Central illustration: cumulative major adverse cardiac events (MACE) and bioresorbable vascular scaffold (BVS) thrombosis rates after 1, 2, 3, 4 and 5 years.相似文献
We describe the preclinical development of a dengue virus vaccine targeting the dengue virus serotype 2 (DENV2) envelope domain III (EDIII). This study provides proof-of-principle that a dengue EDIII protein scaffold/DNA vaccine can protect against dengue challenge. The dengue vaccine (EDIII-E2) is composed of both a protein particle and a DNA expression plasmid delivered simultaneously via intramuscular injection (protein) and gene gun (DNA) into rhesus macaques. The protein component can contain a maximum of 60 copies of EDIII presented on a multimeric scaffold of Geobacillus stearothermophilus E2 proteins. The DNA component is composed of the EDIII portion of the envelope gene cloned into an expression plasmid. The EDIII-E2 vaccine elicited robust antibody responses to DENV2, with neutralizing antibody responses detectable following the first boost and reaching titers of greater than 1:100,000 following the second and final boost. Vaccinated and naïve groups of macaques were challenged with DENV2. All vaccinated macaques were protected from detectable viremia by infectious assay, while naïve animals had detectable viremia for 2–7 days post-challenge. All naïve macaques had detectable viral RNA from day 2–10 post-challenge. In the EDIII-E2 group, three macaques were negative for viral RNA and three were found to have detectable viral RNA post challenge. Viremia onset was delayed and the duration was shortened relative to naïve controls. The presence of viral RNA post-challenge corresponded to a 10–30-fold boost in neutralization titers 28 days post challenge, whereas no boost was observed in the fully protected animals. Based on these results, we determine that pre-challenge 50% neutralization titers of >1:6000 correlated with sterilizing protection against DENV2 challenge in EDIII-E2 vaccinated macaques. Identification of the critical correlate of protection for the EDIII-E2 platform in the robust non-human primate model lays the groundwork for further development of a tetravalent EDIII-E2 dengue vaccine. 相似文献
A controlled, double-masked, randomized study was conducted on ten subjects to determine the effect of fenestration size on the initial comfort of hydrogel contact lenses. Four fenestrated lenses were tested, each lens containing four mid-peripheral fenestrations of the same size. The diameter of the fenestrations used in the four lenses ranged from 0.39 to 0.96 mm. An unfenestrated lens was also tested. All lenses were made of HEMA and were ordered with the following specifications: -3.00 D, 14.0 mm diameter, 8.4 mm back central optic radius and 0.06 mm centre thickness. There was a significant negative correlation between comfort and fenestration size, indicating that larger fenestrations are less comfortable. Even the lens with the smallest fenestrations (0.39 mm) was significantly less comfortable than the unfenestrated lens. The implication of this finding is that fenestrations may not be clinically efficacious in view of the poor comfort (and presumably increased mechanical effect of the fenestration edges on the tarsal conjunctiva) of fenestrated lenses. 相似文献