Human immune response to a plague vaccine comprising recombinant F1 and V antigens.

The human immune response to a new recombinant plague vaccine, comprising recombinant F1 (rF1) and rV antigens, has been assessed during a phase 1 safety and immunogenicity trial in healthy volunteers. All the subjects produced specific immunoglobulin G (IgG) in serum after the priming dose, which peaked in value after the booster dose (day 21), with the exception of one individual in the lowest dose level group, who responded to rF1 only. Three subjects, found to have an anti-rV titer at screening, were excluded from the overall analysis. Human antibody functionality has been assessed by quantification of antibody competing for binding to rV in vitro and also by the transfer of protective immunity in human serum into the naive mouse. Human and macaque IgG competed for binding to rV in vitro with a mouse monoclonal antibody, previously shown to protect mice against challenge with plague, suggesting that this protective B-cell epitope on rV is conserved between these three species. Total IgG to rV in individuals and the titer of IgG competing for binding to rV correlated significantly at days 21 (r = 0.72; P < 0.001) and 28 (r = 0.82; P < 0.001). Passive transfer of protective immunity into mice also correlated significantly with total IgG titer to rF1 plus rV at days 21 (r(2) = 98.6%; P < 0.001) and 28 (r(2) = 76.8%; P < 0.03). However, no significant vaccination-related change in activation of peripheral blood mononuclear cells was detected at any time. Potential serological immune correlates of protection have been investigated, but no trends specific to vaccination could be detected in cellular markers.

The electrostability and electrically assisted delivery of an organophosphate pretreatment (physostigmine) across human skin in vitro.

Physostigmine is a tertiary carbamate that is utilised as a pretreatment against organophosphate intoxication. Oral delivery of physostigmine is not practical due to high first pass metabolism and short elimination half life. Transdermal administration of physostigmine may circumvent such problems. The aim of this study was to assess the electrostability of physostigmine and the feasibility of electrically assisted transdermal drug delivery of physostigmine through isolated human skin in vitro. Buffered solutions of physostigmine (free base, salicylate and sulphate) were electrostable under conditions of iontophoresis and electroporation as measured by HPLC, although instability of the chloridised silver electrodes was observed. Physostigmine sulphate was chosen for further study as it appeared to prevent degradation of the electrodes. Under conditions of iontophoresis (0.8 mA cm(-2), applied for 5- or 2.5-min durations for a maximum period of 45 min over 8 h), the total quantity of physostigmine sulphate that penetrated was 6.5+/-2.3% and 3.9+/-1.7% (pH 5.0 and pH 5.5) of the total applied dose (2 mg). Physostigmine did not penetrate the skin when electroporated at a frequency of 0.1 Hz or 10 Hz (100 V, 1 ms pulse width, duration 1 s, repetition 5-10 s), but significant amounts were delivered at a frequency of 100 Hz, being 11.3+/-2.9% and 5.8+/-2.5% of the applied dose (pH 5.0 and pH 5.5, respectively). These data indicate that iontophoretic and electroporative drug delivery of physostigmine sulphate was buffer-dependent, an effect tentatively attributed to a combination of co-ion competition, mono/di-cation ratio and applied charge effects.

Comparison of the attitudes of hospital dentists and dental students in Glasgow, UK and Los Angeles, USA towards treatment of AIDS and hepatitis B patients.

A transcultural comparison of the attitudes of hospital dental practitioners and final year dental students in Glasgow, Scotland and Los Angeles, USA was made to assess their attitudes towards treatment of AIDS and hepatitis B patients. Almost all of the respondents were aware of the facts related to spread of AIDS via saliva and blood and the major oral manifestations of AIDS. Surprisingly, a significant proportion of respondents in both countries said they will not attend their dentist if the latter treats AIDS patients and significantly more Americans thought that AIDS transmission was likely in the dental clinic. An overwhelming majority thought specially trained dentists should be employed to treat AIDS patients while the majority of Americans, as compared with Scots surmised that AIDS is a serious threat to public health. In general, the attitudes of the two survey populations towards the AIDS epidemic and attendant problems was similar although the Scots were more complacent than their American counterparts, probably due to the less immediacy of the AIDS problem in Scotland.