iindaba

Ngaphantsi kwesithunzi sobhubhani we-Covid-19, impilo yoluntu yehlabathi ijongene nemiceli mngeni engazange ibonwe ngaphambili. Nangona kunjalo, kukule ngxaki kanye apho inzululwazi kunye neteknoloji zibonise amandla amakhulu kunye namandla. Ukusukela oko kwaqhambuka lo bhubhani, uluntu lwenzululwazi yehlabathi kunye noorhulumente babambisene ngokusondeleyo ukukhuthaza uphuhliso olukhawulezileyo kunye nokukhuthazwa kwezitofu zokugonya, ukufikelela kwiziphumo ezimangalisayo. Nangona kunjalo, imiba efana nokungalingani kokusasazwa kwezitofu zokugonya kunye nokungonelanga koluntu kokulungela ukufumana ugonyo kuseyingxaki kumlo wehlabathi wokulwa nobhubhane.

Phambi kobhubhani we-Covid-19, umkhuhlane we-1918 wawuyeyona nto inamandla yokuqhambuka kwesifo esosulelayo kwimbali yase-US, kwaye inani lokufa elibangelwe ngulo bhubhani we-Covid-19 laliphantse laphinda kabini elo lomkhuhlane we-1918. Ubhubhani we-Covid-19 uqhube inkqubela phambili engaqhelekanga kwicandelo logonyo, ukubonelela ngezitofu ezikhuselekileyo nezisebenzayo kuluntu kunye nokubonisa amandla oluntu lwezonyango ukuphendula ngokukhawuleza kwimingeni emikhulu xa kujongwa iimfuno ezingxamisekileyo zempilo yoluntu. Kumalunga nokuba kukho imeko eethe-ethe kwicandelo logonyo lesizwe kunye nehlabathi jikelele, kubandakanywa nemiba enxulumene nokusasazwa kogonyo kunye nolawulo. Amava esithathu kukuba intsebenziswano phakathi kwamashishini abucala, oorhulumente, kunye nezifundiswa zibalulekile ekukhuthazeni uphuhliso olukhawulezayo lwesitofu sokugonya se-Covid-19 sesizukulwana sokuqala. Ngokusekelwe kwezi zifundo zifundiweyo, i-Biomedical Advanced Research and Development Authority (BARDA) ifuna inkxaso yophuhliso lwesizukulwana esitsha sezitofu eziphuculweyo.

Iprojekthi ye-NextGen linyathelo le-5 yeebhiliyoni zeedola elixhaswa ngemali liSebe lezeMpilo kunye neeNkonzo zoLuntu elijolise ekuphuhliseni isizukulwana esilandelayo sezisombululo zezempilo ze-Covid-19. Esi sicwangciso siza kuxhasa ulingo oluyimfama kabini, olusebenzayo olulawulwayo lweSigaba se-2b ukuvavanya ukhuseleko, ukusebenza kakuhle, kunye nokungakhuseleki kwezitofu zokugonya zovavanyo ngokunxulumene nezitofu zokugonya ezivunyiweyo kuluntu olwahlukeneyo lobuhlanga nobuhlanga. Silindele ukuba la maqonga okugonya asebenze kwezinye izitofu zokugonya izifo ezosulelayo, ezenza ukuba ziphendule ngokukhawuleza kwiingozi zempilo kunye nokhuseleko lwexesha elizayo. Olu vavanyo luya kubandakanya iingqwalasela ezininzi.

Esona siphelo sicetywayo solingo lwezonyango lweSigaba se-2b luphuculo lwesitofu sokusebenza esingaphezulu kwama-30% kwisithuba soqwalaselo seenyanga ezili-12 xa kuthelekiswa nezitofu zokugonya esele zamkelwe. Abaphandi baya kuvavanya ukusebenza kwesitofu sokugonya esitsha ngokusekwe kwisiphumo saso sokukhusela ngokuchasene neempawu ze-Covid-19; Ukongeza, njengesiphelo sesibini, abathathi-nxaxheba baya kuzivavanya ngokwabo ngeempumlo swabs rhoqo ngeveki ukuze bafumane idatha malunga nosulelo olungabonakaliyo. Ugonyo olukhoyo ngoku eUnited States lusekwe kwi-antigens ye-spike yeprotein kwaye ilawulwa ngenaliti ye-intramuscular, ngelixa isizukulwana esilandelayo sogonyo lwabaviwa siya kuxhomekeka kwiqonga elahluke kakhulu, kubandakanya i-spike protein gene kunye nemimandla egcinwe ngakumbi ye-virus genome, efana nejene encoding nucleocapsid, inwebu, okanye ezinye iiprotein ezingakhiwanga. Iqonga elitsha linokubandakanya izitofu zokugonya eziphinda ziphinde zisebenze ezisebenzisa ii-vectors ezine/ezingenakho ukuphinda-phinda kwaye ziqulathe imizila ye-encoding ye-SARS-CoV-2 yesakhiwo kunye neeproteni ezingezizo. Isitofu sokugonya se-mRNA (samRNA) sesizukulwana sesibini luhlobo lwethekhinoloji oluvela ngokukhawuleza olunokuthi luvavanywe njengenye isisombululo. Isitofu sokugonya se-samRNA sifaka ii-replicases ezithwele ulandelelwano olukhethiweyo lwe-immunogenic kwi-lipid nanoparticles ukuqalisa iimpendulo ezichanekileyo zokuzikhusela komzimba. Iingenelo ezinokubakho zeli qonga zibandakanya iidosi ezisezantsi ze-RNA (ezinokunciphisa ukusebenza kwakhona), iimpendulo ze-immune ezihlala ixesha elide, kunye nezitofu ezizinzileyo kumaqondo obushushu efriji.

Inkcazo yokulungelelaniswa kokhuseleko (CoP) yindlela ethile yokuphendula i-humoral kunye ne-cell immune immune enokubonelela ngokukhuseleka kwintsholongwane okanye ukuphinda uhlaziywe nge-pathogens ethile. Ulingo lweSigaba 2b luya kuvavanya ii-CoP ezinokubakho zesitofu sokugonya se-Covid-19. Kwiintsholongwane ezininzi, kubandakanya ii-coronavirus, ukumisela i-CoP ibisoloko ingumngeni kuba amacandelo amaninzi eempendulo zokhuselo lomzimba asebenza kunye ukuze angasebenzi intsholongwane, kubandakanya ne-neutheralizing kunye ne-non neutralizing antibodies (ezifana ne-agglutination antibodies, precipitation antibodies, or complement fixation antibodies), isotype antibodies, CD4 + kunye ne-CD8 + T iiseli, i-antibody Fc effect effect, i-antibody Fc effector. Ngokuntsonkothileyo, indima yala macandelo ekuxhathiseni i-SARS-CoV-2 inokwahluka ngokuxhomekeke kwindawo ye-anatomical (efana nokujikeleza, izicubu, okanye umphezulu wokuphefumla we-mucosal) kunye nesiphelo esiqwalaselwe (njengosulelo lwe-asymptomatic, usulelo oluneempawu, okanye isigulo esiqatha).

Nangona ukuchonga i-CoP kuhlala kungumngeni, iziphumo zolingo lwesitofu sokuvunywa kwangaphambili zinokunceda ukulinganisa ubudlelwane phakathi kokujikeleza amanqanaba e-antibody kunye nokusebenza kogonyo. Chonga izibonelelo ezininzi ze-CoP. I-CoP ebanzi inokwenza amaphononongo okuvala amajoni omzimba kumaqonga amatsha okugonya ngokukhawuleza kwaye angabizi kakhulu kunolingo olukhulu olulawulwa yi-placebo, kwaye incede ekuvavanyeni isakhono sokukhusela sesitofu sokugonya sabantu esingaqukwanga kulingo olusebenzayo lwesitofu, njengabantwana. Ukumisela i-CoP kunokuvavanya ixesha lokugonyeka emva kosulelo ngeentlobo ezintsha okanye ugonyo oluchasene nohlobo olutsha, kunye nokunceda ukufumanisa ukuba zifuneka nini izithonga ze-booster.

Umehluko wokuqala we-Omicron wavela ngoNovemba ka-2021. Xa kuthelekiswa nohlobo lokuqala, malunga ne-30 ye-amino acids endaweni yayo (kuquka i-15 ye-amino acids kwi-spike protein), kwaye ngoko yonyulwa njengenye yenkxalabo. Kubhubhani wangaphambili obangelwe ziintlobo ezininzi ze-COVID-19 ezinje nge-alpha, i-beta, idelta kunye ne-kappa, umsebenzi wokuthamba wee-antibodies oveliswe lusulelo okanye ugonyo oluchasene nokwahluka kwe-Omikjon wancitshiswa, okwenze ukuba i-Omikjon ithathe indawo yentsholongwane ye-delta kwihlabathi jikelele kwiiveki ezimbalwa. Nangona isakhono sokuphindaphinda kwe-Omicron kwiiseli ezisezantsi zokuphefumla sehlile xa kuthelekiswa nobunzima bokuqala, oko kwakhokelela ekonyukeni okubukhali kumazinga osulelo. Ukuzivelela okwalandelayo kokwahluka kwe-Omicron ngokuthe ngcembe kwaphucula ukukwazi kwayo ukuphepha izilwa-buhlungu ezikhoyo, kwaye umsebenzi wayo wokuzibophelela kwi-angiotensin eguqula i-enzyme yesi-2 (ACE2) ii-receptors nazo zanda, ezikhokelela ekonyukeni kwesantya sosulelo. Nangona kunjalo, umthwalo onzima wale miqobo (kubandakanywa ne-JN.1 inzala ye-BA.2.86) iphantsi. Ukunganyangeki kwe-humoral inokuba sisizathu sobuqatha obusezantsi besi sifo xa kuthelekiswa nosulelo lwangaphambili. Ukusinda kwezigulana ze-Covid-19 ezingakhange zivelise izilwa-buhlungu (ezifana nezo zinonyango olubangela ukunqongophala kwe-B-cell) kuqaqambisa ngakumbi ukubaluleka kokugonywa kweeseli.

Olu qwalaselo lubonisa ukuba iiseli ze-T zememori ezikhethekileyo ze-antigen azichatshazelwa kangako lutshintsho lweprotein ye-spike kwiintlobo eziguqukayo xa kuthelekiswa nezilwa-buhlungu. Iiseli zeMemori T zibonakala zikwazi ukuqaphela iiepitopes ze-peptide ezigcinwe kakhulu kwi-spike protein receptor binding domains kunye nezinye ii-viral encoded structural and non-structural proteins. Oku kufunyaniswayo kunokucacisa ukuba kutheni i-mutant strains enovelwano olusezantsi kwi-antibodies ekhoyo engathathi hlangothi inokunxulunyaniswa nesifo esincinci, kwaye ibonise imfuneko yokuphucula ukufunyanwa kwe-T cell-mediated immune response.

Indawo ephezulu yokuphefumla yindawo yokuqala yokunxibelelana kunye nokungena kwiintsholongwane zokuphefumula ezifana ne-coronavirus (i-epithelium yeempumlo ityebile kwi-ACE2 receptors), apho zombini iimpendulo ze-immune ezizalwa kunye neziguqukayo zenzeka. Ugonyo lwangoku olukhoyo lwe-intramuscular lunamandla alinganiselweyo okudala iimpendulo ezinamandla zokuzikhusela kwi-mucosal. Kubemi abanamazinga aphezulu okugonya, ukuxhaphaka okuqhubekayo kohlobo olwahlukileyo kunokusebenzisa uxinzelelo olukhethekileyo kuhlobo olwahlukileyo, okonyusa amathuba okubaleka amajoni omzimba. Ugonyo lwe-Mucosal lunokuvuselela zombini iimpendulo ze-immune zokuphefumla zasekhaya kunye neempendulo zenkqubo yomzimba yokuzikhusela, zithintele usulelo loluntu kwaye zibenze isitofu esifanelekileyo. Ezinye iindlela zokugonywa ziquka i-intradermal (i-microarray patch), ngomlomo (ithebhulethi), i-intranasal (i-spray okanye i-drop), okanye i-inhalation (i-aerosol). Ukuvela kwezitofu zokugonya ezingenanaliti kunokunciphisa ukuthandabuza ngamayeza okugonya kwaye kwandise ukwamkelwa kwawo. Nokuba yeyiphi na indlela ethathiweyo, ukwenza lula ugonyo kuya kunciphisa umthwalo kubasebenzi bezempilo, ngaloo ndlela kuphuculwe ukufikeleleka kwesitofu kunye nokuququzelela amanyathelo okuphendula ubhubhane wexesha elizayo, ngakumbi xa kuyimfuneko ukuphumeza iinkqubo zokugonya ezinkulu. Ukusebenza kogonyo lwedosi enye ye-booster kusetyenziswa i-enteric coated, iipilisi zokugonya ezizinzile zobushushu kunye nezitofu zokugonya ze-intranasal ziya kuvavanywa ngokuvavanya iimpendulo ze-antigen-specific IgA kwi-gastrointestinal kunye namaphecana okuphefumla.

Kwinqanaba lesi-2b lolingo lwezonyango, ukujonga ngononophelo ukhuseleko lomthathi-nxaxheba kubaluleke ngokulinganayo njengokuphucula ukusebenza kwesitofu sokugonya. Siza kuqokelela ngokucwangcisiweyo kwaye sihlalutye idatha yokhuseleko. Nangona ukhuseleko lwezitofu zokugonya i-Covid-19 lubonakaliswe kakuhle, iziphumo ezingalunganga zingenzeka emva kwalo naluphi na ugonyo. Kulingo lwe-NextGen, malunga ne-10000 yabathathi-nxaxheba baya kuhlolwa umngcipheko wokusabela okungalunganga kwaye baya kubelwa ngokungacwangciswanga ukuba bafumane isitofu solingo okanye isitofu sokugonya esinelayisensi kumlinganiselo we-1:1. Uvavanyo olucacileyo lweempembelelo ezimbi zendawo kunye nenkqubo ziya kunika ulwazi olubalulekileyo, kubandakanywa iziganeko zeengxaki ezifana ne-myocarditis okanye i-pericarditis.

Umceli mngeni onzima abajongene nawo abavelisi bamachiza sisidingo sokugcina amandla okuphendula ngokukhawuleza; Abavelisi kufuneka babenakho ukuvelisa amakhulu ezigidi zeedosi zokugonya phakathi kweentsuku ezili-100 zoqhambuko, olukwayinjongo ebekwe ngurhulumente. Njengoko ubhubhani usiba buthathaka kunye nokungenelela kobhubhane kusondela, imfuno yogonyo iya kuncipha kakhulu, kwaye abavelisi baya kujongana nemiceli mngeni enxulumene nokugcina amatyathanga obonelelo, izixhobo ezisisiseko (ii-enzymes, i-lipids, i-buffers, kunye ne-nucleotides), kunye nokuzalisa kunye nokusebenza kwamandla. Okwangoku, imfuno yogonyo lwe-Covid-19 kuluntu isezantsi kunemfuno ngo-2021, kodwa iinkqubo zemveliso ezisebenza kwisikali esincinci "kubhubhane olupheleleyo" zisafuna ukuqinisekiswa ngabasemagunyeni. Uphuhliso oluthe kratya lweklinikhi lukwafuna ukuqinisekiswa kwabasemagunyeni abalawulayo, abanokubandakanya izifundo zokungaguquguquki phakathi kweebhetshi kunye nezicwangciso ezilandelayo zeSigaba sesi-3 sokusebenza ngempumelelo. Ukuba iziphumo zolingo olucwangcisiweyo lweSigaba se-2b zinethemba, kuya kunciphisa kakhulu imingcipheko enxulumeneyo yokuqhuba ulingo lweSigaba sesi-3 kwaye ivuselele utyalo-mali lwabucala kulingo olunjalo, ngaloo ndlela ibenakho ukuphumeza uphuhliso lorhwebo.

Ubude bexesha lokuphela kobhubhane alukakaziwa, kodwa amava akutsha nje abonisa ukuba eli xesha alifanele lichithwe. Eli xesha lisinike ithuba lokwandisa ukuqonda kwabantu ngesitofu sokugonya kunye nokwakha kwakhona ukuthembana nokuzithemba kwizitofu zokugonya kubantu abaninzi kangangoko.