Ejongene nemingcipheko ekuphuhliseni isitofu sokugonywa kwe-HIV , izazinzulu ziye zabeka ingqwalasela enkulu kwiminyaka yakutshanje ekufumaneni iinkqubo zokuzikhusela ezikhuselekileyo eziza kunceda umzimba ukuba ulwe, okanye uthintele, ukusuleleka koGawulayo.
Ubungqina bolu hlobo bunamandla. Siye sazi, umzekelo, ukuba kukho i-subset yabantu abathiwa abalawuli abaphezulu ababonakala bakwazi ukulawula i-HIV ngaphandle kokusetyenziswa kweziyobisi.
Xa sibhekisisa aba bantu, abaphandi baye bakwazi ukuhlukanisa inani lezinto ezinxulumene nalo khuselo lwendalo.
Oyintloko phakathi kwezi zi-proteins ezibizwa ngokuba yi- bNAbs , eziqhelekileyo zibonwa kubalawuli abakhulu kwaye, ngokungafani ne-antibodies, ziyakwazi ukunciphisa iindidi ezahlukeneyo ze-HIV .
NgoNovemba ka-2016, izazinzulu ngeZiko lezeMpilo zeSizwe zazisa ukufumanisa i-BNAb entsha, ebizwa ngokuba yi-N6, eyakwazi ukuphucula i-98 pesenti yazo zonke iintsholongwane ze-HIV kwiimvavanyo zelabhu zangaphambili. Le ncwadana ye-immune yomnxeba, eyahlukana nomlawuli we-HIV e-elite, kwathiwa ngamaxesha angama-10 aphumelele ekubulaleni i-HIV kunanoma yimuphi na owaziwa ngoku.
Ukuqonda ngokubanzi Ukunciphisa i-Antibodies
Ama-antibodies anama-proteins enziwe nge-Y aveliswa ngamajoni omzimba wokunceda ukulwa nezifo ezibangelwa zizifo ezifana ne-bacteria okanye ii-virus.
Ngokubanzi, ininzi iqulunqwe ukulwa nohlobo olulodwa lwe-pathogen kunye ne-one-pathogen yodwa-imeko eyingxaki enikwe ukuba i- HIV ihlala iguqule kwaye iyakwazi ukufumanisa ukufunyanwa nje ngokungaqondakali kumntu okhuselayo.
Ngokwahlukileyo, i-BBB iyakwazi ukulandelela i-HIV kwanokuba ihlaziye kwaye iguqule, ichonga intsholongwane kungekhona ngoqulunqo lwayo lwezakhiwo kodwa i-receptors phezu kwentsholongwane (ebizwa ngokuba yi-CD4 e-binding sites), ezingenakukwazi ukutshintsha.
Nangona i-bBbs ihlala iqukunjelwa ngokulawulwa kwabantu abaphezulu, baya kuthi bakhulume kubo bonke abantu abanentsholongwane kaGawulayo, nangona kunjalo kwizinga elide kakhulu.
Kwabaninzi abalawuli be-elite, ubukho beBBbs bubhekwa njengento engenangqondo, oku kuthetha ukuba zikhoyo ngexesha losulelo. Kwi-controllers non-elite, i-BBB iya kubonakala ngokuqhelekileyo kwiminyaka engama-2-3 yokusuleleka kwintsholongwane, ngelo xesha intsholongwane iya kuzingena kwiiseli kunye nezicubu ezibizwa ngokuba ziindawo zokugcina , apho ziya kuhlala zifihliwe kwi-immune detection.
Iingcali ngoku zikholelwa ukuba ukuba ziyakwazi ukuvuselela i-immune system ukuba ivelise i-BNAbs "ngokufunwa," inokukwazi ukuthintela usulelo okanye ukuphucula inkqubo yesifo, ngaphandle okanye ngaphandle kokuncedisa amayeza.
Imbali yeNdalo yoLuntu ngokuMandla
Nangona iinqununu zaziqala ukufumanisa i-BNAbs ngasekuqaleni kwee-1990, bekuphela ngo-2009 ukuba abaviwa abaninzi abaphumelelayo baqwalasela abaphandi be-vaccine. Phakathi kwazo kwakuyi-VRC01, i-BNAb eyayisuswe kumntu wase-Afrika waseMelika kwaye kamva iboniswa ukuba iyanciphise iipesenti ezingama-90 yazo zonke i-HIV-1 strains.
I-VRC01 isebenza ngokuxhomekeka kwisayithi yokubopha i-CD4 kwindawo yesifo senqindi, ukukhusela i-HIV ukuba ingene kwisitokethi esiphezulu esichengeni.
Ukuhlolwa kwezilwanyana zakuqala ukuphanda i-VRC01 kubonise isithembiso, kunye nama-primates ajojowe ngama-antibodies abonisa ukulawulwa kwegciwane kwithuba leenyanga ezintandathu.
Uvavanyo lweziluntu, ngokuphambene, luye lwadanisa kakhulu. Ucwaningo olwenziwa ngo-2016 oluvela kwiqela le-AIDS Clinic Trial Group lubonise ukuba i-VRC01 ye-intravenous infusions, ngelixa ixineke kakuhle, ayizange incinci yokugcina ulawulo lwentsholongwane kubathathi-nxaxheba abaye baxothwa kwiziyobisi zabo. Iijoyile ezininzi azikwazanga ukuphucula kwezi ziphumo.
Ukufunyanwa kwe-anti-N6 entsha inokuqwalaselwa ngokubalulekayo phakathi kwalabo abayibona umzukeli wendalo kwi-VRC01, zombini ekuzalweni kwezofuzo kunye nobuchule.
Kwaye kukho ubungqina obunamandla bokuxhasa ezi mbono.
Kwangaphambili ukuya ku-N6, abaninzi abaviwa be-BNAb baye babanzi banzi kakhulu kodwa banobuchule obukhulu (njengokuba kunjalo neVRC01) okanye kunamandla kakhulu kodwa ngaphantsi. I-N6 ibonakala, ubuncinane kwizilingo zangaphambi kweklinikhi, ukuba isebenze kwimimandla yomibini, iyanciphise i-98% yezi-181 ezahlukeneyo ze-HIV (kuquka i-16 ye-20 i-immune iminyango kwezinye i-BNAB kwiklasi yayo).
Ubuninzi bokusebenza kwawo bunokuthiwa yinto engavumelekanga yongqingili, evumela ukuba iphephe i-carbohydrate "iminyango yomnyango" ekhusela ezinye i-BNAbs ekubeni ixhomekeke kwintsholongwane.
Ngaba i-N6 ivule iNdoqo ukuya kwiNtsholongwane kaGawulayo?
Ukuba i-N6 iyakwazi ukufezekisa iziphumo ezifanayo kwizilingo zomntu, kuba yinto yokuqala ye-ejenti ukuba inxephezele ukuhlukahluka kwe-HIV, kokubili kumgangatho wabantu kunye nabemi.
Oko akutshoyo akuyi kutshaya izithintelo ezifanayo ezibonwe kwiimvavanyo zokuqala zeVRC01, apho inoculation ngqo ehlulekile ukuphinda iphendule izibonelelo zolawulo oluphezulu. Ngokufanayo, kukho ubungqina obuncinane bokubonisa ukuba sinokunyusa amajoni omzimba ukuba avelise ezi zikhuhlane, ubuncinane ubuninzi ngokwaneleyo ukuba kuthathwa njengokhuselo.
Enye yemingeni emikhulu ebhekene nabaphandi kukuba i-bNAb enye ibonakaliswe nzima kakhulu. Ukuthetha ngokuqhelekileyo, xa izazinzulu zizama ukunyusa impendulo, umzimba uya kuphendula ngokuphendula okuphikisanayo, omnye owenza umonakalo. Ingundoqo yindlela yomzimba 'yokubeka iibhuleki' kwisistim somzimba sokuzivikela ekuqinisekiseni ukuba akukho nto iqhubekileyo (njengokuba kwenzeka ngezifo ezizimelayo ) okanye ingagunyazisiyo (njengokuba kwenzeka ngeengxaki zokuxhatshazwa ngumzimba).
Imiba engakumbi yokuxakeka yiindawo zokuhlala ezikhuselekileyo apho i-HIV inokuhlala ikhuselekile ekufunyaneni iminyaka kunye namashumi eminyaka. Ingxaki yile: yintsholongwane yokuqala yokujikeleza ingasetyenziswanga yi-bNAbs; ezo zifihlekile kwiindawo zokugcina izixhobo zamanzi azikwazi. Kuphela ngo "ukukhaba" i-HIV ngaphandle kokufihla ukuba i-BBbs inethuba lokwenza unyango olusisigxina. Isicwangciso esicwangcisiweyo esininzi, esaziwa ngokuba yi "kick-kill", namhlanje libhekwa njengento ephambili kwiinqela zophando lwe-HIV.
Ikamva le-BNAb Research
Ingaba izazinzulu ziya kunqoba nayiphi na le miqobo engabonakaliyo. Into esaziyo ngokuqinisekileyo kukuba i-N6 idlula nayiphi na enye i-BNAbs okwangoku iphandwayo, zombini ngobubanzi bayo kunye nobunzima.
Ngenxa yobungakanani bayo, i-N6 iya kubonakala inenzuzo ngaphezu kwe-VRC01 kunokuba ikwazi ukujova ngaphantsi, ngaphandle kwe-IV. Ngaphezu koko, ukukwazi ukunyanzelisa phantse yonke inkunkuma ye-HIV kuthetha ukuba ingasetyenziswa njengendlela yokuphatha kunye nokukhusela usulelo.
Nangona umntu efuna ukuthetha nophando ngenqaku lokulumkisa, kwiphepha konke kubonakala kukuthembisa. Isigaba esilandelayo siya kwandisa kwizilwanyana zezilwanyana ezilindelekileyo, mhlawumbi ukuqala ngexesha elithile ekuqaleni kuka-2017.
Okwangoku, iilingo ezimbini zeSigaba II ziqaliswe ukuqala ngo-2017, ukuhlola ukusetyenziswa kwe-VRC01 njengendlela yokukhusela i-HIV (eyaziwa ngokuba yi- HIV ngaphambi kokuba i-prophylaxis, okanye i-PrEP ).
Iimvavanyo zoluntu ezinkulu ziza kugqiba ukuba i-VRC01 ingabonelela ngenzuzo yokukhusela kubantu abangenayo i-HIV. Iyokuqala iya kwenzeka kwiindawo ezingama-24 eBrazil, ePeru, nase-United States, kunye nabhalisa abantu abangama-2,700 nabesigqeba abalala ngesondo nabantu . Owesibini uya kubamba abafazi abangama-1,500 eBotswana, eKenya, eMalawi, eMozambique, eMzantsi Afrika, eTanzania naseZimbabwe.
> Imithombo:
> Ibar, K .; Harrison, L; Overton, E .; okqhubekayo. "ACTG 5340: Impembelelo ye-VRC01 kwiViral Kinetics Emva kokuphazamiseka koPhulo loKhuseleko." INgqungquthela yeeRevrovirus kunye nezifo ezithintekayo (CROI); EBoston, eMassachusetts; NgoFebruwari 22-25, 2016; Inkcazo engabonakaliyo 32LB.
> Chun, T; Sneller, M .; Seamon, C; okqhubekayo. "Impembelelo yoKhuselwa kweNtsholongwane ye-Anti-Veterinary VRC01 kwi-HIV ePlasma Rebound." INgqungquthela yeeRevrovirus kunye nezifo ezithintekayo (CROI); EBoston, eMassachusetts; NgoFebruwari 22-25, 2016; INgqungquthela engama-311LB.
> Eroskin, A .; LeBlanc, A .; Iiveki, D .; okqhubekayo. "I-bNAber: isiseko sedatha ye-antibodies." UPhando lweNucleic Acid. Ja nuwari 2014; 42 (Inkcazelo yeDatabase): D1133-1139.
> I-Network Prevention Trials Network (HPTN). "I-HPTN Studies: Uluhlu Lokufunda - HVTN 704 / HPTN 085 kunye ne-HVTN 703 / HPTN 081." EWashington, DC.
> Huang, J .; Kang, B .; Ishida, E; okqhubekayo. "Ukuchongwa kwe-CD4-Ukukhupha i-Antibody Site kwisandulela-ngculaza eguqule kufuphi ne-Pan neutralization Isinkwa." Ku khuselwa. Novemba 15, 2016; 45 (5): 1108-1121; INGXELO: 10.1016 / j.immuni.2016.10.027.