Ebhekene nezingqinamba ekuthuthukiseni umuthi wokugoma wegciwane lesandulela ngculazi , ososayensi baye bagxilisa kakhulu eminyakeni yamuva ekutholeni izindlela zokuzivikela ezivela emvelo ezingasiza umzimba ukulwa noma ukuvimbela, ukutheleleka nge-HIV.
Ubufakazi bale ndlela buqinile. Sisazi, isibonelo, ukuthi kukhona i-subset yabantu abathiwa abalawuli abakhulu ababonakala bakwazi ukulawula i-HIV ngaphandle kokusebenzisa izidakamizwa.
Lapho sibhekisisa laba bantu, abacwaningi baye bakwazi ukuhlukanisa izici eziningana ezihlobene nalokhu kuvikelwa kwemvelo.
Phakathi kwalezi zihlobo zamaprotheni omzimba omzimba okuthiwa ama-antibodies ajwayelekile (neBNAbs) , okuvame ukubonwa kubalawuli abakhulu futhi, ngokungafani nama-antibodies "ajwayelekile," akwazi ukunciphisa ukuhlukahluka okuhlukahlukene kwezifo ze-HIV .
Ngo-November 2016, ososayensi abanezikhungo zikazwelonke zezeMpilo bamemezela ukutholakala kwe-bNAb entsha, ebizwa nge-N6, eyakwazi ukunciphisa amaphesenti angu-98 azo zonke izinkinga ze-HIV emilenzeni ye-pre-clinic. Le nsizakalo ye-immune inoveli, ehlukaniswe ne-HIV elite control, kuthiwa iphumelele izikhathi ezingu-10 ekubulaweni kwegciwane lesandulela ngculaza kunanoma yiliphi elinye i-bNAb elaziwa manje.
Ukuqonda Ngokubanzi Ukunciphisa Ama-antibodies
Ama-antibodies ayenama-proteins anomumo we-Y akhiqizwa amasosha omzimba ukusiza ukulwa nezifo ezibangelwa isifo njengama-bacteria noma ama-virus.
Ngokuvamile, iningi lihlelwe ukulwa nohlobo olulodwa lwe-pathogen kanye ne-pathogen eyodwa yodwa-isimo esibucayi esinikezwa ukuthi i- HIV iguqule njalo futhi ikwazi ukuthola ukutholakala kalula ngokungazi ukuthi i-antibody evikelayo.
Ngokuphambene nalokho, i-bNAbs iyakwazi ukulandelela i-HIV ngisho nalapho ihlaziya futhi iguquguquka, ihlonza igciwane hhayi nge-conformation yayo yesakhiwo kodwa yi-receptors ebusweni begciwane (okubizwa ngokuthi amasayithi okubopha i-CD4), okungeke kube lula ukuguqula.
Ngenkathi ama-bNAb ejwayele ukuhlanganiswa nokulawulwa kwe-elite, empeleni, azokhula kubo bonke abantu abanesandulela ngculaza, nakuba behamba kancane kakhulu.
Kwabalawuli abaningi abakhulu, ukutholakala kwama-bBab kubhekwe njengengqondo, okusho ukuthi bakhona ngesikhathi sokutheleleka. Kubanikazi be-non-elite, i-bNAbs izovame ukuvela phakathi neminyaka engu-2-3 yokutheleleka kokuqala, ngesikhathi lapho igciwane lizozifaka khona emasethini nasezicukweni ezibizwa ngokuthi izibhamu ezivaliwe , lapho kuzohlala zifihliwe ekutholakaleni kwe-immune.
Ososayensi manje bakholelwa ukuthi uma bengakhuthaza amasosha omzimba ukuba akhiqize ama-bBab "ngokufunwa," angakwazi ukuvimbela ukutheleleka noma ukunciphisa inkinga yesifo, ngaphandle noma ngaphandle kwemithi.
Umlando Wezemvelo Wokunciphisa Ngokukhululekile Ama-antibodies
Ngenkathi ososayensi beqala ukuqala ukubona ama-bNAbs ekuqaleni kwawo-1990, kwaba ngo-2009 kuphela ukuthi abaningana abaphumelele kakhulu abaqokonyayo baqaphele abacwaningi begciwane. Phakathi kwazo kwakuyi-VRC01, i-bNAb eyayingasondelene nomuntu wase-Afrika waseMelika futhi kamuva yaboniswa ukunciphisa amaphesenti angu-90 azo zonke izinhlobo ze-HIV-1.
I-VRC01 isebenza ngokunamathisela kwisayithi yokubopha i-CD4 ebusweni begciwane, ukuvimbela i-HIV ukuba ingene esitokisini esasengozini.
Ukuhlolwa kwezilwane zakuqala ukuphenya i-VRC01 kubonise isithembiso, kanye nezilwane ezinjengezilwane ezijova ngezifo ezithi zibonisa ukulawulwa kwegciwane isikhathi esingangezinyanga eziyisithupha.
Ukuhlolwa komuntu, ngokuphambene, kuye kwadumaza kakhulu. Ucwaningo olwenziwa ngo-2016 oluvela ku-AIDS Clinical Trial Group lubonise ukuthi izifo ezithintekayo ze-VRC01, ngenkathi zibekezeleleke kahle, azenzele kancane ukulawula isandulela ngculazi kulabo ababambiqhaza ababekhipha izidakamizwa zabo. Izijovo eziningi azikwazanga ukuthuthukisa kule miphumela.
Ukutholakala kwe-N6 antibody entsha kubhekwa kubalulekile phakathi kwalabo abayibona umlandeli wemvelo ku-VRC01, kokubili ekuzalweni kofuzo kanye ne-potency.
Futhi kukhona ubufakazi obuqinile bokusekela le mibono.
Ngaphambilini kuya ku-N6, iningi lezinkampani ze-BNAb libe likhulu kakhulu kodwa lisezingeni eliphansi (njengalokhu liyi-VRC01) noma likhulu kakhulu kodwa lincane kakhulu. I-N6 ivela, okungenani ezivivinyweni zangaphambi komtholampilo, ukuze iphumelele kuzo zombili izingxenyana, ihlukumeze u-98% wezinkinga ezingu-181 ze-HIV ezihlukene (kufaka phakathi imithi engu-16 kwezingu-20 ezikhunjulwa kwamanye amagciwane ku-bNAB ekilasini layo).
Ukuphumelela okukhulu kungathiwa isakhiwo esingavamile sika-antibody, esivumela ukuba sigweme ama-carbohydrate "eminyango yeminyango" evimbela amanye ama-bNAbs ekufakeni igciwane.
Ingabe i-N6 izovula i-Doorway eya kwi-HIV Cure?
Kufanele i-N6 ikwazi ukufeza imiphumela efanayo emilenzeni yabantu, kungaba yileli qembu lokuqala lokukhokhela ukuhlukahluka kwegciwane lesandulela ngculaza, kokubili ezingeni labantu ngabanye kanye nendawo.
Lokhu akusho ukuthi ngeke kushaye izithiyo ezifanayo ezibonwa yizilingo zokuqala ze-VRC01, lapho inoculation eqondile ehlulekile ukuphindaphinda izinzuzo zokulawulwa kwabantu abakhulu. Ngokufanayo, kukhona ubufakazi obuncane bokusikisela ukuthi singenza ukuba amasosha omzimba akhiqize lezi zinselo zomzimba, okungenani ngokwanele okwanele okubhekwa njengesivikelo.
Enye yezinselelo ezinkulu ababhekene nazo abacwaningi ukuthi ukufakwa kwe-bNAb eyodwa kubonakele kanzima kakhulu. Ngokuvamile, lapho ososayensi bezama ukufaka impendulo, umzimba uzophendula ngempendulo ephikisanayo, ephumelela ekunciphiseni umphumela. Ngokuyinhloko yindlela yomzimba yokubeka "ama-brake" ohlelweni lokuzivikela omzimba ukuqinisekisa ukuthi alusebenzi kahle (njengoba kwenzeke ngezifo ezizimele ) noma kungasebenzi (njengoba kwenzeke ngokuphazamiseka kwe-immune suppression).
Izindaba eziyinkimbinkimbi eziqhubekayo yizindawo zokugcina eziphephile lapho i-HIV ingahlala ivikelekile ekutholeni iminyaka nemashumi eminyaka. Inkinga yilezi: igciwane lesandulela ngculaza kuphela lingasetshenziswa yi-bNAbs; lezo ezifihliwe kude emagodini amaselula azikwazi. Kuwukuthi "ukukhahla" i-HIV ngaphandle kokufihla ukuthi ama-bBabane anethuba lokwenza umuthi wokugcina unomphela. Isu le-multi-pronged, eyaziwa ngokuthi "ukubulala," namuhla libhekwa njengento yokuqala phakathi kwamaqembu okucwaninga nge-HIV.
Ikusasa le-BNAb Research
Kungakhathaliseki ukuthi ososayensi banganqoba noma iyiphi yalezi zithiyo akukaze kubonwe. Lokho esikwaziyo ngokuqinisekile ukuthi i-N6 idlulele kunoma yiziphi ezinye i-bNAbs okwamanje eziphenywayo, kokubili ngobubanzi bayo nobukhulu bezinkinga.
Ngenxa yobungako bayo, i-N6 izobonakala inenzuzo ngaphezu kwe-VRC01 uma ingakwazi ukujovwa ngaphansi kwesigqila, kunokuba i-IV. Ngaphezu kwalokho, ikhono layo lokunciphisa cishe zonke izinkinga ze-HIV lisho ukuthi lingasebenzisa njengendlela yokuphatha nokuvimbela ukutheleleka kokubili.
Ngenkathi umuntu efuna ukusondela ocwaningweni ngombhalo wokuqapha, ephepheni konke kubonakala kunethemba. Isigaba esilandelayo sizokhula kuze kuvivinywe izilwane zezilwane, okungenzeka ziqale esikhathini esithile ekuqaleni kuka-2017.
Phakathi naleso sikhathi, izivivinyo ezimbili zeSigaba II zizoqala ngo-2017, zihlolisise ukusetshenziswa kweVRC01 njengendlela yokuvimbela i-HIV (eyaziwa ngokuthi yi- HIV pre-exposure prophylaxis, noma i-PrEP ).
Izilingo zabantu ezinkulu zizonquma ukuthi i-VRC01 ingahlinzeka yini inzuzo yokuzivikela phakathi kwabantu abangegciwane lesandulela ngculaza, enikezwe ama-infusions amabili. Iyokuqala izokwenzeka ezindaweni ezingu-24 eBrazil, ePeru nase-United States, ngokubhaliswa kwabangu-2 700 nabesilisa abathandana abalala nobulili namadoda . Owesibili uzothola abesifazane abangu-1 500 eBotswana, Kenya, eMalawi, eMozambique, eNingizimu Afrika, eTanzania naseZimbabwe.
> Imithombo:
> Ibha, K .; UHarrison, uL .; I-Overton, i-E .; et al. "ACTG 5340: Umphumela we-VRC01 ku-Viral Kinetics Ngemuva kokuphazamiseka kwe-Analytic Treatment." Ingqungquthela yama-Retroviruses kanye nezifo ezithinta amathuba (CROI); IBoston, eMassachusetts; Februwari 22-25, 2016; I-Conference abstract 32LB.
> Chun, T .; I-Sneller, M .; Seamon, C .; et al. "Umthelela wokukhushulwa kwe-Antibody VRC01 ngokubanzi ku-HIV Plasma Rebound." Ingqungquthela yama-Retroviruses kanye nezifo ezithinta amathuba (CROI); IBoston, eMassachusetts; Februwari 22-25, 2016; I-Conference abstract 311LB.
> Eroskin, A .; I-LeBlanc, A .; Amaviki, D .; et al. "I-bNAber: i-database ye-antibodies ephelele." Ucwaningo lwe-Nucleic Acid. Januwari 2014; 42 (Issue Issue): D1133-1139.
> I-Network Prevention Trials Network (HPTN). "I-HPTN Studies: Uhlu Lokufundwa - HVTN 704 / HPTN 085 ne-HVTN 703 / HPTN 081." Washington, DC.
> Huang, J .; Kang, B .; Ishida, E .; et al. "Ukukhomba i-Anti-Anti-Anti-Anti-Site Site Anti-HIV eguqule eduze kwe-Pan Neutralization Isinkwa." Ukungakhulelwe. NgoNovemba 15, 2016; 45 (5): 1108-1121; I-DOI: 10.1016 / j.immuni.2016.10.027.