–9. [11] D’Hondt E, Purcell RH, Emerson SU, Wong DC, Shapiro M, Govindarajan S. Efficacy of an inactivated hepatitis A vaccine in preand post-exposure conditions in marmosets. J Inf Dis 1995;171(Suppl 1):S40–3. [12] Sagliocca L, Amoroso P, Stroffolini T, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial. Lancet 1999;353(9159):1136-9.