A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

Strategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged >= 65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 mu g of A/H1N1 and B, differing in A/H3N2 content (6 mu g or 12 mu g), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 mu g of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 mu g or 30 mu g) and/or in MF59 (R) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P < 0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P < 0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery

MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate

His+ reversions Caused in Salmonella typhimurium by different types of ionizing radiation

The yield of his+ reversions in the Ames Salmonella tester strain TA2638 has been determined for 60Co γ rays, 140 kV X rays, 5.4 keV characteristic X rays, 2.2 MeV protons, 3.1 MeV α particles, and 18 MeV/U Fe ions. Inactivation studies were performed with the same radiations. For both mutation and inactivation, the maximum effectiveness per unit absorbed dose was obtained for the characteristic X rays, which have a dose averaged linear energy transfer (LET) of roughly 10 keV/μm. The ratio of the effectiveness of this radiation to γ rays was 2 for inactivation and about 1.4 for the his+ reversion. For both end points the effectiveness decreases substantially at high LET, i.e., for the α particles and the Fe ions. The composition of the bottom and the top agar was the one recommended by Maron and Ames [Mutat. Res. 113, 173-215 (1983)] for application in chemical mutagenicity tests. The experiments with the less penetrating radiations differed from the usual protocol by utilization of a technique of plating the bacteria on the surface of the top agar. As in an earlier study [Roos et al., Radiat. Res. 104, 102-108 (1985)] greatly enhanced yields of mutations, relative to the spontaneous reversion rate, were obtained in these experiments by performing the irradiations 6 h after plating, which differs from the conventional procedure to irradiate the bacteria shortly after plating

Dosimetric Comparison of VMAT, IMRT and Proton Therapy for Post- Prostatectomy Radiation Therapy for Prostate Cancer

Purpose/Objectives: Radiation therapy (RT) for the treatment of prostate cancer after radical prostatectomy (RP) is widely accepted. With technological advances, radiation treatment technique and dosimetry may vary. The purpose of this study is to quantify dosimetric difference of proton therapy versus VMAT and IMRT focusing on bladder and rectal dose sparing and target coverage. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Quantitative and qualitative analysis of antibody response after dose sparing intradermal 2009 H1N1 vaccination

Letter to the editorpostprin

An Automated Treatment Plan Quality Control Tool for Intensity-Modulated Radiation Therapy Using a Voxel-Weighting Factor-Based Re-Optimization Algorithm.

Intensity-modulated radiation therapy (IMRT) currently plays an important role in radiotherapy, but its treatment plan quality can vary significantly among institutions and planners. Treatment plan quality control (QC) is a necessary component for individual clinics to ensure that patients receive treatments with high therapeutic gain ratios. The voxel-weighting factor-based plan re-optimization mechanism has been proved able to explore a larger Pareto surface (solution domain) and therefore increase the possibility of finding an optimal treatment plan. In this study, we incorporated additional modules into an in-house developed voxel weighting factor-based re-optimization algorithm, which was enhanced as a highly automated and accurate IMRT plan QC tool (TPS-QC tool). After importing an under-assessment plan, the TPS-QC tool was able to generate a QC report within 2 minutes. This QC report contains the plan quality determination as well as information supporting the determination. Finally, the IMRT plan quality can be controlled by approving quality-passed plans and replacing quality-failed plans using the TPS-QC tool. The feasibility and accuracy of the proposed TPS-QC tool were evaluated using 25 clinically approved cervical cancer patient IMRT plans and 5 manually created poor-quality IMRT plans. The results showed high consistency between the QC report quality determinations and the actual plan quality. In the 25 clinically approved cases that the TPS-QC tool identified as passed, a greater difference could be observed for dosimetric endpoints for organs at risk (OAR) than for planning target volume (PTV), implying that better dose sparing could be achieved in OAR than in PTV. In addition, the dose-volume histogram (DVH) curves of the TPS-QC tool re-optimized plans satisfied the dosimetric criteria more frequently than did the under-assessment plans. In addition, the criteria for unsatisfied dosimetric endpoints in the 5 poor-quality plans could typically be satisfied when the TPS-QC tool generated re-optimized plans without sacrificing other dosimetric endpoints. In addition to its feasibility and accuracy, the proposed TPS-QC tool is also user-friendly and easy to operate, both of which are necessary characteristics for clinical use

The use of out-of-plane high Z patient shielding for fetal dose reduction in computed tomography: Literature review and comparison with Monte-Carlo calculations of an alternative optimisation technique.

When performing CT examinations on pregnant patients, great effort should be dedicated towards optimising the exposure of the mother and the conceptus. For this purpose, many radiology departments use high-Z garments to be wrapped around the patient's lower abdomen for out-of-plane organ shielding to protect the fetus. To assess their current protection efficiency, we performed a literature review and compared the efficiencies mentioned in the literature to Monte-Carlo calculations of CT protocols for which the overall scan length was reduced. We found 11 relevant articles, all of them reporting uterus exposure due to CT imaging performed for exclusion of pulmonary embolism, one of the leading causes of peripartum deaths in western countries. Uterus doses ranged between 60 and 660 µGy per examination, and relative dose reductions to the uterus due to high-Z garments were between 20 and 56%. Calculations showed that reducing the scan length by one to three centimetres could potentially reduce uterus dose up to 24% for chest imaging, and even 47% for upper abdominal imaging. These dose reductions were in the order of those achieved by high-Z garments. However, using the latter may negatively influence the diagnostic image quality and even interfere with the automatic exposure control system thus increasing patient dose if positioned in the primary beam, for example in the overranging length in helical acquisition. We conclude that efforts should be concentrated on positioning the patient correctly in the gantry and optimising protocol parameters, rather than using high-Z garments for out-of-plane uterus shielding