izindaba

Ngaphansi komthunzi womqedazwe we-Covid-19, ezempilo zomphakathi emhlabeni wonke zibhekene nezinselelo ezingakaze zibonwe ngaphambili. Kodwa-ke, kukuleso simo esibucayi lapho isayensi nobuchwepheshe bubonise khona amandla namandla abo amakhulu. Kusukela kwaqubuka lolu bhubhane, umphakathi wesayensi yomhlaba wonke kanye nohulumeni babambisane kakhulu ukukhuthaza ukuthuthukiswa okusheshayo nokukhuthazwa kwemithi yokugoma, ukuzuza imiphumela emangalisayo. Kodwa-ke, izingqinamba ezinjengokusatshalaliswa ngokungalingani kwemithi yokugoma kanye nokuzimisela okwanele komphakathi ukuthola imigomo zisahlupha impi yomhlaba wonke yokulwa nalolu bhubhane.

Ngaphambi kobhubhane lwe-Covid-19, umkhuhlane wango-1918 wawuyisifo esithathelwanayo esibi kakhulu emlandweni wase-US, futhi inani lokufa elibangelwe yilolu bhubhane lwe-Covid-19 lalicishe liphindwe kabili kunelomkhuhlane wango-1918. Umqedazwe we-Covid-19 uqhubezele inqubekela phambili emangalisayo emkhakheni wemithi yokugoma, ukuhlinzeka ngemithi yokugoma ephephile nesebenzayo kubantu kanye nokubonisa ikhono lomphakathi wezokwelapha lokuphendula ngokushesha ezinseleleni ezinkulu lapho ubhekene nezidingo eziphuthumayo zezempilo zomphakathi. Kumayelana nokuthi kunesimo esintekenteke emkhakheni wokugoma kazwelonke nowomhlaba wonke, okuhlanganisa nezindaba ezihlobene nokusatshalaliswa komgomo nokuphatha. Okuhlangenwe nakho kwesithathu ukuthi ubudlelwano phakathi kwamabhizinisi azimele, ohulumeni, kanye nezifundiswa kubalulekile ekukhuthazeni ukuthuthuka okusheshayo komgomo wesizukulwane sokuqala we-Covid-19. Ngokusekelwe kulezi zifundo ezitholiwe, i-Biomedical Advanced Research and Development Authority (BARDA) ifuna ukusekelwa ukuze kuthuthukiswe isizukulwane esisha semithi yokugoma ethuthukisiwe.

Iphrojekthi ye-NextGen iwuhlelo lwama-dollar ayizigidi eziyizinkulungwane ezinhlanu oluxhaswe nguMnyango Wezempilo Nezinsizakalo Zabantu okuhloswe ngaso ukuthuthukisa isizukulwane esilandelayo sezixazululo zokunakekelwa kwezempilo kwe-Covid-19. Lolu hlelo luzosekela izivivinyo ezingaboni kabili, ezisebenzayo zeSigaba 2b ukuze kuhlolwe ukuphepha, ukusebenza kahle, kanye nokuvikeleka kwamasosha omzimba kwemithi yokugoma yokuhlola ehlobene nemithi yokugoma egunyaziwe kubantu bezinhlanga ezahlukene nobuhlanga. Silindele ukuthi lezi nkundla zokugoma zisebenze kweminye imigomo yezifo ezithathelwanayo, ibenze bakwazi ukuphendula ngokushesha ezinsongweni zempilo nezokuphepha ezizayo. Lokhu kuhlolwa kuzobandakanya ukucatshangelwa okuningi.

Isiphetho esiyinhloko sohlolo lomtholampilo oluhlongozwayo lweSigaba 2b ukuthuthukisa ukusebenza ngempumelelo komuthi okungaphezu kwama-30% esikhathini esiyizinyanga eziyi-12 sokubhekwa uma kuqhathaniswa nemithi yokugoma esivele igunyaziwe. Abacwaningi bazohlola ukusebenza komgomo omusha ngokusekelwe emthelela wawo wokuvikela ngokumelene ne-Covid-19 enezimpawu; Ukwengeza, njengesiphetho sesibili, ababambiqhaza bazozihlola ngokwabo ngama-nasal swabs masonto onke ukuze bathole idatha ngezifo ezingenazimpawu. Imithi yokugoma etholakala e-United States njengamanje isuselwe kuma-antigen amaprotheni e-spike futhi inikezwe ngomjovo we-intramuscular, kuyilapho isizukulwane esilandelayo semithi yokugoma izoncika endaweni ehluke kakhulu, okuhlanganisa izakhi zamaprotheni e-spike kanye nezifunda ezigcinwe kakhulu ze-genome yegciwane, njengezakhi zofuzo ezifaka ikhodi ye-nucleocapsid, ulwelwesi, noma amanye amaprotheni angahlelekile. Inkundla entsha ingase ihlanganise imithi yokugomela i-viral vector esebenzisa kabusha esebenzisa ama-vector anamandla/angenawo amandla okuphindaphinda futhi aqukathe izakhi zofuzo ezifaka ikhodi ye-SARS-CoV-2 amaprotheni esakhiwo nangenawo isakhiwo. Umuthi wokugomela wesizukulwane sesibili ozikhulisayo we-mRNA (samRNA) uyifomu lobuchwepheshe elivela ngokushesha elingahlolwa njengenye isixazululo. Umuthi wokugoma we-samRNA uhlanganisa izimpinda ezithwala ukulandelana okukhethiwe kwe-immunogenic kuma-lipid nanoparticles ukuze kuqalise ukusabela okunembile kokuzivikela komzimba. Izinzuzo ezingaba khona zale nkundla zifaka imithamo ephansi ye-RNA (enganciphisa ukusebenza kabusha), izimpendulo ezihlala isikhathi eside zokuzivikela komzimba, kanye nemithi yokugoma ezinzile emazingeni okushisa esiqandisi.

Incazelo yokuhlobana kokuvikela (CoP) iyimpendulo ethile eguquguqukayo ye-humoral kanye neselula enganikeza ukuvikeleka ekuthelelekeni noma ekuthelelekeni kabusha ngamagciwane athile. Uhlolo lweSigaba 2b luzohlola ama-CoP angaba khona omgomo we-Covid-19. Kumagciwane amaningi, okuhlanganisa nama-coronavirus, ukunquma i-CoP bekuhlale kuyinselele ngoba izingxenye eziningi zokuphendula kwamasosha omzimba zisebenza ndawonye ukuze zenze igciwane lingasebenzi, okuhlanganisa amasosha omzimba angathathi hlangothi (njengama-agglutination antibodies, precipitation antibodies, or complement fixation antibodies), amasosha omzimba e-isotype, amaseli e-CD4+ kanye ne-CD8+T, ukusebenza kwamaseli e-antibody Fc kanye nomphumela wenkumbulo. Ngokuyinkimbinkimbi ngokwengeziwe, indima yalezi zingxenye ekumelaneni ne-SARS-CoV-2 ingahluka ngokuya ngesizinda se-anatomical (njengokujikeleza, izicubu, noma indawo yokuphefumula ye-mucosal) kanye nesiphetho esicatshangelwayo (njengokutheleleka nge-asymptomatic, ukutheleleka okuyizimpawu, noma ukugula okunzima).

Nakuba ukuhlonza i-CoP kuhlala kuyinselele, imiphumela yokuhlolwa kokugoma kokugunyazwa kusengaphambili ingasiza ekulinganiseni ubudlelwano phakathi kokujikeleza kwamazinga amasosha omzimba angasebenzi kanye nempumelelo yomgomo. Khomba izinzuzo ezimbalwa ze-CoP. I-CoP ebanzi ingase yenze izifundo zokuvala amasosha omzimba ezinkundleni zomuthi wokugoma zisheshe futhi zibe nezindleko ezingaphezulu kunezinhlolo ezinkulu ezilawulwa yi-placebo, futhi isize ukuhlola amandla okuvikela umgomo wabantu abangabandakanyiwe ekuhlolweni kokusebenza komgomo, njengabantwana. Ukunquma i-CoP kungase futhi kuhlole ubude besikhathi sokuzivikela komzimba ngemva kokutheleleka ngezinhlobo ezintsha noma ukugonyelwa izinhlobo ezintsha, futhi kusize ukunquma ukuthi isibhamu esikhuthazayo sidingeka nini.

Okuhlukile kokuqala kwe-Omicron kwavela ngoNovemba 2021. Uma kuqhathaniswa nohlobo lwangempela, inama-amino acid acishe abe ngu-30 ashintshiwe (kuhlanganise nama-amino acid angu-15 kuphrotheni ye-spike), futhi ngenxa yalokho akhethwa njengokuhlukile kokukhathazeka. Kubhubhane lwangaphambilini oludalwe ukuhlukahluka kwe-COVID-19 okuningi okufana ne-alpha, i-beta, i-delta ne-kappa, umsebenzi wokwenza amandla wamasosha omzimba akhiqizwa ukutheleleka noma ukugonyelwa okuhlukile kwe-Omikjon wehlisiwe, okwenze u-Omikjon wathatha indawo yegciwane le-delta emhlabeni wonke phakathi namasonto ambalwa. Nakuba ikhono lokuphindaphinda le-Omicron kumangqamuzana okuphefumula aphansi lehlile uma liqhathaniswa nezinkinga zakuqala, liholele ekwenyukeni okukhulu kwamazinga okutheleleka. Ukuvela okulandelayo kokuhluka kwe-Omicron kancane kancane kwathuthukisa amandla ako okubalekela amasosha omzimba akhona, futhi umsebenzi wawo wokubopha i-angiotensin eguqula i-enzyme 2 (ACE2) receptors nawo anda, okuholela ekwenyukeni kwezinga lokudlulisela. Kodwa-ke, umthwalo onzima walezi zinkinga (kuhlanganise ne-JN.1 inzalo ye-BA.2.86) iphansi kakhulu. Ukungavikeleki okungeyona i-humoral kungase kube isizathu sobunzima obuphansi besifo uma kuqhathaniswa nokudluliselwa kwangaphambilini. Ukusinda kweziguli ze-Covid-19 ezingazange zikhiqize amasosha omzimba anciphisa amandla (njengalawo anokuntuleka kokwelashwa okubangelwa ukushoda kwe-B-cell) kuphinde kugqamise ukubaluleka kokungavikeleki kwamaselula.

Lokhu kubheka kukhombisa ukuthi amaseli e-T enkumbulo eqondene ne-antigen awathinteki kangako ekuguqulweni kokuguqulwa kwamaprotheni e-spike kuma-mutant strains uma kuqhathaniswa namasosha omzimba. Amaseli e-Memory T abonakala ekwazi ukubona ama-epitopes e-peptide agcinwe kakhulu ezizindeni ezibophezela ama-receptor e-spike kanye namanye amaprotheni afakwe ikhodi ye-viral nesakhiwo nangewona wesakhiwo. Lokhu kutholakala kungase kuchaze ukuthi kungani izinhlobo eziguquguqukayo ezinokuzwela okuphansi kumasosha omzimba angathathi hlangothi kungase kuhlotshaniswe nesifo esithambile, futhi kubonise isidingo sokuthuthukisa ukutholwa kwe-T cell-mediated immune response.

Ipheshana lokuphefumula eliphezulu liyindawo yokuqala yokuxhumana kanye nokungena kwamagciwane okuphefumula anjengama-coronavirus (i-epithelium yamakhala inothe ngama-receptors e-ACE2), lapho kuvela khona zombili izimpendulo zokuzivikela ezizalwa nazo neziguquguqukayo. Imithi yokugoma etholakalayo manje ye-intramuscular inamandla alinganiselwe okudala izimpendulo eziqinile zokuzivikela ku-mucosal. Kubantu abanamazinga aphezulu okugoma, ukwanda okuqhubekayo kohlobo oluthile kungase kufake ingcindezi ehlukahlukene, okwandisa amathuba okuba amasosha omzimba aphunyuke. Imithi yokugomela i-mucosal ingashukumisa kokubili ukuphendula kwamasosha omzimba wendawo yokuphefumula kanye nezimpendulo zamasosha omzimba, inciphise ukudluliswa komphakathi futhi iwenze umuthi wokugoma ofanelekile. Eminye imizila yokugoma ihlanganisa i-intradermal (i-microarray patch), ngomlomo (ithebhulethi), intranasal (spray noma drop), noma i-inhalation (i-aerosol). Ukuvela kwemithi yokugoma engenanaliti kungase kunciphise ukungabaza emithini yokugoma futhi kwandise ukwamukeleka kwayo. Kungakhathalekile ukuthi iyiphi indlela ethathwayo, ukugoma kube lula kuzonciphisa umthwalo kubasebenzi bezokunakekelwa kwempilo, ngaleyo ndlela kuthuthukiswe ukufinyeleleka komgomo futhi kube lula izindlela zokubhekana nobhubhane lwesikhathi esizayo, ikakhulukazi uma kudingekile ukuqalisa izinhlelo zokugoma ezinkulu. Ukusebenza kwemithi yokugomela umthamo owodwa kusetshenziswa amaphilisi okugoma aqinile, izinga lokushisa kanye nemithi yokugoma engaphakathi kwamakhala kuzohlolwa ngokuhlola izimpendulo ze-IgA eqondene ne-antigen ethile emapheshaneni amathumbu nasokuphefumula.

Ezivivinyweni zomtholampilo zesigaba 2b, ukuqapha ngokucophelela ukuphepha kwabahlanganyeli kubaluleke ngokufanayo njengokuthuthukisa ukusebenza komgomo. Sizoqoqa ngokuhlelekile futhi sihlaziye idatha yezokuvikela. Yize ukuphepha kwemithi yokugomela i-Covid-19 kufakazelwe kahle, ukusabela okungekuhle kungenzeka ngemuva kwanoma yikuphi ukugoma. Ocwaningweni lwe-NextGen, ababambiqhaza abangaba ngu-10000 bazohlolwa ubungozi bokusabela futhi bazokwabelwa ngezikhathi ezithile ukuze bathole umuthi wokugoma wokuhlola noma umuthi wokugoma onelayisensi ngokwesilinganiso esingu-1:1. Ukuhlolwa okuningiliziwe kokusabela okungalungile kwendawo kanye nesistimu kuzohlinzeka ngolwazi olubalulekile, okuhlanganisa izehlakalo zezinkinga ezifana ne-myocarditis noma i-pericarditis.

Inselele enkulu abakhiqizi bemithi yokugoma ababhekene nayo yisidingo sokugcina amandla okuphendula ngokushesha; Abakhiqizi kumele bakwazi ukukhiqiza amakhulu ezigidi zemithamo yokugoma zingakapheli izinsuku eziyi-100 kubheduke lesi sifo, okuphinde kube umgomo obekwe uhulumeni. Njengoba ubhubhane luba buthaka futhi kusondela isikhathi sokunqamuka kobhubhane, isidingo sokugoma sizokwehla kakhulu, futhi abakhiqizi bazobhekana nezinselelo ezihlobene nokugcina amaketanga okuhlinzeka, izinto eziyisisekelo (ama-enzyme, ama-lipids, ama-buffers, nama-nucleotide), kanye namandla okugcwalisa nokucubungula. Njengamanje, isidingo semithi yokugomela i-Covid-19 emphakathini siphansi kunesidingo sango-2021, kodwa izinqubo zokukhiqiza ezisebenza ngesilinganiso esincane "kunobhubhane olugcwele" zisadinga ukuqinisekiswa yiziphathimandla ezilawulayo. Okunye ukuthuthukiswa komtholampilo nakho kudinga ukuqinisekiswa okuvela kwabaphathi, okungase kuhlanganise izifundo zokuvumelana kwenqwaba kanye nezinhlelo zokusebenza ezisebenzayo zeSigaba sesi-3 ezilandelayo. Uma imiphumela yohlolo oluhleliwe lweSigaba 2b inethemba, kuzonciphisa kakhulu ubungozi obuhlobene bokwenza izivivinyo zeSigaba 3 futhi kugqugquzele ukutshalwa kwezimali kwangasese kulokho kuhlola, ngaleyo ndlela kube namandla okuzuza ukuthuthukiswa kwezohwebo.

Ubude besikhathi sokunqamuka kwamanje kobhubhane akukaziwa, kodwa ulwazi lwakamuva lusikisela ukuthi lesi sikhathi akufanele simoshwe. Lesi sikhathi sisinikeze ithuba lokwandisa ukuqonda kwabantu ngomgomo wokugoma futhi sakhe kabusha ukwethenjwa nokuqiniseka emithini yokugoma kubantu abaningi ngangokunokwenzeka.