Alurar rigakafin zazzabin cizon sauro: Shin Sabbin Fasahar Alurar rigakafin DNA Za Su Yi Tasirin Koyarwar Nan gaba?

Samar da rigakafin cutar zazzabin cizon sauro na daga cikin manyan kalubalen da ke gaban kimiyya. Mosquirix^TM , kwanan nan WHO ta amince da rigakafin cutar zazzabin cizon sauro. Ko da yake ingancin wannan allurar ya kai kusan kashi 37%, amma duk da haka wannan babban ci gaba ne domin wannan shi ne karon farko da aka ga wata allurar rigakafin zazzabin cizon sauro a ranar. Daga cikin sauran masu neman rigakafin cutar zazzabin cizon sauro, da DNA alluran rigakafin da ke amfani da adenovirus a matsayin vector na magana, tare da yuwuwar samar da antigens na zazzabin cizon sauro da yawa da alama suna da babban fa'ida kamar yadda fasahar da aka yi amfani da ita kwanan nan ta tabbatar da cancantarta a cikin yanayin Oxford/AstraZeneca (ChAdOx1 nCoV-2019) rigakafin COVID-19.  

Magunguna da da zazzabin cizon sauro sun tabbatar da cewa sun zama ƙalubale saboda sarƙaƙƙiyar tarihin rayuwa ta parasite wanda ke nuna matakai daban-daban na haɓakawa tare da mai gida, bayyanar da adadi mai yawa na sunadaran sunadaran a matakai daban-daban, tsaka-tsakin tsaka-tsakin tsaka-tsakin kwayoyin halitta da rigakafi na masauki, haɗe tare da. rashin isassun kayan aiki da kuma rashin ingantaccen hadin gwiwa a duniya saboda yaduwar cutar a galibin kasashen duniya na uku. 

Koyaya, an yi ƙoƙari kaɗan don samarwa da haɓaka ingantaccen rigakafin wannan muguwar cuta. Duk waɗannan an rarraba su azaman pre-erythrocytic alurar riga kafi yayin da suke haɗa furotin sporozoite kuma suna kai hari ga parasite kafin ya shiga cikin ƙwayoyin hanta. Na farko da ya bunkasa shine radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) maganin rigakafi¹ wanda zai ba da kariya P. falciparum kamuwa da cuta a cikin da zazzabin cizon sauro-masu butulci. GSK da Walter Reed Army Institute of Research (WRAIR) ne suka haɓaka wannan a tsakiyar 1970s amma ba su ga hasken rana ba saboda babu wani ingantaccen ingancin rigakafin da aka nuna. Gwaje-gwaje na Phase 2 na baya-bayan nan da aka gudanar a cikin jarirai 336 masu shekaru 5-12 watanni don tantance aminci, juriya, rigakafi da ingancin rigakafin PfSPZ a cikin jarirai a cikin babban watsawa. da zazzabin cizon sauro a yammacin Kenya (NCT02687373)², Har ila yau, ya nuna irin wannan sakamakon cewa ko da yake an sami karuwa mai dogara da kashi a cikin amsawar antibody a cikin watanni 6 a cikin mafi ƙasƙanci- kuma mafi girman ƙungiyoyi, amsawar T cell ba a iya ganowa a duk ƙungiyoyin kashi. Saboda rashin ingantaccen ingancin rigakafin, an yanke shawarar kada a bi wannan maganin a cikin wannan rukunin shekaru. 

Wani maganin da GSK da WRAIR suka samar a 1984 shine maganin RTS, S, wanda ake kira Mosquirix.^TM wanda ke hari akan furotin sporozoite kuma shine alurar riga kafi na farko da aka yi gwajin lokaci na 3³ da kuma na farko da za a tantance a shirye-shiryen rigakafi na yau da kullun a wuraren da zazzabin cizon sauro ke fama da shi. Sakamakon wannan gwaji ya nuna cewa a cikin yara masu shekaru 5-17 da suka sami allurai 4 na rigakafin RTS, S, ingancin maganin zazzabin cizon sauro ya kasance 36% sama da shekaru 4 na bin diddigin. RTS,S ya ƙunshi R, wanda ke nufin yankin maimaitawa na tsakiya, tandem guda ɗaya da aka adana sosai maimaita tetrapeptide NANP, T tana nufin T-lymphocyte epitopes Th2R da Th3R. Haɗaɗɗen peptide na RT an haɗa ta ta hanyar gado zuwa N-terminal na Hepatitis B surface antigen (HBsAg), yankin “S” (Surface). Ana nuna wannan RTS tare a cikin ƙwayoyin yisti don samar da ƙwayoyin cuta-kamar ƙwayoyin cuta waɗanda ke nuna furotin sporozoite (R maimaita yanki tare da T) da S a saman su. An bayyana ɓangaren “S” na biyu azaman HBsAg wanda ba a haɗa shi da shi ba wanda ya haɗa kai tsaye zuwa sashin RTS, saboda haka sunan RTS,S.  

Wani maganin rigakafi da aka samar da shi da zazzabin cizon sauro ne DNA-Ad rigakafin da ke amfani da ɗan adam adenovirus kamuwa da cuta don bayyana furotin sporozoite da antigen (apical membrane antigen 1)⁴. An kammala gwaje-gwajen lokaci na 2 akan mahalarta 82 a cikin gwaji na Buɗaɗɗen lakabi na Mataki na 1-2 don tantance Tsaro, Immunogenicity, da Tasirin wannan rigakafin a cikin Lafiya. da zazzabin cizon sauro- Manya Naive A Amurka. Mafi girman rigakafi da aka samu akansa da zazzabin cizon sauro Bayan allurar rigakafi tare da wannan maganin subunit na tushen adenovirus ya kasance kashi 27%.  

A cikin wani binciken, an canza adenovirus ɗan adam zuwa adenovirus chimpanzee da kuma wani antigen, TRAP (protein mai haɗawa da thrombospondin) an haɗa shi zuwa furotin sporozoite da antigen apical membrane antigen don haɓaka kariya.⁵. Amsar rigakafin a cikin wannan allurar rigakafin antigen guda uku shine 25% idan aka kwatanta da -2% a cikin allurar raka'a biyu idan aka kwatanta.  

Abubuwan da ke sama sun nuna cewa amfani da DNA adenovirus tushen multi-subunit alurar riga kafi na iya samun ingantacciyar kariya (kamar yadda aka ambata a sama) haka kuma kamar yadda lamarin yake a cikin binciken da aka nuna tare da kwanan nan na Oxford/AstraZeneca ChAdOx1 nCoV-2019 rigakafin COVID-19 wanda ke amfani da kwayar halittar adenovirus a matsayin vector don bayyana furotin mai karu azaman antigen. Ana iya yin amfani da wannan fasaha don bayyana maƙasudin furotin da yawa don niyya zazzabin cizon sauro parasite kafin ya cutar da kwayoyin hanta. Alurar rigakafin da WHO ta amince da ita na amfani da wata fasaha ta daban. Duk da haka, lokaci zai nuna lokacin da za mu sami ingantaccen rigakafin cutar zazzabin cizon sauro wanda zai iya kula da nauyin cututtuka na Afirka da na Kudancin Asiya don ba da damar duniya ta shawo kan wannan mummunar cuta. 

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References:

1. Clyde DF, Mafi H, McCarthy VC, Vanderberg JP. Yin rigakafi ga mutum daga cutar malaria mai haifar da 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. et al. Tsaro, rigakafi da inganci na PfSPZ Alurar rigakafin zazzabin cizon sauro a jarirai a yammacin Kenya: makafi biyu, bazuwar, gwajin lokaci na 2 mai sarrafa wuribo. Nat Med 27, 1636-1645 (2021). https://doi.org/10.1038/s41591-021-01470-y 

3. Laurens M., 2019. RTS, S/AS01 rigakafi (Mosquirix™): dubawa. Mutum Magunguna & Immunotherapeutics. Juzu'i na 16, 2020 - Fitowa ta 3. An buga akan layi: 22 Oct 2019. DOI: https://doi.org/10.1080/21645515.2019.1669415 

4. Chuang I., Sedegah M., et al 2013. DNA Prime/Adenovirus Yana Ƙarfafa Rufin Rinjayen Maganin Malaria P. falciparum CSP da AMA1 Suna haifar da Kariyar Bakar Haɗe da Kariya mai Matsakaicin Ƙwayoyin Halitta. PLOS Daya. An buga: Fabrairu 14, 2013. DOI: https://doi.org/10.1371/journal.pone.0055571 

5. Sklar M., Maiolates, S., et al 2021. A uku-antigen Plasmodium falciparum DNA Prime-Adenovirus yana haɓaka tsarin rigakafin cutar zazzabin cizon sauro ya fi na tsarin antigen guda biyu kuma yana ba da kariya daga kamuwa da cutar zazzabin cizon sauro a cikin manya marasa lafiya na malaria. PLOS Daya. An buga: Satumba 8, 2021. DOI: https://doi.org/10.1371/journal.pone.0256980 

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