Short Poper Immunogenicity, reactogenicity and consistency of a new, inactivated hepatitis A vaccine- a randomized multicentre study with three consecutive vaccine lots B. Kallinowski*. K. Gmelin +, B. Kommerell*, H.L. Bock ~, R. Clemens**, N. Scheiermann ~, B. Wohland §, F. Hofmann °° and L. Theilmann*" We Owestigated immunogenicity, reactogenicity and cons&tency of three consecutive lots o f an inactivated hepatitis A vaccine in 204 seronegative volunteers. Each vohmteer received a total o f three doses o f vaccine (720 EIU) according to a O, 1 month primary vaccination schedule with a booster dose given at month 6. Mild, moderate and mostly local side effects were reported in 49.7% after the first and in less than 30% after the third injection. Seroconversion rate after one vaccine dose was as high as 91%. All subjects but one had already seroconverted by 1 month after the second injection, corresponding to a seroconversion rate of 99%. The geometric mean titres ( GMT) increased with each dose o f vaccine administered. Our results show that this inactivated hepatitis A vaccine is highly immunogenic, safe and well tolerated. Furthermore, there were no significant differences between the three vaccine lots in respect to seroconversion rate, size of antibody titre or reactogenicity. Keywords: Hepatitis A vaccination; consistency; immunogenicity; safety

The prevalence of HAV infection in western Europe has decreased during the last two decades due to high standards of hygiene 1-~. Therefore tourists to countries with endemic hepatitis A virus infection run a high risk of acquiring this disease, which often becomes symptomatic in adult patients. Until now, only immunoglobulin preparations containing neutralizing antibodies to hepatitis A virus (anti-HAV) were available for travellers for immunoprophylaxis of hepatitis A virus infection. Owing to the half-life of immunoglobulins only a temporary and not completely reliable protection against HAV infection could be achieved. However, recently active vaccination has become available for the first time 5'6. In this study we investigated the immunogenicity, reactogenicity and consistency of a new, inactivated hepatitis A vaccine. *University Hospital of Heidelberg, Department of Internal Medicine IV, University of Heidelberg, Bergheimer Str. 58, D 6900 Heidelberg, Germany. ~Luitpold Hospital, Bad Kiissingen, Germany. :SmithKline Beecham Pharma, Munich, Germany. §St Markus Hospital, Frankfurt, Germany. =Universit&tsklinik Freiburg, Freiburg, Germany. rTo whom correspondence should be addressed. (Received 27 November 1991; accepted 3 February 1992) 0264-410)(,92080500-02 C~ 1992 Butterworth-Heinemann Ltd

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The inactivated hepatitis A vaccine (SmithKline Biologicals, Rixensart, Belgium ) is derived from the HM 175 strain, containing 720 EIU of HAV adsorbed to 0.5 mg AI(OH) s in a total volume of 1 ml. The study was performed after being approved by the ethical review committee of the University of Heidelberg. Included in the study were anti-HAV-negative volunteers aged 18-40 years. Excluded from study entry were anti-HAV-positive individuals, persons with malignant or chronic diseases or with permanent drug or alcohol abuse, pregnant women, and persons with elevated liver function tests. The three doses of vaccine were administered at 0, 1 and 6 months. Liver function tests and titration of anti-HAV antibodies were done at month 0, 1, 2, 6 and 7. Side effects were documented by symptom sheets to be filled out by each vaccinee for three consecutive days after each vaccination. GGT, ALT and AST were measured by an automatic enzyme assay (Hitachi Test, Boehringer Mannheim). The normal range for GGT was 0.5

within one group, we used the X2 t e s t and the Fisher's exact test. A total of 213 healthy volunteers were recruited at five different centres and randomized to three different groups according to the three different vaccine lots. Nine subjects had to be withdrawn from the immunogenicity and consistency analysis due to protocol violations but were included in the safety follow-up. The ratio of men:women was 1:1.04, and the mean age 27.2 years. Age and sex distribution in each group were not significantly different. The incidence of local (soreness, redness, swelling, induration) and systemic (headache, nausea, loss of appetite, vomiting) side effects was highest after the first injection with an overall incidence of 49.7% and decreased significantly to less than 30% after the second and third booster injection. No significant differences among the three different vaccine lots were noted with respect to quality and quantity of the side effects (Figure l ). The most common local complaint was pain at the injection site with an incidence of 24.8% (153/628) of all doses. Headache was the most common general symptom with an overall incidence of 6.6%. All side effects disappeared spontaneously within 3 days and were classified as mild or moderate. All 204 evaluable volunteers were

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Steffen, R. Reisemedizin. Springer, Heidelberg, 1984. 90-96 Szmuness, W., Dienstag, J., Purcell, R.H., Stevens, C., Wong, D.C., Ikram, H., Bar-Shany, Sh. et al. The prevalence of antibody to hepatitis A antigen in various parts of the world: a pilot study. Am. J. Epidemiol. 1977, 106, 392-398 Wiedermann, G., Ambrosch, F., Kollaritsch, H., Hofmann, H., Kunz, C., D'Hondt, E.D. et al. Safety and immunogenicity of an inactivated hapatitis A candidate vaccine in healthy adult volunteers. Vaccine 1990, 8, 581-584 Flehmig, B., Heinrich, U. and Pfisterer, M Immunogenicity of a killed hepatitis A vaccine in seronegative volunteers. Lancet 1989, i, 1039-1041 M011er,R.. Chriske, H.. Deinhardt, F., Jilg, W., Gmelin. K., Theilmann, L, Hess, G. et al. Aktive Hepatitis A Immunisierung: Immunogenit~t und Vertr&glichkeit verschiedener Impfschemata. Z. Gastroenterol. 1990, 28, 712 (abstract) Andre, F., Hepburn, A. and D'Hondt, E. Inactivated candidate vaccines for hepatitis A. Prog. Med. Virol. 1990, 37, 72-95 Ambrosch, F., Wiedermann, G., Andre, F.E., D'Hondt, E., Delem, A. and Safary, A. Comparison of HAV antibodies induced by vaccination, passive immunization and natural infection. Proc. 1990 International Symposium on Viral Hepatitis and Liver Disease, 4-8 April 1990, Houston, USA (abstract) Eyelenbosch, W., Safary, A., Moonsammy, G., Boscia, J. and Andre, F. Comparative anti-HAV responses in healthy adults following passive or active immunization. Proc. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, 21-24 October 1990, Atlanta, USA (abstract)

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Immunogenicity, reactogenicity and consistency of a new, inactivated hepatitis A vaccine--a randomized multicentre study with three consecutive vaccine lots.

We investigated immunogenicity, reactogenicity and consistency of three consecutive lots of an inactivated hepatitis A vaccine in 204 seronegative vol...
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