A Phase 1 Trial of MSP2-C1, a Blood-Stage Malaria Vaccine Containing 2 Isoforms of MSP2 Formulated with Montanide® ISA 720

Background: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2), parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naïve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion. Methodology/Principal Findings: The trial was designed to include three dose cohorts (10, 40, and 80 μg), each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 μg dose; no subjects received the 80 μg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 μg and 40 μg dose cohorts, with antibody levels by ELISA higher in the 40 μg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI) of parasite growth. Conclusions/Significance: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation of MSP2 in an alternative adjuvant. Trial Registration: Australian New Zealand Clinical Trials Registry 12607000552482

Multinuclear NMR spectroscopic studies of aryltrimethylsilanes and aryldimethylphosphaneboranes

Proton, boron-11, carbon-13, silicon-29, and phosphorus-31 NMR chemical shifts and coupling constants are reported for nine ortho- and 2,6-disubstituted aryltrimethylsilanes and five similarly substituted aryldimethylphosphaneboranes. Resonances in the natural-abundance carbon-13 NMR spectra for both sets of derivatives are assigned on the basis of additivity relationships, proton-coupled spectra, and relative magnitudes of | J(31P13C) | coupling constants. Carbon-13 chemical shifts and |1J(13C1H) | coupling constants indicate that the P(BH3)(CH3)2 group is electron-withdrawing. The 13C chemical shifts of aryl C(5) carbons can be attributed to steric inhibition of resonance of about the same magnitude as that produced by ortho-Si(CH3)3. Chemical shift and coupling constant data from previous work are expanded in terms of Taft\u27s dual substituent constants σ1 and σR0. Least squares solutions of these equations for aryldimethylphosphaneborane derivatives provide values of 0.41 for σ1 and 0.04 for σR0 for the P(BH3)(CH3)2 group. These constants produce reasonable agreement with observed 13C chemical shifts and coupling constants in the ortho derivatives. © 1989

Driving Force Dependence of Electron Transfer from Electronically Excited [Ir(COD)(μ-Me_2pz)]_2 to Photo-Acid Generators

We report the rates of electron transfer (ET) reactions of electronically excited [Ir(COD)(μ-Me_2pz)]_2 with onium salt photoacid generators (PAGs). The reduction potentials of the PAGs span a large electrochemical window that allows determination of the driving force dependence of the ET reactions. Rate constants of ET from electronically excited [Ir(COD)(μ-Me_2pz)]_2 to onium PAGs are determined by the reaction driving force until the diffusion limit in acetonitrile is reached

Is a prostate cancer screening anxiety measure invariant across two different samples of age-appropriate men?

<p>Abstract</p> <p>Background</p> <p>In order to explore the influence of anxiety on decision–making processes, valid anxiety measures are needed. We evaluated a prostate cancer screening (PCS) anxiety scale that measures anxiety related to the prostate–specific antigen (PSA) test, the digital rectal examination (DRE), and the decision to undergo PCS (PCS-D) using two samples in different settings.</p> <p>Methods</p> <p>We assessed four psychometric properties of the scale using baseline data from a randomized, controlled decision aid trial (n = 301, private clinic; n = 149, public).</p> <p>Results</p> <p>The 3-factor measure had adequate internal consistency reliability, construct validity, and discriminant validity. Confirmatory factor analyses indicated that the 3–factor model did not have adequate fit. When subscales were considered separately, only the 6–item PCS-D anxiety measure had adequate fit and was invariant across clinics.</p> <p>Conclusions</p> <p>Our results support the use of a 6–item PCS-D anxiety measure with age-appropriate men in public and private settings. The development of unique anxiety items relating to the PSA test and DRE is still needed.</p