Amachiza okugonya isifo seengcongconi: Ngaba iTekhnoloji yoGonyo lweDNA eNtsha eFumanayo iya kuba nefuthe kwisifundo sexesha elizayo?

Ukuphuhlisa isitofu sokugonya isifo seengcongconi kube phakathi kweyona mingeni mikhulu phambi kwenzululwazi. Mosquirix^TM , iyeza lokugonya isifo seengcongconi lisanda kuvunywa yi-WHO. Nangona ukusebenza kwesi sitofu sokugonya kumalunga nama-37%, kodwa eli linyathelo elikhulu ukuya phambili njengoko sisihlandlo sokuqala nasiphi na isitofu sokugonya isifo seengcongconi sibona usuku. Phakathi kwabanye abaviwa isitofu sokugonya isifo seengcongconi, i DNA izitofu zokugonya ezisebenzisa i-adenovirus njengesixhobo sokubonisa, esinokubanakho ukubonelela ngee-antigens zemalariya ezininzi zibonakala zinesakhono esikhulu njengoko itekhnoloji esetyenzisiweyo isandula ukubonisa ukufaneleka kwayo kwimeko yesitofu sokugonya i-Oxford/AstraZeneca (ChAdOx1 nCoV-2019) ngokuchasene ne-COVID-19.  

Iigonya chasene malariya Ibonakalise ukuba ngumceli mngeni ngenxa yembali yobomi entsonkothileyo yesimfimfithi ebonisa amanqanaba ophuhliso ahlukeneyo apho kulo mkhosi, ukubonakaliswa kwenani elikhulu leeprotheyini ezahlukeneyo ngokwamanqanaba ahlukeneyo, ukudibana okuntsonkothileyo phakathi kwebhayoloji yeparasite kunye nokugonyeka komkhosi, kukhatshwa ukunqongophala kwemithombo yoncedo eyaneleyo kunye nokungabikho kwentsebenziswano esebenzayo yehlabathi ngenxa yokuxhaphaka kwezifo kumazwe amaninzi ehlabathi lesithathu. 

Nangona kunjalo, iinzame ezimbalwa zenziwe ukuvelisa kunye nokuphuhlisa isitofu sokugonya esisebenzayo ngokuchasene nesi sifo soyikekayo. Zonke ezi zichazwe njenge-pre-erythrocytic zokugonya njengoko zibandakanya iprotheni ye-sporozoite kwaye ijolise kwi-parasite ngaphambi kokuba ingene kwiiseli zesibindi. Owokuqala ukuphuhlisa yayiyi-radiation-attenuated IPlasmodium falciparum isitofu sokugonya i-sporozoite (PfSPZ).¹ oko kuya kubonelela ngokhuseleko P. falciparum usulelo kwi malariya-abantu abadala. Oku kwaphuhliswa yi-GSK kunye ne-Walter Reed Army Institute of Research (WRAIR) phakathi kwe-1970s kodwa ayizange ibone ukukhanya kwemini njengoko kwakungekho isitofu esibalulekileyo esibonakalisiweyo. Izilingo zeSigaba se-2 zamva nje eziqhutywe kwiintsana ezingama-336 ezineminyaka eyi-5-12 iinyanga ukumisela ukhuseleko, ukunyamezela, ukugonywa kunye nokusebenza kakuhle kwe-PfSPZ Vaccine kwiintsana ekusulelekeni okuphezulu. malariya ukuhlala kwintshona yeKenya (NCT02687373)², Kwakhona wabonisa iziphumo ezifanayo ukuba nangona kukho ukunyuka okuxhomekeke kwi-dose kwiimpendulo ze-antibody kwiinyanga ze-6 kumaqela aphantsi kunye nawona aphezulu, iimpendulo zeeseli ze-T zazingabonakali kuwo onke amaqela edosi. Ngenxa yokungabikho kokusebenza okubalulekileyo kwesitofu sokugonya, kwagqitywa ekubeni singalandelwa sesi sitofu kweli qela lobudala. 

Olunye ugonyo olwaphuhliswa yi-GSK kunye ne-WRAIR ngo-1984 sisitofu se-RTS, S, esibizwa ngokuba yi-Mosquirix.^TM ejolise kwiprotein ye-sporozoite kwaye sisitofu sokuqala esiye safumana ulingo lweSigaba sesi-3³ kunye neyokuqala ukuba ivavanywe kwiinkqubo zogonyo lwesiqhelo kwiindawo ezigquba isifo seengcongconi. Iziphumo zolu lingo zibonisa ukuba phakathi kwabantwana ababudala buphakathi kweenyanga ezi-5-17 abafumene iidosi ezi-4 zesitofu sokugonya i-RTS,S, ukusebenza ngempumelelo kwimalariya kuma-36% kwiminyaka emi-4 yokulandela. I-RTS,S iqulethe i-R, ebhekiselele kummandla ophindayo osembindini, i-tandem eyodwa egcinwe kakhulu iphinda i-tetrapeptide NANP, i-T ibhekisa kwi-T-lymphocyte epitopes i-Th2R ne-Th3R. I-peptide ye-RT edibeneyo ixutywe ngofuzo kwi-N-terminal ye-Hepatitis B surface antigen (HBsAg), indawo "S" (Surface). Le RTS ke ibonakaliswa ngokubambisana kwiiseli zeyeast ukuze ivelise amasuntswana afana nentsholongwane abonisa zombini iprotein ye-sporozoite (indawo engu-R ephindayo ene-T) kunye no-S kumphezulu wazo. Isahlulo sesibini sika-"S" sichazwa njenge-HBsAg engadityaniswanga edibanisa ngokuzenzekelayo kwicandelo le-RTS, kungoko igama elithi RTS,S.  

Esinye isitofu sokugonya esenziwe ngokuchaseneyo malariya Ingaba i DNA-Isitofu sokugonya esisebenzisa umntu i-adenovirus ukuvakalisa iprotheni ye-sporozoite kunye ne-antigen (i-apical membrane antigen 1)⁴. Ulingo lwesigaba sesi-2 lugqityiwe kubathathi-nxaxheba abangama-82 kwiSigaba 1-2 solingo lweleyibhile evulekileyo engakhethi cala yokuvavanya uKhuseleko, ukuZinzisa, kunye nokusebenza kakuhle kwesi sitofu sokugonya kwiMpilo. Malariya-Abadala abangenalwazi e-US. Olona khuselo lokhuselo lufunyenwe ngokuchasene malariya Ukulandela ugonyo ngesitofu sokugonya esisekwe kwi-adenovirus yaba ngama-27%.  

Kwesinye isifundo, i-adenovirus yabantu yatshintshwa yaba yi-chimpanzee adenovirus kunye nenye i-antigen, i-TRAP (iprotheni enamathelayo enxulumene ne-thrombospondin) yaxutywa kwiprotheni ye-sporozoite kunye ne-apical membrane antigen ukunyusa ukhuseleko.⁵. Impendulo yesitofu kwesi sitofu sokugonya esisi-antigen esingaphantsi kweyunithi yayingama-25% xa kuthelekiswa ne--2% kwisitofu sokugonya seyunithi ephantsi emibini xa kuthelekiswa.  

Ezi zifundo zingentla zibonisa ukuba ukusetyenziswa kwe DNA i-adenovirus esekwe kwi-multi-subunit zokugonya inokubonelela ngokhuseleko olungcono (njengoko kukhankanyiwe ngasentla) kwaye njengoko kunjalo kuphononongo oluboniswe ngogonyo lwamva nje lwe-Oxford/AstraZeneca ChAdOx1 nCoV-2019 ngokuchasene ne-COVID-19 esebenzisa i-adenovirus eyenziwe ngokwemfuza njenge-vector ukuvakalisa iprotein ye-spike njenge-antigen. Le teknoloji ingasetyenziswa ukubonisa iithagethi ezininzi zeeprotheyini ukujolisa isifo seengcongconi I-parasite phambi kokuba yosulele iiseli zesibindi. Ugonyo lwangoku oluvunyiweyo lwe-WHO lisebenzisa ubuchwepheshe obahlukileyo. Noko ke, ixesha liya kuxela ukuba siya kufumana nini isitofu sokugonya isifo seengcongconi esinokunyamekela umthwalo wezifo kumazwe aseAfrika nakuMzantsi-Asia ukuze sivumele ihlabathi ukuba lisoyise esi sifo sibulalayo. 

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Ucaphulo:

1. Clyde DF, Uninzi H, McCarthy VC, Vanderberg JP. Ukugonywa kwendoda ngokuchasene ne-sporozite-induced falciparum malaria. NdinguJ Med Sci. 1973;266(3):169–77. Epub 1973/09/01. IPubMed PMID: 4583408. DOI: https://doi.org/10.1097/00000441-197309000-00002 

2. Oneko, M., Steinhardt, LC, Yego, R. okqhubekayo. Ukhuseleko, i-immunogenicity kunye nokusebenza kakuhle kwe-PfSPZ Isitofu sokugonya kwi-malaria kwiintsana ezisentshona yeKenya: uvavanyo oluphindwe kabini oluyimfama, olungenamkhethe, olulawulwa yi-placebo. Nat Med 27, 1636-1645 (2021). https://doi.org/10.1038/s41591-021-01470-y 

3. Laurens M., 2019. RTS,S/AS01 isitofu (iMosquirix™): isishwankathelo. Umntu Iigonya kunye ne-Immunotherapeutics. Umqulu 16, 2020 – Umba 3. Ipapashwe kwi-intanethi: 22 Oct 2019. DOI: https://doi.org/10.1080/21645515.2019.1669415 

4. Chuang I., Sedegah M., et al 2013. DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum I-CSP kunye ne-AMA1 yenza uKhuseleko oluNzalo oluNxulunyaniswe ne-Cell-Mediated Immunity. I-PLOS enye. Ipapashwe: ngoFebruwari 14, 2013. DOI: https://doi.org/10.1371/journal.pone.0055571 

5. Sklar M., Maiolatesi,S., et al 2021. I-antigen ezintathu IPlasmodium falciparum DNA prime-Adenovirus boost irejimeni yokugonya isifo seengcongconi iphezulu kwirejimeni ye-antigen ezimbini kwaye ikhusela ngokuchasene nokulawulwa kosulelo lwemalariya kubantu abadala abanempilo ye-malaria-naïve. I-PLOS enye. Ipapashwe: ngoSeptemba 8, 2021. DOI: https://doi.org/10.1371/journal.pone.0256980 

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