Imithi Yokugomela Umalaleveva: Ingabe Ubuchwepheshe Okusha Okutholakalayo Kokugomela I-DNA Buzothonya Isifundo Sesikhathi Esizayo?

Ukwakha umuthi wokugomela umalaleveva kube phakathi kwezinselelo ezinkulu ngaphambi kwesayensi. I-Mosquirix^TM , umuthi wokugomela umalaleveva usanda kugunyazwa yi-WHO. Nakuba ukusebenza kwalo mgomo cishe kungama-37%, nokho lesi yisinyathelo esihle esiya phambili njengoba kungokokuqala noma yimuphi umuthi wokugomela umalaleveva ubona usuku. Phakathi kwabanye abazogomela umalaleveva, abakwa DNA imithi yokugoma esebenzisa i-adenovirus njengevektha yokubonisa, okungenzeka ihlinzeke ngama-antigen amaningi kamalaleveva ibonakala inamandla amakhulu njengoba ubuchwepheshe obusetshenzisiwe muva nje bufakazele ukufaneleka kwabo esimweni somgomo we-Oxford/AstraZeneca (ChAdOx1 nCoV-2019) wokugomela i-COVID-19.  

Imithi ngokumelene umalaleveva kube yinselelo ngenxa yomlando wempilo eyinkimbinkimbi ye-parasite ekhombisa izigaba zokukhula ezihlukene, lapho ubamba iqhaza, ukubonakaliswa kwenani elikhulu lamaphrotheni ahlukene ngezigaba ezahlukahlukene, ukuxhumana okuyinkimbinkimbi phakathi kwe-parasite biology kanye ne-host immune, kuhambisana ukuntuleka kwezinsiza ezanele kanye nokuntuleka kokubambisana okuphumelelayo komhlaba wonke ngenxa yokusabalala kwezifo emazweni amaningi omhlaba wesithathu. 

Kodwa-ke, kuye kwenziwa imizamo embalwa yokukhiqiza nokuthuthukisa umuthi wokugomela lesi sifo esiyingozi. Konke lokhu kubhekwa njenge-pre-erythrocytic imijovo yokugoma njengoba zibandakanya iphrotheni ye-sporozoite futhi ihlose i-parasite ngaphambi kokuba ingene kumaseli esibindi. Eyokuqala eyasungulwa kwakuyi-radiation-attenuated IPlasmodium falciparum umgomo we-sporozoite (PfSPZ).¹ lokho bekuzonikeza isivikelo P. falciparum ukutheleleka ku umalaleveva-abantu abadala. Lokhu kwathuthukiswa yi-GSK kanye ne-Walter Reed Army Institute of Research (WRAIR) maphakathi nawo-1970 kodwa ayizange ibone ukukhanya kosuku njengoba kwakungekho ukusebenza okubalulekile kokugoma okubonisiwe. Uhlolo lwakamuva lweSigaba 2 olwenziwa ezinganeni ezingama-336 ezinezinyanga ezi-5-12 ukuze kutholwe ukuphepha, ukubekezelelana, ukungavikeleki komzimba kanye nokusebenza ngempumelelo koMjovo we-PfSPZ ezinganeni ezisanda kuzalwa ekuthelelekeni okuphezulu. umalaleveva ukuhlala entshonalanga yeKenya (I-NCT02687373)², futhi yabonisa imiphumela efanayo ukuthi nakuba kwakukhona ukwanda okuncike kumthamo ezimpendulo ze-antibody ezinyangeni ze-6 kumaqembu we-dose ephansi kakhulu futhi ephakeme kakhulu, izimpendulo ze-T cell zazingabonakali kuwo wonke amaqembu omthamo. Ngenxa yokungabikho kokusebenza okubalulekile komgomo, kunqunywe ukuthi kungalandelwa lo mgomo kuleli qembu lobudala. 

Omunye umgomo owasungulwa yi-GSK kanye ne-WRAIR ngo-1984 umgomo we-RTS,S, obizwa nge-Mosquirix.^TM eqondise kuphrotheni ye-sporozoite futhi ingumgomo wokuqala owenziwe uhlolo lweSigaba sesi-3³ kanye nelokuqala elizohlolwa ezinhlelweni zokugoma ezijwayelekile ezindaweni ezihaqwe umalaleveva. Imiphumela yalolu cwaningo ibonisa ukuthi phakathi kwezingane ezineminyaka engu-5-17 ubudala ezithole imithamo emi-4 yomgomo we-RTS,S, ukusebenza ngempumelelo ngokumelene nomalaleveva kwaba ngama-36% eminyakeni emine yokulandelela. I-RTS,S iqukethe u-R, okubhekisela endaweni ephindayo emaphakathi, i-tandem eyodwa egcinwe kakhulu ephinda i-tetrapeptide NANP, T ibhekisela ku-T-lymphocyte epitopes i-Th4R ne-Th2R. I-peptide ye-RT ehlanganisiwe ihlanganiswe ngofuzo ku-N-terminal ye-Hepatitis B surface antigen (HBsAg), isifunda "S" (Surface). Le RTS ibe isivezwa ngokuhlanganyela kuma-yeast cells ukuze iveze izinhlayiya ezifana negciwane ezibonisa womabili amaprotheni e-sporozoite (isifunda esingu-R esiphindayo esino-T) no-S endaweni yawo. Ingxenye yesibili ethi “S” ivezwa njenge-HBsAg engahlanganisiwe ehlangana ngokuzenzakalelayo engxenyeni ye-RTS, yingakho igama elithi RTS,S.  

Omunye umgomo owakhelwe ukulwa nawo umalaleveva iyona DNA-Umuthi wokugoma osebenzisa abantu i-adenovirus ukuveza iphrotheni ye-sporozoite ne-antigen (i-apical membrane antigen 1)⁴. Izivivinyo zesigaba sesi-2 ziqediwe kubahlanganyeli abangama-82 kusivivinyo selebula evulekile yeSigaba 1-2 esingahleliwe ukuze kuhlolwe Ukuphepha, Immunogenicity, kanye Ukusebenza Kokusebenza kwalo mgomo ku-Health. Umalaleveva-Abadala Abangenalwazi e-US. Ukuzivikela okuphezulu okuyinyumba okufinyelelwe ngokumelene umalaleveva kulandela ukugonywa ngalo mgomo osuselwa ku-adenovirus subunit bekungama-27%.  

Kolunye ucwaningo, i-adenovirus yomuntu yashintshwa yaba i-chimpanzee adenovirus kanye nenye i-antigen, i-TRAP (iphrotheni enamathelayo ehlobene ne-thrombospondin) yahlanganiswa ne-sporozoite protein kanye ne-apical membrane antigen ukuze kuthuthukiswe ukuvikeleka.⁵. Impendulo yomgomo kulo mgomo weyunithi encane ye-antigen yayingama-25% uma iqhathaniswa no -2% emithini yokugoma yamayunithi amabili amancane uma kuqhathaniswa.  

Ucwaningo olungenhla luphakamisa ukuthi ukusetshenziswa kwe DNA i-adenovirus esekelwe multi-subunit imijovo yokugoma ingase ithole ukuvikelwa okungcono (njengoba kushiwo ngenhla) futhi njengoba kunjalo ocwaningweni olukhonjiswe ngomuthi wokugomela wakamuva we-Oxford/AstraZeneca ChAdOx1 nCoV-2019 wokulwa ne-COVID-19 osebenzisa i-adenovirus eyenziwe ngofuzo njengevektha ukuveza amaprotheni e-spike njenge-antigen. Lobu buchwepheshe bungasetshenziselwa ukuveza okuqondiwe kwamaprotheni amaningi ukuze kuqondiswe umalaleveva i-parasite ngaphambi kokuba ingene kumaseli esibindi. Umgomo wamanje ogunyaziwe we-WHO usebenzisa ubuchwepheshe obuhlukile. Nokho, isikhathi sizosho ukuthi siyowuthola nini umuthi wokugomela umalaleveva ongakwazi ukunakekela umthwalo wezifo emazweni ase-Afrika naseNingizimu-Asia ukuze uvumele umhlaba ukuba unqobe lesi sifo esibulalayo. 

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Okubhekwayo:

1. Clyde DF, Most H, McCarthy VC, Vanderberg JP. Ukugonywa komuntu ngokumelene nomalaleveva we-sporozite-induced falciparum. Ngingu-J Med Sci. 1973;266(3):169–77. Iviki 1973/09/01. I-PMID eshicilelwe: 4583408. DOI: https://doi.org/10.1097/00000441-197309000-00002 

2. Oneko, M., Steinhardt, LC, Yego, R. et al. Ukuphepha, ukuzivikela komzimba nokusebenza ngempumelelo komgomo we-PfSPZ wokugomela umalaleveva ezinganeni ezisentshonalanga yeKenya: ukuhlolwa okuphindwe kabili okungaboni kahle, okungahleliwe, okulawulwa yi-placebo okulawulwa yi-placebo. Nat Med 27, 1636-1645 (2021). https://doi.org/10.1038/s41591-021-01470-y 

3. Laurens M., 2019. Umuthi wokugoma i-RTS,S/AS01 (Mosquirix™): uhlolojikelele. Umuntu Imithi kanye ne-Immunotherapeutics. Umqulu 16, 2020 - Ukukhishwa 3. Kushicilelwe ku-inthanethi: 22 Oct 2019. DOI: https://doi.org/10.1080/21645515.2019.1669415 

4. Chuang I., Sedegah M., et al 2013. DNA I-Prime/Adenovirus Boost Boost Malaria Vaccine Encoding P. falciparum I-CSP kanye ne-AMA1 Idala Ukuvikelwa Okuyinyumba Okuhlotshaniswa Nokungavikeleki Okuphakathi Kweseli. I-PLOS eyodwa. Kushicilelwe: February 14, 2013. DOI: https://doi.org/10.1371/journal.pone.0055571 

5. Sklar M., Maiolatesi,S., et al 2021. I-antigen emithathu IPlasmodium falciparum DNA prime—Umuthi wokugomela umalaleveva wokuthuthukisa i-Adenovirus uphakeme kunohlelo lwama-antigen amabili futhi uvikela ekungenweni yisifo sikamalaleveva olawulwayo kubantu abadala abaphilile abangenalwazi umalaleveva. I-PLOS eyodwa. Kushicilelwe: Septhemba 8, 2021. DOI: https://doi.org/10.1371/journal.pone.0256980 

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