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- Hu, Jinhong, et al.
(författare)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 2. |
- Sun, Mengtao, et al.
(författare)
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Chemical mechanism of surface-enhanced resonance Raman scattering via charge transfer in pyridine-Ag-2 complex
- 2008
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Ingår i: Journal of Raman Spectroscopy. - : Wiley. - 1097-4555 .- 0377-0486. ; 39:3, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- A theoretical model is presented to describe the chemical mechanism of surface-enhanced resonance Raman scattering (SERRS) via charge transfer (CT) in the pyridine-Ag-2 complex. We first describe the influence of the interaction between the metal cluster and pyridine to the ground-state properties of the pyridine-Ag-2 complex, such as charge redistribution, the change of the atomic-resolved density of state, and the change of energy levels of occupied and unoccupied molecular orbitals. Second, we visualize the CT between the metal cluster and pyridine and within the intracluster on the electronic state transitions with charge difference density. The CT between the metal cluster and pyridine is the direct evidence of chemical mechanism for SERRS. Third, the spectra of SERRS are calculated with different incident light wavelengths that resonate with the different electronic state energy levels, and the enhanced intensities of different vibrational modes are compared, which show that there are different enhancement rates for different vibrational modes. Strong Raman scattering can be achieved not only by the CT between pyridine and the metal cluster but also by electronic intracluster excitation via a type of Forster excitation transfer, and the latter results from the local field effects by collective plasmons. The selection rules for the SERRS have been obtained for these two types of enhanced mechanisms. Copyright (C) 2008 John Wiley & Sons, Ltd.
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