Gerald W. Parker

Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans.

Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months. To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route. We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route). IM administration of AVA was associated with fewer injection site reactions than SQ administration. Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001). Reaction rates decreased with a longer dose interval between the first two doses. The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals. The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart. A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.

Anthrax vaccine: increasing intervals between the first two doses enhances antibody response in humans

The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In both studies, the interval between the first two doses was 2, 3 or 4 weeks. In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine. In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA. In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (p=0.0005-0.029). In the first study, the seroconversion rate also increased as the interval between the first two doses increased (p=0. 0034). A prospective, randomized study has been completed and is being analyzed to confirm these findings.

Non-specific binding of palytoxin to plastic surfaces

The changes in blood pressure induced by palytoxin (PTX) administered intravenously through polyethylene (PE) tubing were varied, suggesting either non-specific binding of the toxin to PE or deactivation. By spectrophotometry and HPLC, we found that PTX bound non-specifically to PE tubing and that this binding was attenuated by adding 0.1% rat serum albumin. Furthermore, the chemical stability and activity of PTX were not affected by exposure to room light and/or room temperature. Biological deactivation was excluded as a cause of the observed variability because the hypertensive and lethal effects of infused PTX, delayed with simultaneous administration of sodium nitroprusside (NNP), were in full evidence when the NNP was discontinued 35 min later.