A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine

A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.     

Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine

A Phase I trial was performed to investigate the safety and immunogenicity of the third generation smallpox vaccine MVA-BN (IMVAMUNE), a highly attenuated clone derived from the Modified Vaccinia Virus Ankara strain 571, in naive and pre-immunized subjects. A total of 86 healthy subjects received the vaccine in five groups using different doses and routes of administration. All 38 subjects seroconverted in the groups receiving the highest dose (10(8) TCID50). All vaccinations were well tolerated with mainly mild or moderate pain at the injection site being the most frequent symptom. The results indicate that MVA-BN has the potential to be developed as an efficient and safe alternative to the conventional smallpox vaccines such as Lister-Elstree or Dryvax. Unique attributes render it a promising candidate for prophylactic mass immunization, even in subjects for whom conventional smallpox vaccines are contraindicated.     

Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late

BACKGROUND: An influx of immunocytes, increased epidermal proliferation and abnormal keratinization are hallmarks of the psoriatic lesion. T-lymphocyte subsets in particular activated effector memory T cells and natural killer (NK) T cells have been suggested to play an important role in the pathogenesis of psoriasis. OBJECTIVES: In the present study we investigated the number of T-cell subsets (CD4, CD8, CD45RO, CD45RA, CD2, CD25), cells expressing NK receptors (CD94 and CD161), the proliferation marker Ki67 and the keratinization marker keratin (K10) across the margin of the spreading psoriatic plaque: distant uninvolved skin, the outer margin (immediately outside the clinical edge), the inner margin (immediately inside the clinical edge) and the central area. PATIENTS AND METHODS: Eight patients with active psoriasis vulgaris participated in this study. Biopsies were taken from the spreading psoriatic lesion from the distant uninvolved skin, the outer margin, the inner margin and the central area. Biopsies were processed for immunohistochemical staining. RESULTS: In the outer margin CD8+ (cytotoxic T cells) and CD45RO+ (memory effector T cells) T lymphocytes invade the epidermis and in this early stage the activation markers CD2 and CD25 also show a substantial increase. The next phase, from the outer to the inner margin, shows a statistically significant increase of these markers, and especially, the cells expressing NK receptors (CD94 and CD161) show a massive increase together with a significant increase of epidermal proliferation (Ki67) and a decrease of the K10+ epidermal surface. CONCLUSIONS: CD8+, CD45RO+, CD2+ and CD25+ T cells have a role in the early phase of the psoriatic process, whereas CD94- and CD161-expressing cells together with epidermal proliferation and keratinization are involved in a later phase.     

Comparison of thiomersal-free and thiomersal-containing formulations of a recombinant hepatitis B vaccine (Hepavax-Gene) in healthy adults

A thiomersal-free (TF) formulation of the recombinant hepatitis B vaccine Hepavax-Gene has been developed. This study compared immunogenicity and safety of Hepavax-Gene, Hepavax-Gene TF and Engerix-B (containing trace amounts of thiomersal) in a large healthy adult population (N=770) using two vaccination schedules: the priming 0-1-2 months or the standard 0-1-6 month schedule. Hepavax-Gene TF was non-inferior to Hepavax-Gene and Engerix-B with respect to seroprotection rates (>or=10I U/L) 1 month after the third vaccination using the 0-1-6 month schedule, with 99.1% for both Hepavax-Gene formulations and 100% for Engerix-B of subjects' seroprotected in each group. The seroprotection rate after the 0-1-2 schedule was 89.6% for Hepavax-Gene TF, lower than for Hepavax-Gene (94.2%) but comparable to Engerix-B (86.4%). Furthermore, Hepavax-Gene TF was as well tolerated as the comparator vaccines.