Safety and immunogenicity of two Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given with diphtheria-tetanus-pertussis vaccine to young Papua New Guinean children.

BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit. METHODS: We evaluated the safety and immunogenicity of a lyophilized and a liquid form of Hib polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given in the same syringe as diphtheria-tetanus-pertussis (DTP) vaccine to children in Goroka, Eastern Highlands Province. In Part 1 of the study 209 children were randomized to receive at ages 1, 2 and 3 months either DTP alone or a liquid formulation of DTP/PRP-T or lyophilized PRP-T dissolved in DTP suspension. A further 75 children were given the liquid DTP/PRP-T formulation at ages 2, 3 and 4 months (Part 2). 54 children aged 15-18 months were given a booster of the same preparation of PRP-T/DTP as they had received during Part 1. Blood for antibody assays was collected at enrolment, before (Part 1 only) and one month after the third dose, then just before and 3 weeks after the booster dose. RESULTS: Follow-up to age of 12 months showed that PRP-T was safe with no evidence of impaired response to individual vaccine components when combined with DTP. Geometric mean titres (GMTs) of anti-PRP antibody before vaccination (n = 64, mean age 41 days), after 2 doses (mean age 99 days) and after 3 doses (mean age 132 days) of the lyophilized formulation were 0.21, 1.48 and 5.04 microg/ml, respectively, with 58% and 89% having anti-PRP antibody titres > or = 1.0 microg/ml after 2 and 3 doses, respectively. Anti-PRP antibody responses to the liquid Hib vaccine formulation were lower (GMT post-dose 3 = 0.48 microg/ml) than to the lyophilized formulation, but better responses were elicited from older children (Part 2; GMT post-dose 3 = 0.78 microg/ml, with 79% > or = 0.15 microg/ml). Both PRP-T preparations elicited excellent booster responses suggesting that children are likely to be protected if exposed to Hib infection. CONCLUSIONS: Lyophilized PRP-T given together with DTP is safe and immunogenic when given to young infants. The liquid DTP/PRP-T formulation showed a lower immunogenicity than in earlier studies with this vaccine, which might have been due to exposure to low temperature during shipment or the younger age at immunization.

Comparison of immunogenicity and safety of a virosome influenza vaccine with those of a subunit influenza vaccine in pediatric patients with cystic fibrosis.

The objective of this study was to compare the immunogenicity and safety of a single-dose regimen and a two-dose regimen of a trivalent virosome influenza vaccine (Inflexal Berna V) with those of a trivalent subunit influenza vaccine (Influvac) in children and adolescents with cystic fibrosis (CF). In an open, randomized, multicenter study with parallel groups, 11 young children with CF (1 to 6 years old) and 53 older children and adolescents with CF (>6 years old) were randomly assigned to one of the following immunization regimens: virosome vaccine at 0.5 ml on study day 0 or 0.25 ml on days 0 and 28 or a standard regimen of subunit vaccine, i. e., 0.5 ml on day 0 for older children and 0.25 ml on days 0 and 28 for younger children. Safety assessments, i.e., recording of systemic and local adverse events (AEs) and vital signs, were made for a 5-day observation period after each immunization. Hemagglutination inhibition (HI) titers were determined at baseline and 4 weeks after the single-dose and the two-dose immunizations, respectively. Immunogenicity was assessed according to the criteria of the European Agency for the Evaluation of Medicinal Products (EMEA). Both vaccines induced comparable HI antibody titers. Seroconversion (> or =4-fold rise in HI antibody titers, reaching a titer of > or =1:40) was achieved in 41 to 100% of the participants. Seroprotection (HI titer, > or =1:40) and a >2.5-fold increase in geometric mean titers were achieved in 100% of the participants. Thus, all three EMEA requirements for influenza vaccine efficacy were met by all treatment groups and for both vaccines. The virosome vaccine, when administered as a single dose, seemed to induce superior immunogenicity compared with the standard pediatric two-dose regimen. Totals of 42 and 57% of vaccinees receiving virosome and subunit vaccines, respectively, reported at least one local AE (predominantly pain). Totals of 84 and 71% of subjects receiving virosome and subunit vaccines, respectively, complained in response to questions of at least one systemic AE (mainly cough, fatigue, coryza, or headache). The majority of events were mild or moderate and lasted 1 or 2 days only. No obvious relationship was found between AE reporting rate and vaccine formulation, age group, or dose regimen. The relatively high AE reporting rate seemed to be partly related to the symptomatology of the underlying CF disease. In summary, the virosome and subunit vaccines induced in both age groups and against all three influenza strains an efficient immune response and were well tolerated by the children and adolescents with CF.

[Immunogenicity and stability of an aluminum-free liposomal hepatitis A vaccine (Epaxal Berna)]. / Immunogenität und Stabilität eines aluminiumfreien liposomalen Hepatitis-A-Impfstoffs (Epaxal Berna).

The high immunogenicity of the liposomal hepatitis A vaccine (Epaxal Berna) after a single dose and after a booster dose one year later has been confirmed in several studies with healthy adult volunteers: 95-100% and 96-100% seroconversion (> or = 20 mIE/ml) after 1 and 12 months respectively, as well as a booster effect in 100% of the cases after revaccination. The tolerability of this new, alum-free vaccine has been excellent with 6-25% local and 0-13% mild systemic reactions after a dose of 0.5 ml. Stability testing with and without detergent indicated partial internalization of the hepatitis A virions in the phospholipid bilayer of the liposome vesicles with storage. Immunization of 10 healthy adult volunteers with vaccine stored for 32 months at 4 degrees C showed, however, that the duration of storage has no influence on immunogenicity and tolerability of the vaccine.