Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination:Preparation, characterization and evaluation in guinea pigs

this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercritical fluid (SCF) spraying process. The median volume diameter of the dry particles, as determined by laser diffraction analysis, was between 2 and 3 mu m and the fine particle mass fractions smaller than 5 mu m, as determined by cascade impactor analysis, were 35 and 56% for the dextran and TMC formulations, respectively. The water content of the particles as measured by Karl-Fischer titration was 2-3% (w/w). Pulmonary immunization with DT-TMC microparticles containing 2 or 10 Lf of DT resulted in a strong immunological response as reflected by the induction of IgM, IgG, IgG subclasses (IgG1 and IgG2) antibodies as well as neutralizing antibody titers comparable to or significantly higher than those achieved after subcutaneous (SC) administration of alum-adsorbed DT (2 Lf). Moreover, the IgG2/IgG1 ratio after pulmonary immunization with DT-TMC microparticles was substantially higher as compared to SC administered alum-adsorbed DT. In contrast, pulmonarily administered DT-dextran particles were poorly immunogenic. Among the tested formulations only pulmonarily administered DT-contairling TMC microparticles induced detectable pulmonary secretory IgA levels. In conclusion, in this paper it is demonstrated that TMC microparticles are a potent new delivery system for pulmonary administered DT antigen. (c) 2007 Elsevier Ltd. All rights reserved

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis : Prospective cohort study of a nationwide programme in the Netherlands

Objective To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD. Design Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined. Setting Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting. Participants 25 789 RhD negative pregnant women. Main outcom e measures Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. Results A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. Conclusions Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis : Prospective cohort study of a nationwide programme in the Netherlands

Objective To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD. Design Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined. Setting Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting. Participants 25 789 RhD negative pregnant women. Main outcom e measures Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. Results A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. Conclusions Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use

Animal models for cutaneous vaccine delivery

Drug Delivery Technolog