Tshuaj tiv thaiv kab mob malaria: Puas yuav pom tshiab DNA Tshuaj Tiv Thaiv Kev Tshawb Fawb Technology cuam tshuam rau yav tom ntej?

Kev tsim cov tshuaj tiv thaiv kab mob malaria yog qhov nyuaj tshaj plaws ua ntej kev tshawb fawb. Mosquirix^TM , ib qho tshuaj tiv thaiv kab mob malaria tsis ntev los no tau pom zoo los ntawm WHO. Txawm hais tias qhov ua tau zoo ntawm cov tshuaj tiv thaiv no yog kwv yees li 37%, tab sis qhov no yog ib kauj ruam zoo rau tom ntej vim qhov no yog thawj zaug uas cov tshuaj tiv thaiv kab mob malaria tau pom hnub no. Ntawm lwm cov tshuaj tiv thaiv kab mob malaria, cov DNA Cov tshuaj tiv thaiv siv adenovirus ua ib qho kev qhia vector, muaj peev xwm muab tau rau ntau hom kab mob malarial antigens zoo li muaj peev xwm zoo li cov cuab yeej siv tau tsis ntev los no tau ua pov thawj tias nws tsim nyog nyob rau hauv rooj plaub ntawm Oxford / AstraZeneca (ChAdOx1 nCoV-2019) tshuaj tiv thaiv tiv thaiv COVID-19.  

Cov tshuaj tiv thaiv tiv thaiv malaria tau ua pov thawj tias muaj kev sib tw vim yog lub neej nyuaj ntawm cov kab mob parasite uas nthuav tawm ntau theem kev loj hlob nrog rau hauv tus tswv tsev, qhia txog ntau cov proteins sib txawv nyob rau theem sib txawv, kev sib cuam tshuam ntawm cov kab mob kab mob thiab cov kab mob tiv thaiv kab mob, ua ke nrog cov kab mob sib kis. tsis muaj peev txheej txaus thiab tsis muaj kev sib koom tes thoob ntiaj teb zoo vim muaj tus kab mob kis thoob plaws hauv feem ntau lub ntiaj teb thib peb. 

Txawm li cas los xij, ob peb qhov kev sim tau ua los tsim thiab tsim cov tshuaj tiv thaiv zoo tiv thaiv kab mob txaus ntshai no. Tag nrho cov no tau raug cais raws li pre-erythrocytic tshuaj tiv thaiv raws li lawv koom nrog cov protein sporozoite thiab tsom cov kab mob ua ntej nws nkag mus rau daim siab hlwb. Thawj qhov kev txhim kho yog hluav taws xob-attenuated Plasmodium falciparum tshuaj tiv thaiv sporozoite (PfSPZ).¹ uas yuav muab kev tiv thaiv tiv thaiv P. falciparum kab mob hauv malaria- neeg laus. Qhov no tau tsim los ntawm GSK thiab Walter Reed Army Institute of Research (WRAIR) nyob rau nruab nrab xyoo 1970s tab sis tsis pom lub teeb ntawm lub hnub vim tsis muaj cov tshuaj tiv thaiv tseem ceeb tau pom. Kev sim Phaj 2 tsis ntev los no uas tau ua nyob rau hauv 336 tus menyuam mos hnub nyoog 5-12 lub hlis los txiav txim siab txog kev nyab xeeb, kev zam, kev tiv thaiv kab mob thiab kev ua tau zoo ntawm PfSPZ Vaccine hauv cov menyuam mos hauv kev sib kis siab. malaria qhov chaw nyob rau sab hnub poob Kenya (NCT02687373)², kuj tau pom cov txiaj ntsig zoo sib xws tias txawm hais tias muaj qhov nce ntxiv ntawm cov tshuaj tiv thaiv kab mob hauv 6 lub hlis hauv pawg qis tshaj- thiab siab tshaj plaws, cov lus teb T cell tsis tuaj yeem kuaj pom thoob plaws txhua pawg koob tshuaj. Vim tsis muaj cov tshuaj tiv thaiv tseem ceeb, nws tau txiav txim siab tsis mus nrhiav tshuaj tiv thaiv hauv pawg hnub nyoog no. 

Lwm cov tshuaj tiv thaiv tsim los ntawm GSK thiab WRAIR xyoo 1984 yog RTS, S tshuaj tiv thaiv, hu ua Mosquirix^TM uas yog lub hom phiaj ntawm sporozoite protein thiab yog thawj cov tshuaj tiv thaiv uas tau dhau los ntawm Phase 3 sim³ thiab thawj tus uas raug soj ntsuam hauv cov kev pab cuam txhaj tshuaj txhua hnub hauv cov cheeb tsam malaria. Cov txiaj ntsig ntawm qhov kev sim no qhia tau hais tias ntawm cov menyuam yaus hnub nyoog 5-17 lub hlis uas tau txais 4 koob tshuaj RTS, S tshuaj tiv thaiv, qhov ua tau zoo ntawm malaria yog 36% dhau 4 xyoos ntawm kev soj ntsuam. RTS, S muaj R, uas yog hais txog lub hauv paus rov qab cheeb tsam, ib tug heev-conserved tandem rov tetrapeptide NANP, T yog hais txog T-lymphocyte epitopes Th2R thiab Th3R. Qhov sib xyaw ua ke RT peptide yog genetic fused rau N-terminal ntawm kab mob siab B nto antigen (HBsAg), thaj tsam "S" (Surface). Qhov RTS no yog sib koom ua ke hauv cov kab mob poov xab kom tawm tau cov kab mob zoo li cov kab mob uas nthuav tawm ob qho tib si sporozoite protein (R rov ua dua thaj tsam nrog T) thiab S ntawm lawv qhov chaw. Ib qho thib ob "S" yog qhia raws li ib qho tsis siv HBsAg uas spontaneously fuses rau RTS tivthaiv, li no lub npe RTS, S.  

Lwm cov tshuaj tiv thaiv uas tau tsim tawm tsam malaria yog lub DNA-Cov tshuaj tiv thaiv uas siv tib neeg kab mob adenovirus los nthuav qhia cov protein sporozoite thiab ib qho antigen (apical membrane antigen 1)⁴. Kev sim theem 2 tau ua tiav ntawm 82 tus neeg koom hauv Phase 1-2 uas tsis yog-randomized qhib daim ntawv sim los ntsuas kev nyab xeeb, kev tiv thaiv kab mob, thiab kev ua tau zoo ntawm cov tshuaj tiv thaiv no hauv Kev Noj Qab Haus Huv malaria-Neev cov neeg laus nyob hauv Teb Chaws Asmeskas. Qhov kev tiv thaiv tsis zoo tshaj plaws tau ua tiav tawm tsam malaria Tom qab txhaj tshuaj tiv thaiv kab mob adenovirus-based subunit vaccine yog 27%.  

Hauv lwm txoj kev tshawb fawb, tib neeg adenovirus tau hloov mus rau chimpanzee adenovirus thiab lwm yam antigen, TRAP (thrombospondin-related adhesive protein) tau fused rau sporozoite protein thiab apical membrane antigen los txhim kho kev tiv thaiv.⁵. Cov tshuaj tiv thaiv kab mob hauv peb qhov tshuaj tiv thaiv kab mob no yog 25% piv rau -2% hauv ob qhov tshuaj tiv thaiv sub-unit thaum piv.  

Cov kev tshawb fawb saum toj no qhia tias kev siv ntawm DNA adenovirus raws li multi-subunit tshuaj tiv thaiv tej zaum yuav them taus kev tiv thaiv zoo dua (raws li tau hais los saum toj no) thiab kuj zoo ib yam li cov ntaub ntawv hauv kev tshawb fawb pom nrog Oxford / AstraZeneca ChAdOx1 nCoV-2019 cov tshuaj tiv thaiv tsis ntev los no tiv thaiv COVID-19 uas siv genetic engineered adenovirus ua tus vector los nthuav qhia cov protein ntau li antigen. Cov thev naus laus zis no tuaj yeem siv los nthuav qhia ntau lub hom phiaj muaj protein ntau rau lub hom phiaj malarial parasite ua ntej nws kis mus rau lub siab hlwb. Cov tshuaj tiv thaiv WHO tau pom zoo tam sim no siv cov cuab yeej sib txawv. Txawm li cas los xij, lub sijhawm yuav qhia thaum twg peb yuav tau txais cov tshuaj tiv thaiv kab mob malarial zoo uas tuaj yeem saib xyuas tus kab mob lub nra ntawm African thiab South-Asian lub teb chaws kom tso cai rau lub ntiaj teb kov yeej tus kab mob no. 

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References:

1. Clyde DF, Feem ntau H, McCarthy VC, Vanderberg JP. Kev txhaj tshuaj ntawm tus txiv neej tawm tsam sporozite-induced falciparum malaria. Am J Med Sci. 1973; 266(3): 169–77. Epub 1973/09/01. PubMed PMID: 4583408. DOI: https://doi.org/10.1097/00000441-197309000-00002 

2. Oneko, M., Steinhardt, LC, Yego, R. et al. Kev nyab xeeb, kev tiv thaiv kab mob thiab kev ua tau zoo ntawm PfSPZ Tshuaj Tiv Thaiv malaria hauv cov menyuam mos nyob rau sab hnub poob Kenya: ob qhov muag tsis pom kev, randomized, placebo-tswj theem 2 mus sib hais. Nat Med 27, 1636-1645 (2021). https://doi.org/10.1038/s41591-021-01470-y 

3. Laurens M., 2019. RTS, S/AS01 vaccine (Mosquirix™): ib qho kev piav qhia. Tib neeg Cov tshuaj tiv thaiv & Immunotherapeutics. Volume 16, 2020 – Issue 3. Published online: 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 CSP thiab AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity. PLOS Ib. Luam tawm: Lub Ob Hlis 14, 2013. DOI: https://doi.org/10.1371/journal.pone.0055571 

5. Sklar M., Maiolatesi, S., et al 2021. A peb-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen yog superior rau ob-antigen regimen thiab tiv thaiv tiv thaiv tib neeg tus kab mob malaria nyob rau hauv noj qab haus huv malaria-naïve cov neeg laus. PLOS Ib. Published: September 8, 2021. DOI: https://doi.org/10.1371/journal.pone.0256980 

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