Interchangeability of two diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccines as a fourth dose in 15-20-month-old toddlers.

BACKGROUND: Since 1998, all children in Canada have been immunized with a pentavalent diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib) produced by one manufacturer (Pentacel). Recently, another DTaP-IPV-Hib (Infanrix-IPV-Hib) became available. Data on the interchangeability of these products was lacking. METHODS: In this multicentered, observer-blind study, healthy 15-20-month-old children previously immunized with three doses of Pentacel were randomly allocated to receive a single dose of Pentacel or Infanrix-IPV-Hib. Adverse events were documented by diary for 7 days post-immunization and unsolicited adverse events were documented for 30 days. RESULTS: 433 participants were enrolled (mean age 17.1 months). Rates of fever, anorexia and irritability were similar in both groups. Injection-site redness >20 mm (11.5% versus 5.6%; p = 0.038), injection-site pain (52.1% versus 39.4%; p = 0.009) and moderate or greater drowsiness (13.8% versus 7.4%; p = 0.042) were more common after Pentacel than Infanrix-IPV-Hib. The proportions of participants who were sero-protected or who sero-responded were similar for all antigens. Geometric mean titers or concentrations were similar for antibodies against diphtheria toxoid and poliovirus type 3. Geometric mean concentrations or titers were higher in the Infanrix-IPV-Hib group against pertussis toxin (88.5 EU/mL versus 65.6 EU/mL), filamentous hemagglutinin (207.3 EU/mL versus 132.1 EU/mL), pertactin (251.9 EU/mL versus 166.9 EU/mL) and poliovirus type 1 (1293.7 versus 976.2 reciprocal dilution). Geometric mean titers or concentrations were higher in the Pentacel group against H. influenzae type b (29 microg/mL versus 19 microg/mL), tetanus toxoid (5.6 IU/mL versus 4.7 IU/mL) and poliovirus type 2 (1437.3 versus 1134.2 reciprocal dilution). CONCLUSIONS: A booster dose of Infanrix-IPV-Hib after three priming doses of Pentacel is well-tolerated and immunogenic in 15-20-month-old toddlers and can be used interchangeably.

Canadian Association for Immunization Research and Evaluation (CAIRE) guidelines for industry-sponsored clinical trial and epidemiology contract research.

In response to concerns about interactions of academic and public health investigators with industry, the Canadian Association for Immunization Research and Evaluation (CAIRE), in collaboration with six major vaccine manufacturers, developed guidelines for participation in industry-sponsored clinical trial and epidemiology contract research within Canada. Topics addressed include definition of investigators, data ownership, protocol development, data management, data analysis, producing a study report and publication of the results of the study.

Promiscuous and reversible blocker of presynaptic calcium channels in frog and crayfish neuromuscular junctions from Phoneutria nigriventer spider venom.

Peptide channel blockers found in venoms of many predators are useful pharmacological tools and potential therapeutic agents. The venom of the Brazilian spider Phoneutria nigriventer contains a fraction, omega-phonetoxin-IIA (omega-Ptx-IIA, 8360 MW), which blocks Ca2+ channels. At frog neuromuscular junctions (NMJ) bathed in normal Ca2+ (1.8 mM) saline, omega-Ptx IIA did not affect spontaneous transmitter release but reversibly reduced evoked transmitter release by 75 and 95% at 12 and 24 nM, respectively. In contrast, toxin effects were irreversible in low-Ca2+ (0.5 mM) saline. Ca2+ imaging in normal-Ca2+ saline showed that omega-Ptx-IIA partially blocked stimulus-dependent presynaptic Ca2+ signals, and the blockade was almost completely reversible. Increases in spontaneous release frequency induced by high extracellular K+ were blocked by omega-Ptx-IIA. Therefore omega-Ptx-IIA blocks N-type Ca2+ channels, which admit Ca2+ that triggers transmitter release at the frog NMJ. Additional evidence predicts that omega-Ptx-IIA binds to N-type Ca2+ channels at a different site from that of omega-Conotoxin-GVIA. omega-Ptx-IIA also gave a low-affinity partial blockade of transmitter release and presynaptic Ca2+ signals at crayfish NMJs where P-type channels are blocked by omega-agatoxin-IVA. The Ca2+-dependent reversibility and promiscuity of this toxin may make it highly useful experimentally and therapeutically.