ʻO nā lāʻau lapaʻau Anti-Malaria: E loaʻa hou anei ka ʻenehana DNA Vaccine hou e hoʻoikaika i ka papa e hiki mai ana?

ʻO ka hoʻomohala ʻana i ka lāʻau lapaʻau e kūʻē i ka maʻi malaria kekahi o nā pilikia nui ma mua o ka ʻepekema. Mosquirix^TM , ua ʻae ʻia ka lāʻau lapaʻau e kūʻē i ka malaria e WHO. ʻOiai ʻo ka maikaʻi o kēia kano ma kahi o 37%, akā he hana nui kēia i mua no ka mea ʻo kēia ka manawa mua i ʻike ʻia ai kekahi lāʻau lapaʻau anti-malaria. Ma waena o nā moho lāʻau lapaʻau anti-malaria ʻē aʻe, ʻo ka DNA ʻO nā lāʻau lapaʻau e hoʻohana ana i ka adenovirus ma ke ʻano he vector hōʻike, me ka hiki ke hāʻawi i nā antigens malarial he nui ka mana e like me ka ʻenehana i hoʻohana ʻia i kēia manawa i hōʻoia i kona kūpono i ka hihia o Oxford/AstraZeneca (ChAdOx1 nCoV-2019) kano kūʻē iā COVID-19.  

ʻO nā maʻi ku malaria ua hōʻike ʻia he paʻakikī ma muli o ka mōʻaukala ola paʻakikī o ka parasite e hōʻike ana i nā pae hoʻomohala like ʻole me ka mea hoʻokipa, ka hōʻike ʻana o ka nui o nā protein like ʻole i nā pae like ʻole, kahi pilina paʻakikī ma waena o ka biology parasite a me ka palekana host, hui pū me ka nele i nā kumuwaiwai kūpono a me ka nele o ka launa pū ʻana o ka honua ma muli o ka laha ʻana o ka maʻi ma ka hapa nui o nā ʻāina ʻekolu. 

Eia nō naʻe, ua hana ʻia kekahi mau hoʻāʻo e hana a hoʻomohala i kahi kano kūpono e kūʻē i kēia maʻi weliweli. Ua helu ʻia kēia mau mea āpau ma ke ʻano he pre-erythrocytic nā lāʻau āpau no ka mea, pili lākou i ka protein sporozoite a hoʻopaʻa i ka parasite ma mua o ke komo ʻana i loko o nā pūnaʻi ate. ʻO ka mea mua i hoʻomohala ʻia he radiation-attenuated ʻO Plasmodium falciparum sporozoite (PfSPZ) kano¹ e hoomalu aku ai P. falciparum maʻi i loko malaria- nā mākua naʻaupō. Ua hoʻomohala ʻia kēia e GSK a me ka Walter Reed Army Institute of Research (WRAIR) i ka waena o 1970s akā ʻaʻole i ʻike i ka mālamalama o ka lā no ka mea ʻaʻohe mea nui i hōʻike ʻia. ʻO nā hoʻokolohua Phase 2 hou i mālama ʻia i nā pēpē 336 makahiki 5-12 mahina e hoʻoholo ai i ka palekana, ka ʻae ʻana, ka immunogenicity a me ka pono o ka Vaccine PfSPZ i nā pēpē i kahi hoʻouna kiʻekiʻe. malaria e kau ana ma ke komohana o Kenya (NCT02687373)², ua hōʻike pū i nā hopena like ʻoiai ʻoiai aia ka piʻi ʻana o ka nui o nā pane antibody ma 6 mau mahina ma nā pūʻulu haʻahaʻa a kiʻekiʻe loa, ʻaʻole hiki ke ʻike ʻia nā pane T cell ma nā hui āpau āpau. Ma muli o ka loaʻa ʻole o ka pono o ka lāʻau lapaʻau koʻikoʻi, ua hoʻoholo ʻia ʻaʻole e alualu i kēia kano i kēia pūʻulu makahiki. 

ʻO kekahi lāʻau lapaʻau ʻē aʻe i hoʻomohala ʻia e GSK a me WRAIR i ka makahiki 1984 ʻo ia ka lāʻau lapaʻau RTS,S, i kapa ʻia ʻo Mosquirix^TM ʻo ia ka mea i hoʻopaʻa ʻia i ka protein sporozoite a ʻo ia ke kano mua i loaʻa i kahi hoʻokolohua Phase 3.³ a ʻo ka mea mua i loiloi ʻia i nā papahana kaʻi maʻamau ma nā wahi e hoʻopau ʻia ai ka malaria. Hōʻike nā hopena o kēia hoʻāʻo ʻana ma waena o nā keiki 5-17 mau mahina i loaʻa i 4 mau kau o ka lāʻau lapaʻau RTS,S, ʻo ka maikaʻi o ka maʻi malaria he 36% ma mua o 4 mau makahiki o ka hahai ʻana. Aia i loko o ka RTS,S ka R, e pili ana i kahi ʻāpana hoʻihoʻi waena, hoʻokahi tandem i mālama nui ʻia i ka tetrapeptide NANP, ʻo T e pili ana i ka T-lymphocyte epitopes Th2R a me Th3R. Hoʻohui ʻia ka peptide RT i hui pū ʻia i ka N-terminal o ka Hepatitis B surface antigen (HBsAg), ka ʻāpana "S" (Surface). Hoʻopuka pū ʻia kēia RTS i loko o nā pūnaewele hū e hāʻawi i nā ʻāpana like-virus e hōʻike ana i ka protein sporozoite ʻelua (R repeat region me T) a me S ma ko lākou ʻili. Hōʻike ʻia kahi ʻāpana "S" ʻelua ma ke ʻano he HBsAg i hoʻohui ʻole ʻia e hoʻopili koke i ka mea RTS, no laila ka inoa ʻo RTS,S.  

ʻO kekahi lāʻau lapaʻau i kūkulu ʻia e kūʻē malaria no ka DNA-Ad vaccine e hoʻohana ana i ke kanaka nā adenovirus e hōʻike i ka protein sporozoite a me kahi antigen (apical membrane antigen 1)⁴. Ua hoʻopau ʻia nā hoʻāʻo ʻana o ka pae 2 ma luna o 82 mau mea komo i kahi hoʻāʻo hōʻailona wehe wehe ʻole i ka Phase 1-2 e loiloi i ka palekana, Immunogenicity, a me ka Pono o kēia kano ma Healthy Malaria- ʻO nā poʻe makua naʻaupō i ka US. ʻO ka palekana sterile kiʻekiʻe loa i loaʻa malaria ma hope o ka hoʻopaʻa ʻana me kēia adenovirus-based subunit vaccine he 27%.  

Ma kekahi noiʻi ʻē aʻe, ua hoʻololi ʻia ka adenovirus kanaka i chimpanzee adenovirus a me kekahi antigen, TRAP (thrombospondin-related adhesive protein) i hui pū ʻia me ka protein sporozoite a me ka antigen membrane apical e hoʻoikaika i ka pale.⁵. ʻO ka pane ʻana o ka lāʻau lapaʻau i loko o kēia lāʻau lapaʻau ʻekolu antigen sub-unit he 25% e hoʻohālikelike ʻia me -2% i loko o nā ʻāpana ʻelua ʻāpana ʻelua ke hoʻohālikelike ʻia.  

Hōʻike nā haʻawina i luna e hoʻohana i ka DNA adenovirus ma muli o nā ʻāpana he nui nā lāʻau āpau ʻoi aku ka maikaʻi o ka palekana (e like me ka mea i ʻōlelo ʻia ma luna) a e like me ka hihia i hōʻike ʻia me ka maʻi maʻi hou o Oxford/AstraZeneca ChAdOx1 nCoV-2019 e kūʻē i ka COVID-19 e hoʻohana ana i ka genetically engineered adenovirus ma ke ʻano he vector e hōʻike i ka protein spike e like me antigen. Hiki ke hoʻohana ʻia kēia ʻenehana no ka hōʻike ʻana i nā pahuhopu protein he nui e hoʻopaʻa i ka malaria parasite ma mua o kona hoʻopili ʻana i nā pūnaeho ate. Hoʻohana ka lāʻau lapaʻau WHO i kēia manawa i kahi ʻenehana ʻokoʻa. Eia naʻe, e haʻi mai ka manawa i ka wā e loaʻa ai iā mākou kahi maʻi malarial maikaʻi e hiki ke mālama i ke kaumaha o ka maʻi o ʻApelika a me nā ʻāina Hema-Asia e ʻae i ka honua e lanakila i kēia maʻi make. 

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E hoʻomaopopo ':

1. Clyde DF, Most H, McCarthy VC, Vanderberg JP. ʻO ka pale ʻana o ke kanaka i ka maʻi malaria falciparum i hoʻokomo ʻia i ka sporozite. 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. ¶ AL. Ka palekana, immunogenicity a me ka pono o ka PfSPZ Vaccine e kū'ē i ka maʻi maʻi ma ke komohana o Kenya: kahi hoʻāʻo ʻelua makapō, randomized, placebo-controlled phase 2. Nat Med 27, 1636-1645 (2021). https://doi.org/10.1038/s41591-021-01470-y 

3. Laurens M., 2019. RTS,S/AS01 vaccine (Mosquirix™): he hiʻohiʻona. Kanaka ʻO nā maʻi & Immunotherapeutics. Volume 16, 2020 – Puka 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 Hoʻokomo ʻo CSP a me AMA1 i ka pale ʻana i ka Sterile i hui pū ʻia me ka Cell-Mediated Immunity. PLOS ʻEkahi. Published: February 14, 2013. DOI: https://doi.org/10.1371/journal.pone.0055571 

5. Sklar M., Maiolatesi, S., et al 2021. He ʻekolu-antigen ʻO Plasmodium falciparum DNA prime—Ua ʻoi aku ka maikaʻi o ka hoʻomaʻamaʻa ʻana i ka maʻi maʻi maʻi maʻi maʻi ma mua o ke ʻano he ʻelua-antigen regimen a pale aku i ka maʻi maʻi malaria kanaka i hoʻopaʻa ʻia i ka maʻi malaria-naïve olakino. PLOS ʻEkahi. Published: September 8, 2021. DOI: https://doi.org/10.1371/journal.pone.0256980 

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