Intradermal and intramuscular route for vaccination against hepatitis B M.L. Gonz~ilez *t, M. Usandizaga*, P. Alomar*, F. Saivh*, F. Martin*, M.J. Erroz* and R. Lardinois t A recombinant hepatitis B vaccine was administered to high-risk hospitalpersonnel by intramuscular (20 l~g) or intradermal (2 Itg) injections for the primary immunization (n=69) with three doses and booster immunization (n = 51) with one dose. Basic vaccination performed intramuscularly gave rise to significantly higher seroconversion levels (97.2% versus 78.1°/~) and geometric mean titres o f antibody (1649 versus 1261U1-1) as compared with the intradermal route. Intradermal administration did not boost antibody titres in patients previously vaccinated intradermally. Adverse reactions were not serious or severe. The intramuscular route is recommended as the procedure o f choice when vaccinating against hepatitis B. Keywords:Hepatitis B; recombinant vaccine; intramuscular; intradermal
Introduction In controlled studies carried out with three doses of hepatitis vaccine, no significant differences were established between the intramuscular (i.m.) and intradermal (i.d.) route in the incidence of local reactions, final seroconversion levels and anti-HBs titres I-4, although the latter were lower following i.d. administration. Since i.d. vaccination against hepatitis B may be performed with as low as one-tenth of the dose applied by the i.m. route, it should be possible to carry out large scale campaigns at low cost among high risk groups. The present study, performed with h!gh risk hospital personnel at Son Dureta Hospital, Palma de Mallorca, Spain, aimed at comparing, according to the route of administration, the immunogenicity and reactogenicity of a yeast recombinant hepatitis B vaccine, when performing primary and/or booster immunization.
Materials and methods This non-blind randomized controlled trial, carried out in parallel among high-risk susceptible hospital personnel s'6, started in March 1988 with the authorization of the Spanish Health Authorities. A group of 69 healthy personnel (36 women and 33 men) of 20 to 40 years of age with normal transaminase values and adequate weight for height (no more than 10% overweight) went through the primary vaccination, after consent was obtained before a witness. Pairs of men and women were constituted according to age (a difference of up to 1 year was allowed). Three doses of a recombinant hepatitis B vaccine from the same lot (Engerix-B, 130 A4, SK-RIT), were randomly administered to each vaccinee within a
pair at 0, 1 and 6 months, either i.m. (20 gg per dose) or i.d. (2/~g per dose). In December 1988, 51 staff members (22 women and 29 men) with antibody titres < 160 IU 1-1 were boosted with a fourth dose of the same batch of vaccine: 21 originated from the initial group of 69 participants, whereas 30 had been vaccinated, on a routine basis, one year before and exclusively by i.m. administration. Booster doses consisted of 2#g i.d., or 20#g i.m., and were randomly allocated within pairs of men or women, which were each homogeneous with respect to anti-HBs titres, age and weight. This procedure gave rise to four categories of subjects: those vaccinated and boosted by i.d. route (I) or by i.m. route (III), as well as those vaccinated by i.m. route and boosted by i.d. route (II) or vice versa (IV). Vaccinations in the left deltoid area were always performed by the same team of three nurses highly experienced in intramuscular and intradermal inoculations. Prior to vaccination as well as one month after the third and fourth dose, detection of HBsAg, anti-HBc and titration of anti-HBs were carried out by enzymoimmunoassay. Serum transaminase levels (normal values up to 50 IU 1-1) were determined by autoanalyser prior to and at the end of the trial. Mean values and percentages were statistically compared by means of the Student, Z2 and Fisher tests. Anti-HBs titres in each group were expressed in geometric means (GM) and were compared by the non-parametric Mann-Whitney test, attributing arbitrarily a value of 5 I U 1 - 1 to those sera in which antibody was not detectable.
Results *Hospital Son Dureta, Palma de Mallorca, Spain. tl.T.E.M.Pharma, Madrid, Spain. tCorrespondence should be addressed to: Maria Lourdes Gonz&lez Gonza.lez, Servicio de Obstetricia y Ginecologia, Hospital Son Dureta, C/ Andrea Doria, 55, 07014 Palma de Mallorca, Spain. (Received 25 September 1989; revised 22 February 1990; accepted 22 February 1990) 0264-410x/90/040402-04 © 1990 Butterworth-Heinemann Ltd
402 Vaccine, Vol. 8, August 1990
Following primary vaccination (Table I), i.m. administration (3 x 20 #g) induced significantly higher percentages of seroconversion ( > I O I U 1 - 1 ) as compared with i.d. regime (3 x 2 #g), both in the whole group of participants (97.2% versus 78.1%, p < 0.05) and in men (100% versus 64.3% , p
Introduction In controlled studies carried out with three doses of hepatitis vaccine, no significant differences were established between the intramuscular (i.m.) and intradermal (i.d.) route in the incidence of local reactions, final seroconversion levels and anti-HBs titres I-4, although the latter were lower following i.d. administration. Since i.d. vaccination against hepatitis B may be performed with as low as one-tenth of the dose applied by the i.m. route, it should be possible to carry out large scale campaigns at low cost among high risk groups. The present study, performed with h!gh risk hospital personnel at Son Dureta Hospital, Palma de Mallorca, Spain, aimed at comparing, according to the route of administration, the immunogenicity and reactogenicity of a yeast recombinant hepatitis B vaccine, when performing primary and/or booster immunization.
Materials and methods This non-blind randomized controlled trial, carried out in parallel among high-risk susceptible hospital personnel s'6, started in March 1988 with the authorization of the Spanish Health Authorities. A group of 69 healthy personnel (36 women and 33 men) of 20 to 40 years of age with normal transaminase values and adequate weight for height (no more than 10% overweight) went through the primary vaccination, after consent was obtained before a witness. Pairs of men and women were constituted according to age (a difference of up to 1 year was allowed). Three doses of a recombinant hepatitis B vaccine from the same lot (Engerix-B, 130 A4, SK-RIT), were randomly administered to each vaccinee within a
pair at 0, 1 and 6 months, either i.m. (20 gg per dose) or i.d. (2/~g per dose). In December 1988, 51 staff members (22 women and 29 men) with antibody titres < 160 IU 1-1 were boosted with a fourth dose of the same batch of vaccine: 21 originated from the initial group of 69 participants, whereas 30 had been vaccinated, on a routine basis, one year before and exclusively by i.m. administration. Booster doses consisted of 2#g i.d., or 20#g i.m., and were randomly allocated within pairs of men or women, which were each homogeneous with respect to anti-HBs titres, age and weight. This procedure gave rise to four categories of subjects: those vaccinated and boosted by i.d. route (I) or by i.m. route (III), as well as those vaccinated by i.m. route and boosted by i.d. route (II) or vice versa (IV). Vaccinations in the left deltoid area were always performed by the same team of three nurses highly experienced in intramuscular and intradermal inoculations. Prior to vaccination as well as one month after the third and fourth dose, detection of HBsAg, anti-HBc and titration of anti-HBs were carried out by enzymoimmunoassay. Serum transaminase levels (normal values up to 50 IU 1-1) were determined by autoanalyser prior to and at the end of the trial. Mean values and percentages were statistically compared by means of the Student, Z2 and Fisher tests. Anti-HBs titres in each group were expressed in geometric means (GM) and were compared by the non-parametric Mann-Whitney test, attributing arbitrarily a value of 5 I U 1 - 1 to those sera in which antibody was not detectable.
Results *Hospital Son Dureta, Palma de Mallorca, Spain. tl.T.E.M.Pharma, Madrid, Spain. tCorrespondence should be addressed to: Maria Lourdes Gonz&lez Gonza.lez, Servicio de Obstetricia y Ginecologia, Hospital Son Dureta, C/ Andrea Doria, 55, 07014 Palma de Mallorca, Spain. (Received 25 September 1989; revised 22 February 1990; accepted 22 February 1990) 0264-410x/90/040402-04 © 1990 Butterworth-Heinemann Ltd
402 Vaccine, Vol. 8, August 1990
Following primary vaccination (Table I), i.m. administration (3 x 20 #g) induced significantly higher percentages of seroconversion ( > I O I U 1 - 1 ) as compared with i.d. regime (3 x 2 #g), both in the whole group of participants (97.2% versus 78.1%, p < 0.05) and in men (100% versus 64.3% , p
