简介：CpGoligodeoxynucleotides(CpGODN)asadjuvanthavebeenextensivelystudiedinrecentyears.PhosphodiesterCpGODN(POCpGODN)canperfectlymimicbacterialDNAinenhancingimmuneresponsebutarevulnerabletonucleasesinvivo.ThisstudyaimedtoevaluatetheimmunostimulatorypotentialandsafetyofphosphodiesterCpGODNencapsulatedinnonphospholipidliposomes.BALB/cmicewereimmunizedintramuscularlywithdifferentformulationsofliposomes,CpGODNandhepatitisBsurfaceantigen(HBsAg).TheresultsdemonstratedthattheencapsulatedPOCpGODNwereprotectedagainstrapiddegradationinvivoandretainedtheiradjuvantactivity.POCpGODNencapsulatedwithHBsAginliposomesinducedstrongTh1-biasedorTh1/Th2mixedhumoralimmuneresponseinmicewiththemagnitudesimilartotheirphosphothioateequivalentinthesameformulation.HighIFN-gammaproductioninducedbythisformulationconfirmedthegenerationofstrongcellularimmuneresponse.Additionally,co-deliveryofHBsAgandPOCpGODNimprovedtheimmuneresponseoverthatobtainedwithseparatedelivery.Safetyexperimentshowedthatliposome-encapsulaedPOCpGODNandHBsAgcausedmildsystemicandmoderatelocaladversereaction.Inconclusion,ourdatashowsthatPOCpGODNencapsulatedinliposomesfullyexhibittheirTh1-typeadjuvantactivityandactasapotentialadjuvantforvaccines.

简介：Severeacuterespiratorysyndrome(SARS)emergedin2002asasevereandhighlycontagiousinfectiousdiseasethatrapidlyspreadtoanumberofdifferentcountries.Thecollaborativeeffortsoftheglobalscientificcommunityhaveprovided,withinashortperiodoftime,substantialinsightsintothemolecularbiologyandimmunologyofSARS-CoV.Althoughtheoutbreakhasbeencontained,thereiscontinuousconcernthatthevirusmayresurfaceintothehumanpopulationthroughseasonalchanges,animalreservoirsorlaboratoryaccidents.TheseveremorbidityandmortalityassociatedwithSARSmakeitimperativethataneffectivevaccinebedevelopedtopreventreemergenceandepidemicsinthefuture.Cellular&MolecularImmunology.2005;2(2):101-105.

简介：DevelopingawidelyadaptableAIDSvaccineisthegoalofscientistswhofightagainstglobalproliferationofthedeadlydisease.NoW,somearefocusingtheirstudyonChina,believingthatthecountrymaybetheperfectpartnerforacollaborationinvaccineresearch.AninternationalAIDSvac...

简介：Flaviviruses包括约70个密切相关的RNA病毒。这些包括几忍受蚊子的病原体，例如黄发烧病毒(YFV)，登革热病毒(DENV)，和日本脑炎病毒(JEV)，它能引起重要人的疾病并且因此具有大医药重要性。对YFV和JEV的疫苗为decades;在人成功地被使用了；然而，一支DENV疫苗的发展遇到了可观的障碍。这里，我们考察疫苗对YFV得到提供一些卓见进一支保护的DENV疫苗的发展的保护的有免疫力的回答。

简介：Everydaywealluseroads.Wewalkonthem.Wewalkeitheralongthepavement(人行道)oracrosstheroad.Ifwearecareless,wecancauseaccidents.Accidentsoftenhappenwhenpeoplearecrossingtheroad.Hereissomeadvice.

简介：大家对闪电再熟悉不过了。可闪电是怎样形成的呢?当狂风大作、电闪雷鸣时，我们应该注意些什么呢?

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简介：Inabreakthroughthatcouldrevolutionizehumanity'srelationshipwithillnessanddisease,amethodofvaccinationhasbeendevelopedthatprovidesinstantimmunity,USresearchersannouncedMonday.

简介：AbstractBackground:Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95% CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx? proj=124702).

简介：AbstractBackground:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.Methods:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx? proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

简介：AbstractGlioblastoma (GBM) is the most common primary malignancy of the central nervous system in adults. The prognosis for late-stage glioblastoma (World Health Organization grade IV astrocytic glioma) is very poor. Novel treatment options are sought after and evaluated by clinicians and researchers, and remarkable advances have been made in surgical techniques, radiotherapy, and chemotherapy. However, the treatment of glioblastoma remains extremely difficult and it can extend the lives of patients by only a few months. There has been notable progress in the field of immunotherapy, particularly with the use of tumor vaccines, for treating glioblastoma; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines. However, the results of the current clinical trials for vaccination are not satisfactory. This article reviews the progress in the development of vaccines for glioblastoma.

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简介：NevergiveoutidentifyingsuchasHomeAddress,SchoolName,orTelephoneberinapublicmessagesuchasatachatName,Num-roomoronbulletinboards.Neversendapersonapic-tureofyouwithoutfirstcheckingwithyourpar-

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简介：Trafficruleisakeyfactoraffectingtrafficflowandsafety.Wedevelopourmodels,includingthecellularautomatatrafficflowmodelaswellasthelinearregressionone,aimingatcalculatingtrafficflowandevaluatingsafetyconditionswithvariedtrafficrules.Then,wethoroughlyinvestigatefourtypesofpathsinafreeway,namelytwostraightlanes,threestraightlanes,ramps,androundaboutsascasestudiesanddiscussthedifferenttrafficrulesascomparison.Theresultsdemonstratethat“Keep-Right-Except-To-Pass”ruleisnotaseffectiveasthefreeruleinpromotingtrafficflow;however,thisruleensuressafetyfordriversbetterthanthefreerule.Additionally,anewtrafficrule,whichsetsdifferentpostedspeedlimitsforadjacentlanes,isproposedtopromotebettertrafficflowwithsafetyrequirementssatisfied.Furthermore,weapplyeffectiverulesandalternatives,leftdrivingnormsaswellasintelligentsystemasextensionandobtainbetterresults.Finally,model’ssensitivityanalysisregardingtoprobabilityofdeceleratingandpostedspeedlimitsprovesthestabilityofourresults.

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简介：Inordertoinvestigatetheimmtmogenicityofthecontrolled-releasemicroencapsulatedhepatitisBvaccineinmice,polyethyleneglycol-poly-dl-lactide(PELA)microsphereswithentrappedHSsAgwerepreparedbydoubleemulsionW/O/Wbasedonsolventextractionmethods.BALB/cmicewereimmunizedwiththeencapsulatedvaccinebyoralfeedingorinjection.Bloodsampleswerecollectedat8^th,10^th,14^thand24^thweeks,respectively,andthelevelsofantibodyresponseweredetectedbyEI.ISA.Itwasfoundthatthescanningelectronmicroscopyshowedthepreparedmicrosphereshadsmoothandsphericalsurface,suitableforvaccinedelivery.Twogroupsofmiceorallyfedwiththeencapsulatedorconventionalrecombinantvaccines,respectively,theresereshowednoobviousdifferenceintheIgGlevels.At14^thweek,thegroupinjectedwithasingledoseofencapsulatedvaccinehadasimilarlevelofIgGresponsetothegroupinjectedwithtwodosesoftherecombinationvaccine.At24^thweek,theIgGlevelsofthegroupinjectedwithtwodosesofencapsulatedvaccinewerehigherthanthoseofthegroupinjectedwithtwodosesoftherecombinationvaccine.ItconcludesthatControlled-releasemicroencapsulatedhepatitisBvaccinepossessesthefeatureofslowlyreleasinginv/voandlongtimesimmtmogenicity.

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