據(jù)英國(guó)路透社報(bào)道,美國(guó)科學(xué)家于1月10日表示,初期臨床試驗(yàn)表明用轉(zhuǎn)基因牛生產(chǎn)的人類(lèi)抗體是安全的,并可能被開(kāi)發(fā)成一種對(duì)抗MERS-CoV的療法。
中東呼吸綜合征(MERS)是2012年在沙特阿拉伯首次發(fā)現(xiàn)的類(lèi)似于SARS的病毒,在中東引發(fā)了致命的疫情,在世界各地也有零星病例。盡管有超過(guò)五年接連不斷的感染,但目前還沒(méi)有研制出有效的療法或
疫苗對(duì)抗MERS,該病毒導(dǎo)致的病死率高達(dá)35%,迄今已造成全球至少740人死亡。
據(jù)世界衛(wèi)生組織稱(chēng),超過(guò)80%的MERS病例已在沙特阿拉伯發(fā)現(xiàn)。在10日發(fā)表在英國(guó)《LancetInfectDis.》雜志上的一項(xiàng)研究中,科學(xué)家們發(fā)現(xiàn),在跨染色體牛(將人類(lèi)DNA整合到其基因組中的牛)身上產(chǎn)生的名為SAB-301的人類(lèi)抗體在健康志愿者的身體中是安全的。研究發(fā)現(xiàn),這些抗體持續(xù)的時(shí)間比MERS病毒在體內(nèi)的持續(xù)時(shí)間還要長(zhǎng),90天后血液中仍能檢測(cè)到抗體。研究人員說(shuō),這為這些能增強(qiáng)抗侵入性感染的免疫力的抗體在MERS感染者的進(jìn)一步試驗(yàn)中進(jìn)行測(cè)試指明了方向。
“這是首例說(shuō)明MERS潛在治療方法安全性和免疫效果的研究,我們的研究數(shù)據(jù)表明SAB-301抗體是安全的,有必要對(duì)其進(jìn)行進(jìn)一步的研究。”萊多斯生物醫(yī)學(xué)研究的約翰貝格爾(JohnBeigel)如是說(shuō)。他曾參與和領(lǐng)導(dǎo)美國(guó)政府資助的這項(xiàng)研究。
近年來(lái)使用人類(lèi)抗體的想法在各種重疾和新出現(xiàn)的疾病中得到發(fā)展,包括
流感、嚴(yán)重急性呼吸綜合征(SARS)、MERS和埃博拉(Ebola)。那些免疫系統(tǒng)成功地打敗該疾病的人的血漿中含有正確的抗體,如果收集這些血漿并給予其他患者,就可以幫助這些患者的免疫系統(tǒng)對(duì)
抗病毒。但是這并不容易和便捷,當(dāng)一種新的疾病出現(xiàn)時(shí),科學(xué)家們更傾向于用跨染色體牛的方法來(lái)大量制造需要的抗體。跨染色體牛有人類(lèi)的DNA,人類(lèi)抗體納入其基因組編碼。為了得到sab-301抗體,部分MERS病毒被注入到跨染色體牛體內(nèi),以刺激其免疫系統(tǒng)產(chǎn)生抗體。然后從牛的血液中提取抗體并純化。
貝格爾說(shuō):“從人類(lèi)捐獻(xiàn)者體中收集抗體以對(duì)抗抗體治療的過(guò)程緩慢,通常是小規(guī)模的。然而,牛生產(chǎn)的抗體可以在三個(gè)月內(nèi)就被產(chǎn)生出來(lái)。”
參考文章:Safetyandtolerabilityofanovel,polyclonalhumananti-MERScoronavirusantibodyproducedfromtranschromosomiccattle:aphase1randomised,double-blind,single-dose-escalationstudy
參考摘要:
Background:MiddleEastrespiratorysyndrome(MERS)isasevererespiratoryillnesswithanoverallmortalityof35%.Thereisnolicensedorproventreatment.Passiveimmunotherapyapproachesarebeingdevelopedtopreventandtreatseveralhumanmedicalconditionswherealternativetherapeuticoptionsareabsent.WereportthesafetyofafullyhumanpolyclonalIgGantibody(SAB-301)producedfromthehyperimmunepla
smaoftranschromosomiccattleimmunisedwithaMERScoronavirusvaccine.
Methods:Wedidaphase1double-blind,placebo-controlled,single-doseescalationtrialattheNationalInstitutesofHealthClinicalCenter.Werecruitedhealthyparticipantsaged18-60yearswhohadnormallaboratoryparametersatenrolment,abody-massindexof19-32kg/m2,andacreatinineclearanceof70mL/minormore,andwhodidnothaveanychronicmedicalproblemsthatrequireddailyoralmedications,apositiverheumatoidfactor(≥15IU/mL),IgAdeficiency(<7mg/dL),orhistoryofallergytointravenousimmunoglobulinorhumanbloodproducts.Participantswererandomlyassignedbyacomputer-generatedtable,madebyamaskedpharmacist,tooneofsixcohorts(containingbetweenthreeandtenparticipantseach).Cohorts1and2hadthreeparticipants,randomlyassigned2:1toreceiveactivedrugSAB-301versusnormalsalineplacebo;cohorts3and4hadsixparticipantsrandomised2:1;andcohorts5and6hadtenparticipants,randomised4:1.Participantsreceived1mg/kg,2·5mg/kg,5mg/kg,10mg/kg,20mg/kg,or50mg/kgofSAB-301,orequivalentvolumeplacebo(salinecontrol),onday0,andwerefollowedupbyclinical,laboratory,andpharmacokineticassessmentsondays1,3,7,21,42,and90.Theprimaryoutcomewassafety,andimmunogenicitywasasecondaryoutcome.Weanalysedtheintention-to-treatpopulation.ThistrialisregisteredwithClinicalTrials.gov,numberNCT02788188.
Finding:BetweenJune2,2016,andJan4,2017,wescreened43participants,ofwhom38wereeligibleandrandomlyassignedtoreceiveSAB-301(n=28)orplacebo(n=10).97adverseeventswerereported:64adverseeventsoccurredin23(82%)of28participantsreceivingSAB-301(mean2·3adverseeventsperparticipant).33adverseeventsoccurredinalltenparticipantsreceivingplacebo(mean3·3adverseeventsperparticipant).Themostcommonadverseeventswereheadache(n=6[21%]inparticipantswhoreceivedSAB-301andn=2[20%]inthosereceivingplacebo),albuminuria(n=5[18%]vsn=2[20%]),myalgia(n=3[11%]vsn=1[10%]),increasedcreatinekinase(n=3[11%]vs1[10%]),andcommoncold(n=3[11%]vsn=2[20%]).Therewasoneseriousadverseevent(hospitaladmissionforsuicideattempt)inoneparticipantwhoreceived50mg/kgofSAB-301.Theareaundertheconcentration-timecurve(AUC)inthe50mg/kgdose(27?498μg?×?dayspermL)iscomparabletotheAUCthatwasassociatedwithefficacyinapreclinicalmodel.
Interpretation:SingleinfusionsofSAB-301upto50mg/kgappeartobesafeandwelltoleratedinhealthyparticipants.HumanimmunoglobulinderivedfromtranschromosomiccattlecouldofferanewplatformtechnologytoproducefullyhumanpolyclonalIgGantibodiesforothermedicalconditions.
Funding:NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth,andBiomedicalAdvancedResearchandDevelopmentAuthority.