Allurar rigakafin zazzabin cizon sauro

Allurar rigakafin zazzabin cizon sauro
hypothetical technology (en) da vaccine type (en)
Bayanai
Ƙaramin ɓangare na	protozoan vaccines (en)
Vaccine for (en)	Zazzaɓin cizon Sauro

 

Alurar rigakafin zazzabin cizon sauro Ta kasance wata allurar rigakafin cutar zazzabin cizon sauro ne wanda sauro ke kamuwa da shi wanda ya shafi mutane miliyan 249 a duniya a cikin kasashe da yankuna 85 da ke fama da zazzabin cizon sauro kuma ya yi sanadin mutuwar 608,000 a cikin 2022.^[1] Alurar riga kafi na farko da aka amince da shi don cutar zazzabin cizon sauro shine RTS,S, wanda aka sani da sunan mai suna Mosquirix. ^[2] As of Afrilu 2023^[update] , an ba da maganin zuwa 1.5 yara miliyan da ke zaune a wuraren da zazzabin cizon sauro ya kai matsakaici zuwa sama. ^[3] Yana buƙatar aƙalla allurai uku a cikin jarirai ta hanyar shekaru 2, kuma kashi na huɗu yana ƙara kariya har tsawon shekaru 1-2. ^{[4] [5]} Alurar riga kafi yana rage yawan shiga asibiti daga cutar zazzabin cizon sauro da kusan kashi 30%. ^[4]

Ana ci gaba da bincike tare da sauran allurar rigakafin zazzabin cizon sauro. Maganin cutar zazzabin cizon sauro mafi inganci shine R21/Matrix-M, tare da ƙimar ingancin 77% da aka nuna a gwaji na farko kuma mafi girman matakan rigakafi fiye da maganin RTS,S. Ita ce rigakafin farko da ta cimma burin Hukumar Lafiya ta Duniya (WHO) na rigakafin cutar zazzabin cizon sauro tare da aƙalla kashi 75% na inganci, ^{[6] [7]} kuma kawai maganin zazzabin cizon sauro na biyu wanda WHO ta ba da shawarar. ^[8] A watan Afrilun 2023, Hukumar Abinci da Magunguna ta Ghana ta amince da yin amfani da maganin R21 don amfani da shi ga yara masu shekaru tsakanin watanni biyar zuwa shekaru uku. ^[9] Bayan shawarar Ghana, Najeriya ta amince da rigakafin R21 na wucin gadi. ^[10]

RTS, S/AS01 (sunan mai suna Mosquirix) ^[2] shine maganin zazzabin cizon sauro na farko da aka amince don amfanin jama'a. Yana buƙatar aƙalla allurai uku a cikin jarirai ta hanyar shekaru 2, tare da kashi na huɗu yana ƙara kariya har tsawon shekaru 1-2. ^[4] Alurar riga kafi yana rage yawan shiga asibiti daga cutar zazzabin cizon sauro da kusan kashi 30%. ^[4]

RTS,S an haɓaka ta PATH Malaria Vaccine Initiative (MVI) da GlaxoSmithKline (GSK) tare da tallafi daga Gidauniyar Bill da Melinda Gates . Alurar rigakafi ce mai sake haɗuwa, wanda ya ƙunshi furotin na Plasmodium falciparum circumsporozoite (CSP) daga matakin pre-erythrocytic. CSP antigen yana haifar da samar da ƙwayoyin rigakafi masu iya hana mamayewar hepatocytes kuma yana haifar da amsawar salula wanda ke ba da damar lalata hanta masu kamuwa da cuta. Alurar rigakafi ta CSP ta gabatar da matsaloli a matakin gwaji saboda rashin isasshen rigakafi . RTS,S yayi ƙoƙari ya guje wa waɗannan ta hanyar haɗa furotin tare da antigen na saman daga cutar hanta B, haifar da ƙarin ƙarfi da rigakafin rigakafi. Lokacin da aka gwada shi a cikin gwaji a matsayin emulsion na man fetur a cikin ruwa kuma tare da ƙarin adjuvants na monophosphoryl A da QS21 (SBAS2), maganin ya ba da kariya ga 7 daga cikin 8 masu aikin sa kai lokacin da aka kalubalanci P. falciparum. ^[11]

RTS,S an ƙera shi ta hanyar amfani da kwayoyin halitta daga furotin na waje na P. falciparum malaria parasite da wani yanki na kwayar cutar hanta B tare da wani sinadari don haɓaka amsawar rigakafi. Ana hana kamuwa da cuta ta hanyar haifar da manyan titers na antibody waɗanda ke toshe ƙwayar cuta daga kamuwa da hanta. ^[12] A cikin Nuwamba 2012, gwaji na Phase III na RTS,S ya gano cewa yana ba da kariya mai sauƙi daga duka na asibiti da kuma zazzabin cizon sauro a cikin ƙananan jarirai. ^[13]

A cikin Oktoba 2013, sakamakon farko na gwaji na asibiti na kashi III ya nuna cewa RTS,S/AS01 ya rage yawan lokuta a tsakanin yara ƙanana da kusan kashi 50 cikin ɗari kuma tsakanin jarirai da kusan kashi 25 cikin ɗari. Nazarin ya ƙare a cikin 2014. Tasirin kashi mai kara kuzari yana da inganci, duk da cewa tasirin gabaɗaya yana raguwa da lokaci. Bayan shekaru hudu, raguwa ya kasance kashi 36 cikin dari ga yaran da suka sami allura uku da kuma adadin kuzari. Rashin kashi mai ƙarawa yana rage tasirin cutar zazzabin cizon sauro zuwa wani sakamako mara kyau. An nuna cewa allurar ba ta da tasiri ga jarirai. Allurai uku na alluran rigakafi tare da haɓakawa sun rage haɗarin cututtukan asibiti da kashi 26 cikin ɗari sama da shekaru uku amma ba su ba da wata muhimmiyar kariya daga cutar zazzabin cizon sauro ba. ^[14]

A cikin ƙoƙari don saukar da ƙungiyar da ta fi girma kuma ta ba da tabbacin ci gaba da kasancewa ga jama'a, GSK ya nemi lasisin tallace-tallace tare da Hukumar Kula da Magunguna ta Turai (EMA) a cikin Yuli 2014.^[15] GSK ta dauki aikin a matsayin wani shiri na sa-kai, tare da mafi yawan kudaden da aka samu daga gidauniyar Gates, wadda ke taimakawa wajen kawar da zazzabin cizon sauro.^[16]

A cikin Yuli 2015, Mosquirix ya sami kyakkyawar ra'ayi na kimiyya daga Hukumar Kula da Magunguna ta Turai (EMA) game da shawarar da za a yi amfani da maganin alurar riga kafi ga yara masu shekaru 6 makonni zuwa watanni 17 a waje da Tarayyar Turai.^{[17] [2]} An kaddamar da aikin gwajin rigakafin ne a ranar 23 ga Afrilu 2019 a Malawi, a ranar 30 ga Afrilu 2019 a Ghana, da kuma ranar 13 ga Satumba 2019 a Kenya .^[18][19]

A watan Oktoba na 2021, Hukumar Lafiya ta Duniya ta amince da maganin don "amfani da yawa" ga yara, wanda ya zama rigakafin cutar zazzabin cizon sauro na farko da ya karɓi wannan shawarar.^[20][21][22]

Kungiyar WHO ce ta cancanta a cikin watan Yulin shekara ta 2022. ^[3] A watan Agustan 2022, UNICEF ta ba da kwangila ga GSK don samar da allurai guda miliyan 18 na rigakafin RTS, S sama da shekaru uku. Fiye da kasashe 30 suna da wuraren da ke da cutar zazzabin cizon sauro inda ake sa ran maganin zai yi samu amfani. ^[23]

Ya zuwa watan Afrilu na shekara ta , yara miliyan 1.5 a Ghana, Kenya da Malawi sun karɓi akalla allurar rigakafin guda ɗaya, tare da fiye da allurar rigakawa miliyan 4.5 da aka ba da su ta hanyar shirye-shiryen rigakafin yau da kullun.^[3] Kasashe 9 na gaba da za su karɓi allurar rigakafin a cikin shekaru 2 masu zuwa sune Benin, Burkina Faso, Burundi, Kamaru, Jamhuriyar Demokradiyyar Kongo, Laberiya, Nijar, Saliyo, da Uganda.^[24] 

Mafi inganci maganin zazzabin cizon sauro shine R21/Matrix-M, tare da ingancin kashi 77 da aka nuna a gwaji na farko. Ita ce rigakafin farko da ta cimma burin Hukumar Lafiya ta Duniya na maganin zazzabin cizon sauro tare da aƙalla kashi 75 cikin ɗari. ^[6] An haɓaka ta ta hanyar haɗin gwiwar da ke tattare da Cibiyar Jenner a Jami'ar Oxford, Cibiyar Nazarin Kiwon Lafiya ta Kenya, Makarantar Kiwon Lafiya ta London da Magungunan Wuta, Novavax, da Cibiyar Serum ta Indiya . An gudanar da gwaje-gwajen ne a Institut de Recherche en Sciences de la Santé da ke Nanoro, Burkina Faso tare da Halidou Tinto a matsayin babban mai bincike. ^[7] Alurar riga kafi na R21 yana amfani da sunadaran sunadaran sunadaran (CSP), a mafi girma fiye da na RTS, S. Yana amfani da tsarin haɗin HBsAg iri ɗaya, amma ba ya ƙunshi ƙarin HBsAg. ^[25] Ya haɗa da matrix-M adjuvant wanda kuma ake amfani dashi a cikin rigakafin Novavax COVID-19 . ^[26]

An ba da rahoton gwajin lokaci na II a cikin Afrilu 2021, tare da ingancin allurar rigakafi na 77% da matakan rigakafi da yawa fiye da na RTS, S. Harbin ƙarfafawa na R21/Matrix-M wanda aka ba da watanni 12 bayan tsarin kashi uku na farko yana da tasiri mai yawa akan zazzabin cizon sauro, yana ba da kariya mai girma daga cutar cizon sauro na alamar aƙalla shekaru 2. ^[27] An bayar da rahoton wani gwaji na kashi na uku tare da yara 4,800 a fadin kasashen Afirka hudu a watan Nuwamban 2022, wanda ke nuna ingancin alluran rigakafin kashi 74% a kan wani mummunan cutar zazzabin cizon sauro. ^[28] Ana tattara ƙarin bayanai daga karatu da yawa. ^[29] As of Afrilu 2023^[update] Ba a buga bayanai daga binciken kashi na III ba bisa ka'ida, amma bayanan da suka gabata daga binciken an raba su da hukumomin gudanarwa. ^[9]

Hukumar Kula da Abinci da Magunguna ta Ghana ta amince da amfani da allurar R21 a watan Afrilun 2023, don amfani da shi ga yara 'yan tsakanin watanni biyar zuwa shekaru uku. Cibiyar Serum ta Indiya tana shirin samar da allurai tsakanin allurai miliyan 100-200 a kowace shekara, kuma tana gina masana'antar rigakafin a Accra, Ghana . ^{[9] [30]} Bayan shawarar Ghana, Najeriya ta amince da rigakafin R21 na wucin gadi. ^[10]

A cikin Oktoba 2023 WHO ta amince da rigakafin R21 na zazzabin cizon sauro, karshen Disamba 2023 an saka shi cikin jerin allurar rigakafin da aka rigaya . ^[31]

Babu wata allurar rigakafi mai inganci don cutar zazzabin cizon sauro, kodayake ana ci gaba da samar da alluran rigakafi da yawa. ^[32] Masu neman alluran rigakafi da yawa waɗanda ke yin niyya zuwa matakin-jini na rayuwar parasite ɗin ba su wadatar da kansu ba. ^[33] Ana samar da wasu yuwuwar alluran rigakafi da ke niyya da matakin pre-erythrocytic, tare da RTS,S da R-21/Matrix-M zaɓuɓɓukan da aka amince da su zuwa yanzu. ^{[34] [13] [30]}

In 2015, researchers used a repetitive antigen display technology to engineer a nanoparticle that displayed malaria specific B cell and T cell epitopes. The particle exhibited icosahedral symmetry and carried on its surface up to 60 copies of the RTS,S protein. The researchers claimed that the density of the protein was much higher than the 14% of the GSK vaccine.^[35][36]

Alurar riga kafi na PfSPZ wani ɗan takara maganin zazzabin cizon sauro ne wanda Sanaria ya haɓaka ta amfani da sporozoites masu raɗaɗi da radiation don haifar da amsawar rigakafi. Gwaje-gwajen asibiti sun kasance masu ban sha'awa, tare da gwaji a Afirka, Turai, da Amurka suna kare sama da kashi 80% na masu aikin sa kai. ^[37] An fuskanci wasu suka game da yuwuwar yiwuwar samar da kayayyaki da yawa a Afirka, tunda dole ne a adana shi cikin ruwa nitrogen .

Hukumar Abinci da Magunguna ta Amurka ta ba da ɗan takarar rigakafin PfSPZ da sauri a cikin Satumba 2016. ^[38]

A cikin Afrilu 2019, an ba da sanarwar gwajin lokaci na III a Bioko, wanda aka shirya farawa a farkon 2020. ^[39]

• SPf66 allurar rigakafin peptide ce ta roba wanda ƙungiyar Manuel Elkin Patarroyo ta haɓaka a Colombia, kuma an gwada shi sosai a wuraren da ke fama da cutar a cikin 1990s. Gwaje-gwaje na asibiti sun nuna rashin isasshen inganci, tare da inganci 28% a Kudancin Amurka kuma ƙarancin inganci ko babu inganci a Afirka. ^[40] Wannan maganin ba shi da wani tasiri na kariya a cikin mafi girman gwajin da aka sarrafa bazuwar placebo a Kudancin Gabashin Asiya kuma an yi watsi da shi. ^[41]
• CSP (Circum-Sporozoite Protein) wani maganin rigakafi ne da aka samar wanda da farko ya bayyana yana da alƙawarin isa ga gwaji. Hakanan yana dogara ne akan furotin na circumsporozoite, amma kuma yana da recombinant (Asn-Ala-Pro15Asn-Val-Asp-Pro) 2-Leu-Arg ( R32LR ) sunadaran da aka haɗa tare da ingantaccen sinadarin Pseudomonas aeruginosa (A9). Duk da haka, a farkon matakin, an nuna cikakken rashin kariya ga waɗanda aka yi wa allurar. Ƙungiyar binciken da aka yi amfani da ita a Kenya tana da kashi 82% na cutar parasitaemia yayin da ƙungiyar kulawa kawai ke da kashi 89% kawai. Maganin da aka yi niyya don haifar da ƙarar amsawar T-lymphocyte a cikin waɗanda aka fallasa; wannan kuma ba a kiyaye ba.^{[ana buƙatar hujja]}
• Rikicin NYVAC-Pf7 da yawa ya yi ƙoƙarin yin amfani da fasaha daban-daban, wanda ya haɗa da ƙwayoyin antigenic P. falciparum guda bakwai. Waɗannan sun fito ne daga matakai daban-daban yayin zagayowar rayuwa. CSP da sporozoite surface protein 2 (wanda ake kira PfSSP2 ) an samo su daga lokacin sporozoite. Hanta matakin antigen 1 (LSA1), uku daga matakin erythrocytic (protein surface merozoite 1, serine repeat antigen, da AMA-1), da kuma antigen mataki guda daya (25-kDa Pfs25) an haɗa su. An fara bincikar wannan ta hanyar amfani da birai na rhesus kuma an samar da sakamako masu ƙarfafawa: 4 daga cikin 7 antigens sun samar da takamaiman martanin rigakafi (CSP, PfSSP2, MSP1 da PFs25). Gwaji daga baya a cikin mutane, duk da nuna martanin rigakafi na salula a cikin sama da kashi 90% na batutuwan, suna da mummunan martanin rigakafin mutum. Duk da wannan biyo bayan gudanar da maganin, wasu 'yan takarar sun sami cikakkiyar kariya lokacin da aka kalubalanci P. falciparum . Wannan sakamakon yana da garantin gwaji mai gudana.^{[ana buƙatar hujja]}
• A cikin 1995 gwajin filin da ya shafi [NANP] 19-5.1 ya tabbatar da nasara sosai. Daga cikin yara 194 da aka yi wa alurar riga kafi, babu wanda ya kamu da cutar zazzabin cizon sauro a cikin makonni 12 da suka biyo baya, kuma 8 ne kawai suka kasa samun mafi girman matakan rigakafin cutar. Alurar riga kafi ya ƙunshi furotin fitarwa na schizont (5.1) da maimaita 19 na furotin saman sporozoite [NANP]. Iyaka na fasaha ya wanzu saboda yana ƙunshe da 20% peptide kawai kuma yana da ƙananan matakan rigakafi. Hakanan baya ƙunsar kowane epitopes T-cell immunodominant . ^[42]
• Ginin sinadarai da ke fuskantar gwaji don maganin tarin fuka da ciwon daji-mai hana JmJc ML324 da dan takarar asibiti na antitubercular SQ109-watakila sabon layin magunguna ne don magance zazzabin cizon sauro da kuma kashe kwayar cutar a matakinsa na kamuwa da cuta. Ana buƙatar ƙarin gwaje-gwaje har yanzu kafin a amince da mahadi a matsayin ingantaccen magani.^[43]

Ayyukan haɓaka rigakafin rigakafin cutar zazzabin cizon sauro wani tsari ne mai rikitarwa. Akwai la'akari da yawa da za a yi game da dabarun da yuwuwar rigakafin ya kamata a ɗauka.

P. falciparum ya nuna iyawa, ta hanyar haɓaka ƙwayoyin cuta masu jure wa ƙwayoyi, don canjin juyin halitta. Nau'in <i id="mwAQs">Plasmodium</i> yana da babban adadin maimaitawa, fiye da yadda ake buƙata a zahiri don tabbatar da watsawa a cikin yanayin rayuwa.^{[ana buƙatar hujja]}Wannan yana ba da damar jiyya na magunguna waɗanda ke da tasiri wajen rage yawan haifuwa, amma ba dakatar da ^{<span title="This claim needs references to reliable sources. (April 2023)">shi</span> ] [} don yin babban zaɓi na zaɓi, don haka yana fifita ci gaban juriya. Tsarin canjin juyin halitta yana ɗaya daga cikin mahimman abubuwan da ake la'akari yayin la'akari da yuwuwar masu neman rigakafin. Haɓaka juriya na iya haifar da raguwar fa'ida ga kowane yuwuwar rigakafin don haka yin mara amfani da ingantaccen ingantaccen magani mai inganci. ^[44]

Kwayoyin cuta suna haifar da manyan nau'ikan amsa guda biyu daga tsarin garkuwar jikin mutum. Waɗannan su ne rigakafin cutar parasitic da rigakafi mai guba.

• "Anti-parasitic rigakafi" yana magance tushen; ya ƙunshi amsawar antibody ( rigakafi mai ban dariya ) da amsawar rigakafi ta hanyar tantanin halitta. Da kyau, maganin alurar riga kafi zai ba da damar haɓaka ƙwayoyin rigakafi na anti-plasmodial ban da samar da amsa mai matsakaicin matsakaicin tantanin halitta. Za'a tattauna yuwuwar antigens waɗanda za'a iya yin niyya akan maganin rigakafi a cikin zurfin zurfi daga baya. Kwayoyin rigakafi wani ɓangare ne na takamaiman amsawar rigakafi. Suna aiwatar da tasirin su ta hanyar kunna cascade ɗin da suka dace, suna motsa ƙwayoyin phagocytic zuwa cikin endocytosis ta hanyar mannewa saman saman abubuwan antigenic na waje, don haka 'alama' shi a matsayin m. Kariyar barkwanci ko tantanin halitta ta ƙunshi hanyoyin haɗin kai da yawa waɗanda ke da nufin hana kamuwa da cuta shiga cikin jiki (ta hanyar shinge na waje ko maƙiyi na cikin gida) sannan kuma kashe duk wani ƙananan ƙwayoyin cuta ko ƙwayoyin waje waɗanda suka sami nasarar shiga. Ƙungiyar tantanin halitta ta ƙunshi yawancin fararen jini (irin su monocytes, neutrophils, macrophages, lymphocytes, basophils, mast cells, kwayoyin kisa na halitta, da eosinophils ) waɗanda ke kaiwa ga jikin waje ta hanyoyi daban-daban. Game da cutar zazzabin cizon sauro, za a yi niyya duka tsarin biyu don ƙoƙarin ƙara yuwuwar martanin da aka samar, don haka tabbatar da mafi girman damar hana cututtuka.^{[ana buƙatar hujja]}
• "Anti-mai guba rigakafi" yana magance alamun; yana nufin ƙaddamar da amsawar rigakafi da ke hade da samar da abubuwan da ko dai haifar da bayyanar cututtuka ko kuma rage tasirin da duk wani abu mai guba (na ƙananan ƙwayoyin cuta) yana da tasiri akan ci gaban cututtuka. Alal misali, an nuna cewa ƙwayar cuta necrosis factor-alpha yana da muhimmiyar rawa wajen haifar da alamun da aka samu a cikin mummunar cutar maleriya ta P. falciparum . Don haka maganin warkewa zai iya kaiwa ga samar da TNF-a, hana damuwa na numfashi da alamun kwakwalwa. Wannan hanya tana da ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun abubuwa kamar yadda ba zai rage nauyin parasitic ba; maimakon haka, kawai yana rage cututtukan cututtukan da ke haɗuwa. Sakamakon haka, akwai matsaloli masu yawa wajen kimanta inganci a cikin gwajin ɗan adam.

Yin la'akari da wannan bayanin, ingantaccen ɗan takarar rigakafin rigakafi zai yi ƙoƙarin samar da mafi mahimmancin amsawar tantanin halitta da kuma rigakafin ƙwayoyin cuta akan gabatarwar parasite. Wannan zai sami fa'ida ta haɓaka ƙimar kawar da ƙwayoyin cuta, don haka rage gogaggun alamun bayyanar cututtuka da kuma samar da daidaitaccen rigakafi na gaba a gaba.

Maƙasudin rigakafin rigakafin cutar zazzabin cizon sauro (Dolan da Hoffman)

Matakin parasite	manufa
Sporozoite	Hepatocytes mamayewa; kai tsaye anti-sporozite
Hepatozoite	Kai tsaye anti-hepatozoite.
Asexual erythrocytic	Anti-host erythrocyte, antibodies toshe mamayewa; anti receptor ligand, anti-soluble guba
Gametocyte	Anti-gametocyte. Anti-host erythrocyte, ƙwayoyin rigakafi suna toshe hadi, ƙwayoyin rigakafi suna toshe fitowa daga sauro midgut.

Ta hanyar dabi'ar su, protozoa sun fi kwayoyin halitta da kwayoyin cuta da ƙwayoyin cuta, masu rikitarwa da tsarin rayuwa. Wannan yana gabatar da matsaloli a cikin ci gaban rigakafin amma kuma yana ƙara yawan abubuwan da za a iya kaiwa ga rigakafin. An taƙaita waɗannan a cikin matakin rayuwa da ƙwayoyin rigakafi waɗanda zasu iya haifar da amsawar rigakafi.^{[ana buƙatar hujja]}</link>^{[ <span title="This claim needs references to reliable sources. (April 2023)">abubuwan da ake bukata</span> ]}

Kwayar cutar zazzabin cizon sauro ta bambanta sosai a duk faɗin duniya kuma ta haifar da imani cewa yana iya zama dole a ɗauki dabarun haɓaka rigakafi daban-daban don kaiwa ga al'ummomi daban-daban. Ana ba da shawarar allurar rigakafin nau'in 1 ga waɗanda galibi suna fama da cutar zazzabin P. falciparum a yankin Saharar Afirka, tare da manufar farko don rage yawan masu kamuwa da cutar zazzabin cizon sauro mai tsanani da kuma mace-mace a jarirai da yaran da suka kamu da cutar. Ana iya ɗaukar rigakafin nau'in 2 a matsayin rigakafin 'matafiya',' da nufin hana duk alamun asibiti a cikin mutanen da ba su da wani fallasa a baya. Wannan wata babbar matsala ce ta lafiyar jama'a, tare da bayyanar cutar zazzabin cizon sauro a matsayin daya daga cikin manyan barazana ga lafiyar matafiya. Matsaloli tare da samuwan hanyoyin kwantar da hankali sun haɗa da farashi, samuwa, sakamako mara kyau da rashin daidaituwa, rashin jin daɗi, da yarda, da yawa daga cikinsu za a rage ko kawar da su idan an samar da maganin rigakafi mai tasiri (fiye da 85-90%).^{[ana buƙatar hujja]}</link>^{[ <span title="This claim needs references to reliable sources. (November 2013)">abubuwan da ake bukata</span> ]}

Halin rayuwa na kwayar cutar malaria yana da rikitarwa musamman, yana gabatar da matsalolin haɓaka na farko. Duk da ɗimbin yawan alluran rigakafin da ake da su, babu waɗanda ke da alaƙa da cututtukan parasitic. Matakan haɓaka daban-daban waɗanda ke cikin zagayowar rayuwa suna ba da dama da yawa don yin niyya ga antigens, don haka yana iya haifar da amsawar rigakafi. A bisa ka'ida, kowane mataki na ci gaba na iya samun maganin alurar riga kafi da aka samar da shi musamman don kai hari. Haka kuma, duk wani allurar rigakafin da aka samar zai kasance yana da ikon zama mai darajar warkewa tare da hana ci gaba da yaduwa kuma yana yiwuwa ya ƙunshi haɗin antigens daga matakai daban-daban na ci gaban parasites. Fiye da 30 daga cikin waɗannan antigens ana bincike </link> ta ƙungiyoyi a duk faɗin duniya a cikin bege na gano haɗin gwiwa wanda zai iya haifar da rigakafi a cikin mutumin da aka yi wa allurar. Wasu daga cikin hanyoyin sun haɗa da bayyanar da antigen, abubuwan hanawa na takamaiman ƙwayoyin rigakafi akan tsarin rayuwa da kuma tasirin kariya ta hanyar rigakafi ko canja wurin ƙwayoyin rigakafi tsakanin garkuwar jiki da mara lafiya. Galibin bincike kan allurar rigakafin zazzabin cizon sauro sun mayar da hankali ne kan nau’in Plasmodium falciparum saboda yawan mace-macen da kwayar cutar ke haifarwa da kuma saukin gudanar da binciken in vitro/in vivo. Maganin farko sun yi ƙoƙarin yin amfani da furotin circumsporozoite (CSP). Wannan shine mafi rinjayen antigen na farkon lokacin pre-erythrocytic. Duk da haka, an fuskanci matsalolin saboda ƙananan inganci, reactogenicity da ƙananan immunogenicity .^{[ana buƙatar hujja]}

• The initial stage in the lifecycle, following inoculation, is a relatively short "pre-erythrocytic" or "hepatic" phase. A vaccine at this stage must have the ability to protect against sporozoites invading and possibly inhibiting the development of parasites in the hepatocytes (through inducing cytotoxic T-lymphocytes that can destroy the infected liver cells). However, if any sporozoites evaded the immune system they would then have the potential to be symptomatic and cause the clinical disease.
• The second phase of the lifecycle is the "erythrocytic" or blood phase. A vaccine here could prevent merozoite multiplication or the invasion of red blood cells. This approach is complicated by the lack of MHC molecule expression on the surface of erythrocytes. Instead, malarial antigens are expressed, and it is this towards which the antibodies could potentially be directed. Another approach would be to attempt to block the process of erythrocyte adherence to blood vessel walls. It is thought that this process is accountable for much of the clinical syndrome associated with malarial infection; therefore, a vaccine given during this stage would be therapeutic and hence administered during clinical episodes to prevent further deterioration.
• The last phase of the lifecycle that has the potential to be targeted by a vaccine is the "sexual stage". This would not give any protective benefits to the individual inoculated but would prevent further transmission of the parasite by preventing the gametocytes from producing multiple sporozoites in the gut wall of the mosquito. It therefore would be used as part of a policy directed at eliminating the parasite from areas of low prevalence or to prevent the development and spread of vaccine-resistant parasites. This type of transmission-blocking vaccine is potentially very important. The evolution of resistance in the malaria parasite occurs very quickly, potentially making any vaccine redundant within a few generations. This approach to the prevention of spread is therefore essential.
• Another approach is to target the protein kinases, which are present during the entire lifecycle of the malaria parasite. Research is underway on this, yet production of an actual vaccine targeting these protein kinases may still take a long time.^[45]
• Report of a vaccine candidate capable of neutralizing all tested strains of Plasmodium falciparum, the most deadly form of the parasite causing malaria, was published in Nature Communications by a team of scientists from the University of Oxford in 2011.^[46] The viral vector vaccine, targeting a full-length P. falciparum reticulocyte-binding protein homologue 5 (PfRH5) was found to induce an antibody response in an animal model. The results of this new vaccine confirmed the utility of a key discovery reported from scientists at the Wellcome Trust Sanger Institute, published in Nature.^[47] The earlier publication reported P. falciparum relies on a red blood cell surface receptor, known as 'basigin', to invade the cells by binding a protein PfRH5 to the receptor.^[47] Unlike other antigens of the malaria parasite which are often genetically diverse, the PfRH5 antigen appears to have little genetic diversity. It was found to induce very low antibody response in people naturally exposed to the parasite.^[46] The high susceptibility of PfRH5 to the cross-strain neutralizing vaccine-induced antibody demonstrated a significant promise for preventing malaria in the long and often difficult road of vaccine development. According to Professor Adrian Hill, a Wellcome Trust Senior Investigator at the University of Oxford, the next step would be the safety tests of this vaccine. At the time (2011) it was projected that if these proved successful, the clinical trials in patients could begin within two to three years.^[48]
• PfEMP1, one of the proteins known as variant surface antigens (VSAs) produced by Plasmodium falciparum, was found to be a key target of the immune system's response against the parasite. Studies of blood samples from 296 mostly Kenyan children by researchers of Burnet Institute and their cooperators showed that antibodies against PfEMP1 provide protective immunity, while antibodies developed against other surface antigens do not. Their results demonstrated that PfEMP1 could be a target to develop an effective vaccine which will reduce risk of developing malaria.^[49][50]
• Plasmodium vivax is the common malaria species found in India, Southeast Asia and South America. It is able to stay dormant in the liver and reemerge years later to elicit new infections. Two key proteins involved in the invasion of the red blood cells (RBC) by P. vivax are potential targets for drug or vaccine development. When the Duffy binding protein (DBP) of P. vivax binds the Duffy antigen (DARC) on the surface of RBC, process for the parasite to enter the RBC is initiated. Structures of the core region of DARC and the receptor binding pocket of DBP have been mapped by scientists at the Washington University in St. Louis. The researchers found that the binding is a two-step process that involves two copies of the parasite protein acting together like a pair of tongs that "clamp" two copies of DARC. Antibodies that interfere with the binding by either targeting the key region of the DARC or the DBP will prevent the infection.^[51][52]
• Antibodies against the Schizont Egress Antigen-1 (PfSEA-1) were found to disable the parasite's ability to rupture from the infected red blood cells (RBCs), thus preventing it from continuing with its lifecycle. Researchers from Rhode Island Hospital identified Plasmodium falciparum PfSEA-1, a 244 kd malaria antigen expressed in the schizont-infected RBCs. Mice vaccinated with the recombinant PfSEA-1 produced antibodies which interrupted the schizont rupture from the RBCs and decreased the parasite replication. The vaccine protected the mice from the lethal challenge of the parasite. Tanzanian and Kenyan children who have antibodies to PfSEA-1 were found to have fewer parasites in their bloodstream and a milder case of malaria. By blocking the schizont outlet, the PfSEA-1 vaccine may work synergistically with vaccines targeting the other stages of the malaria lifecycle such as hepatocyte and RBC invasion.^[53][54]

Ana iya samun haɓaka yuwuwar rigakafin da aka haifar akan Plasmodia ta yunƙurin ƙaddamar da matakai da yawa a cikin rayuwa. Wannan kuma yana da fa'ida wajen rage yuwuwar haɓakar ƙwayoyin cuta masu juriya. Yin amfani da antigens da yawa-parasites na iya samun sakamako na aiki tare ko ƙari.

Ɗaya daga cikin masu neman maganin alurar riga kafi a gwaji na asibiti ya ƙunshi sunadaran antigenic da suka sake haɗawa zuwa furotin na circumsporozoite . ^[55]

Mutanen da suka kamu da kwayar cutar a cikin ƙasashe masu fama da cutar suna samun rigakafi daga cututtuka da mutuwa. Irin wannan rigakafi baya hana kamuwa da cutar maleriya; Mutanen da ke da rigakafi sukan ɗauki kwayoyin cutar asymptomatic a cikin jininsu. Wannan yana nuna, duk da haka, yana nuna cewa yana yiwuwa a ƙirƙiri martanin rigakafi wanda ke ba da kariya daga cutarwar ƙwayar cuta.

Bincike ya nuna cewa idan aka dauki immunoglobulin daga manya masu rigakafi, an tsarkake su, sannan a ba wa mutanen da ba su da wani kariya, za a iya samun wasu kariya. ^[56]

A cikin 1967, an ba da rahoton cewa za a iya ba da matakin rigakafi ga ƙwayar ƙwayar cuta ta Plasmodium berghei ga beraye ta hanyar fallasa su ga sporozoites waɗanda aka lalata su ta hanyar x-ray. ^[57] Nazarin ɗan adam na baya a cikin 1970s ya nuna cewa za a iya yiwa ɗan adam rigakafi daga Plasmodium vivax da Plasmodium falciparum ta hanyar fallasa su ga cizon adadi mai yawa na sauro da ba su da iska. ^[58]

Daga 1989 zuwa 1999, masu sa kai goma sha ɗaya da aka ɗauka daga Ma'aikatar Kiwon Lafiyar Jama'a ta Amurka, Sojojin Amurka, da Sojojin Ruwa na Amurka an yi musu rigakafi daga Plasmodium falciparum ta cizon sauro na 1001-2927 waɗanda aka lalata da rads 15,000 na gamma radiation daga Co. -60 ko Cs-137 tushen. ^[59] Wannan matakin radiation ya isa ya rage ƙwayar cutar zazzabin cizon sauro ta yadda, yayin da suke iya shiga cikin ƙwayoyin hanta, ba za su iya haɓaka zuwa schizonts ba kuma ba za su iya cutar da jajayen ƙwayoyin jini ba. ^[59] A cikin tsawon makonni 42, gwaje-gwaje 24 cikin 26 da aka yi wa masu aikin sa kai sun nuna cewa an kare su daga cutar zazzabin cizon sauro. ^[59]

 

• "Malaria Vaccines". PubChem. U.S. National Library of Medicine.
• Malaria Vaccine Initiative
• Malaria vaccines UK
• Gates Foundation Global Health: Malaria

1. ↑ World Malaria Report 2023 - World Health Organization. Switzerland: World Health Organization. 30 November 2023. ISBN 978-92-4-006489-8.
2. ↑ ^{2.0 2.1 2.2} "Mosquirix: Opinion on medicine for use outside EU". European Medicines Agency (EMA). Archived from the original on 23 November 2019. Retrieved 22 November 2019. Cite error: Invalid <ref> tag; name "EMA Mosquirix" defined multiple times with different content
3. ↑ ^{3.0 3.1 3.2} "Q&A on RTS,S malaria vaccine - WHO". World Health Organization (in Turanci). 19 April 2023. Retrieved 29 April 2023. Cite error: Invalid <ref> tag; name "who-rts" defined multiple times with different content
4. ↑ ^{4.0 4.1 4.2 4.3} "First malaria vaccine hits 1 million dose milestone — although it has its shortcomings". NPR. 13 May 2022. Archived from the original on 13 November 2022. Retrieved 2 January 2023. Cite error: Invalid <ref> tag; name "npr-052022" defined multiple times with different content
5. ↑ World Health Organization (2022). "Malaria vaccine: WHO position paper – March 2022". Weekly Epidemiological Record. 97 (9): 60–78. |hdl-access= requires |hdl= (help)
6. ↑ ^{6.0 6.1} "Malaria vaccine hailed as potential breakthrough". BBC News. 23 April 2021. Archived from the original on 24 April 2021. Retrieved 24 April 2021. Cite error: Invalid <ref> tag; name "bbc-r21" defined multiple times with different content
7. ↑ ^{7.0 7.1} "Malaria vaccine becomes first to achieve WHO-specified 75% efficacy goal". EurekAlert!. 23 April 2021. Archived from the original on 27 July 2021. Retrieved 24 April 2021. Cite error: Invalid <ref> tag; name "EurekAlert042021" defined multiple times with different content
8. ↑ "WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization" (in Turanci). 2 October 2023. Retrieved 4 October 2023.
9. ↑ ^{9.0 9.1 9.2} "Ghana first to approve 'world-changer' malaria vaccine". BBC News (in Turanci). 12 April 2023. Archived from the original on 13 April 2023. Retrieved 13 April 2023. Cite error: Invalid <ref> tag; name "bbc-r21-202304" defined multiple times with different content
10. ↑ ^{10.0 10.1} "The country with the highest rate of malaria deaths in the world has approved Oxford's vaccine". Quartz (in Turanci). 18 April 2023. Retrieved 19 April 2023. Cite error: Invalid <ref> tag; name "qz-202304" defined multiple times with different content
11. ↑ "RTS,S malaria candidate vaccine reduces malaria by approximately one-third in African infants". malariavaccine.org. Malaria Vaccine Initiative Path. Archived from the original on 23 March 2013. Retrieved 19 March 2013.
12. ↑ Foquet L, Hermsen CC, van Gemert GJ, Van Braeckel E, Weening KE, Sauerwein R, et al. (January 2014). "Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection". The Journal of Clinical Investigation. 124 (1): 140–4. doi:10.1172/JCI70349. PMC 3871238. PMID 24292709.
13. ↑ ^{13.0 13.1} Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, et al. (December 2012). "A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants". The New England Journal of Medicine. 367 (24): 2284–95. doi:10.1056/NEJMoa1208394. PMC 10915853 Check |pmc= value (help). PMID 23136909. Cite error: Invalid <ref> tag; name "doi10.1056/NEJMoa1208394" defined multiple times with different content
14. ↑ "Malaria vaccine candidate shown to prevent thousands of cases". www.gizmag.com. 27 April 2015. Archived from the original on 6 May 2016. Retrieved 11 June 2016.
15. ↑ "GSK announces EU regulatory submission of malaria vaccine candidate RTS,S" (Press release). GSK. 24 July 2014. Archived from the original on 4 December 2016. Retrieved 30 July 2015.
16. ↑ Kelland K (7 October 2013). "GSK aims to market world's first malaria vaccine". Reuters. Archived from the original on 18 January 2016. Retrieved 9 December 2013.
17. ↑ "First malaria vaccine receives positive scientific opinion from EMA" (Press release). European Medicines Agency (EMA). 24 July 2015. Archived from the original on 3 October 2018. Retrieved 30 July 2015.
18. ↑ Alonso P (19 June 2019). "Letter to partners – June 2019" (Press release). Wuxi: World Health Organization. Archived from the original on 31 January 2022. Retrieved 22 October 2019.
19. ↑ "Malaria vaccine launched in Kenya: Kenya joins Ghana and Malawi to roll out landmark vaccine in pilot introduction" (Press release). Homa Bay: World Health Organization. 13 September 2019. Archived from the original on 22 October 2019. Retrieved 22 October 2019.
20. ↑ Davies L (6 October 2021). "WHO endorses use of world's first malaria vaccine in Africa". The Guardian. Archived from the original on 7 October 2021. Retrieved 6 October 2021.
21. ↑ "WHO recommends groundbreaking malaria vaccine for children at risk" (Press release). World Health Organization. Archived from the original on 7 October 2021. Retrieved 6 October 2021.
22. ↑ Mandavilli A (6 October 2021). "A 'Historical Event': First Malaria Vaccine Approved by W.H.O." The New York Times. Archived from the original on 7 October 2021. Retrieved 6 October 2021.
23. ↑ "Millions more children to benefit from malaria vaccine as UNICEF secures supply". UNICEF (in Turanci). 16 August 2022. Archived from the original on 2 January 2023. Retrieved 2 January 2023.
24. ↑ Devi S (July 2023). "12 countries to get first doses of malaria vaccine". Lancet. 402 (10397): 172. doi:10.1016/s0140-6736(23)01456-3. PMID 37454658 Check |pmid= value (help). S2CID 259849056 Check |s2cid= value (help).
25. ↑ Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, et al. (May 2021). "Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial". The Lancet. 397 (10287): 1809–1818. doi:10.1016/S0140-6736(21)00943-0. PMC 8121760 Check |pmc= value (help). PMID 33964223 Check |pmid= value (help).
26. ↑ "Great Malaria Vaccine News". Science Translational Medicine. 23 April 2021. Archived from the original on 15 April 2023. Retrieved 24 April 2021.
27. ↑ Datoo MS, Natama HM, Somé A, Bellamy D, Traoré O, Rouamba T, et al. (December 2022). "Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial". The Lancet. Infectious Diseases (in English). 22 (12): 1728–1736. doi:10.1016/S1473-3099(22)00442-X. PMID 36087586 Check |pmid= value (help). S2CID 252149462 Check |s2cid= value (help).CS1 maint: unrecognized language (link)
28. ↑ "Malaria Vaccine Candidate 'Impressive' in Phase III Test". MedPage Today (in Turanci). 3 November 2022. Archived from the original on 22 January 2023. Retrieved 22 January 2023.
29. ↑ "New data buoy hopes for promising malaria vaccine—but questions remain". Science Magazine (in Turanci). 3 November 2022. Archived from the original on 4 November 2022. Retrieved 22 January 2022.
30. ↑ ^{30.0 30.1} "Ghana first to approve Oxford's malaria vaccine". Reuters (in Turanci). 12 April 2023. Archived from the original on 13 April 2023. Retrieved 13 April 2023. Cite error: Invalid <ref> tag; name "reuters-r21-202304" defined multiple times with different content
31. ↑ "WHO prequalifies a second malaria vaccine, a significant milestone in prevention of the disease". www.who.int (in Turanci). Retrieved 2024-01-11.
32. ↑ Abuga KM, Jones-Warner W, Hafalla JC (February 2021). "Immune responses to malaria pre-erythrocytic stages: Implications for vaccine development". Parasite Immunology. 43 (2): e12795. doi:10.1111/pim.12795. PMC 7612353. PMID 32981095.
33. ↑ Graves P, Gelband H (October 2006). "Vaccines for preventing malaria (blood-stage)". The Cochrane Database of Systematic Reviews. 2006 (4): CD006199. doi:10.1002/14651858.CD006199. PMC 6532641. PMID 17054281.
34. ↑ Graves P, Gelband H (October 2006). "Vaccines for preventing malaria (pre-erythrocytic)". The Cochrane Database of Systematic Reviews. 2006 (4): CD006198. doi:10.1002/14651858.CD006198. PMC 6532586. PMID 17054280.
35. ↑ "Researcher's nanoparticle key to new malaria vaccine". Research & Development. 4 September 2014. Archived from the original on 11 August 2016. Retrieved 20 October 2023.
36. ↑ Burkhard P, Lanar DE (2 December 2015). "Malaria vaccine based on self-assembling protein nanoparticles". Expert Review of Vaccines. 14 (12): 1525–7. doi:10.1586/14760584.2015.1096781. PMC 5019124. PMID 26468608.
37. ↑ "Nature report describes complete protection after 10 weeks with three doses of PfSPZ- CVac" (Press release). 15 February 2017. Archived from the original on 23 April 2021. Retrieved 26 August 2020.
38. ↑ "SANARIA PfSPZ VACCINE AGAINST MALARIA RECEIVES FDA FAST TRACK DESIGNATION" (PDF). Sanaria Inc. 22 September 2016. Archived from the original (PDF) on 23 October 2016. Retrieved 23 January 2017.
39. ↑ Butler D (April 2019). "Promising malaria vaccine to be tested in first large field trial". Nature. doi:10.1038/d41586-019-01232-4. PMID 32291409. S2CID 145852768.
40. ↑ Graves P, Gelband H (April 2006). "Vaccines for preventing malaria (SPf66)". The Cochrane Database of Systematic Reviews. 2006 (2): CD005966. doi:10.1002/14651858.CD005966. PMC 6532709. PMID 16625647.
41. ↑ Nosten F, Luxemburger C, Kyle DE, Ballou WR, Wittes J, Wah E, et al. (September 1996). "Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group". Lancet. 348 (9029): 701–707. doi:10.1016/s0140-6736(96)04465-0. PMID 8806288. S2CID 54282604.
42. ↑ Ratanji KD, Derrick JP, Dearman RJ, Kimber I (April 2014). "Immunogenicity of therapeutic proteins: influence of aggregation". Journal of Immunotoxicology. 11 (2): 99–109. doi:10.3109/1547691X.2013.821564. PMC 4002659. PMID 23919460.
43. ↑ Heiberg T (15 January 2021). "South African scientists discover new chemicals that kill malaria parasite". Reuters (in Turanci). Archived from the original on 1 February 2021. Retrieved 2 February 2021.
44. ↑ Kennedy DA, Read AF (December 2018). "Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance". Proceedings of the National Academy of Sciences of the United States of America. 115 (51): 12878–12886. Bibcode:2018PNAS..11512878K. doi:10.1073/pnas.1717159115. PMC 6304978. PMID 30559199.
45. ↑ Zhang VM, Chavchich M, Waters NC (March 2012). "Targeting protein kinases in the malaria parasite: update of an antimalarial drug target". Current Topics in Medicinal Chemistry. 12 (5): 456–72. doi:10.2174/156802612799362922. PMID 22242850. Archived from the original on 30 May 2013. Retrieved 23 March 2020.
46. ↑ ^{46.0 46.1} Douglas AD, Williams AR, Illingworth JJ, Kamuyu G, Biswas S, Goodman AL, et al. (December 2011). "The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody". Nature Communications. 2 (12): 601. Bibcode:2011NatCo...2..601D. doi:10.1038/ncomms1615. PMC 3504505. PMID 22186897.
47. ↑ ^{47.0 47.1} Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, et al. (November 2011). "Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum". Nature. 480 (7378): 534–7. Bibcode:2011Natur.480..534C. doi:10.1038/nature10606. PMC 3245779. PMID 22080952.
48. ↑ "New candidate vaccine neutralizes all tested strains of malaria parasite". fiercebiotech.com. FierceBiotech. 21 December 2011. Archived from the original on 20 April 2012. Retrieved 23 December 2011.
49. ↑ "Lifting malaria's deadly veil: Mystery solved in quest for vaccine". Burnet Institute. 2 August 2012. Archived from the original on 18 August 2012. Retrieved 14 August 2012.
50. ↑ Chan JA, Howell KB, Reiling L, Ataide R, Mackintosh CL, Fowkes FJ, et al. (September 2012). "Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity". The Journal of Clinical Investigation. 122 (9): 3227–38. doi:10.1172/JCI62182. PMC 3428085. PMID 22850879.
51. ↑ "Scientists capture key protein structures that could aid malaria vaccine design". fiercebiotechresearch.com. 13 January 2014. Archived from the original on 18 January 2014. Retrieved 16 January 2014.
52. ↑ Batchelor JD, Malpede BM, Omattage NS, DeKoster GT, Henzler-Wildman KA, Tolia NH (January 2014). "Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC". PLOS Pathogens. 10 (1): e1003869. doi:10.1371/journal.ppat.1003869. PMC 3887093. PMID 24415938.
53. ↑ "Antigen Discovery could advance malaria vaccine". fiercebiotechresearch.com. 27 May 2014. Archived from the original on 4 March 2016. Retrieved 22 June 2014.
54. ↑ Raj DK, Nixon CP, Nixon CE, Dvorin JD, DiPetrillo CG, Pond-Tor S, et al. (May 2014). "Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection". Science. 344 (6186): 871–7. Bibcode:2014Sci...344..871R. doi:10.1126/science.1254417. PMC 4184151. PMID 24855263.
55. ↑ Plassmeyer ML, Reiter K, Shimp RL, Kotova S, Smith PD, Hurt DE, et al. (September 2009). "Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate". The Journal of Biological Chemistry. 284 (39): 26951–63. doi:10.1074/jbc.M109.013706. PMC 2785382. PMID 19633296.
56. ↑ "Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies". Immune Deficiency Foundation. Archived from the original on 15 March 2020. Retrieved 30 September 2019.
57. ↑ Nussenzweig RS, Vanderberg J, Most H, Orton C (October 1967). "Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei". Nature. 216 (5111): 160–2. Bibcode:1967Natur.216..160N. doi:10.1038/216160a0. PMID 6057225. S2CID 4283134.
58. ↑ Clyde DF (May 1975). "Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites". The American Journal of Tropical Medicine and Hygiene. 24 (3): 397–401. doi:10.4269/ajtmh.1975.24.397. PMID 808142.
59. ↑ ^{59.0 59.1 59.2} Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, et al. (April 2002). "Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites". The Journal of Infectious Diseases. 185 (8): 1155–64. doi:10.1086/339409. PMID 11930326.