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Allurar rigakafin Nicotine

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Allurar rigakafin Nicotine
Bayanai
Ƙaramin ɓangare na medical treatment (en) Fassara
Medical condition treated (en) Fassara nicotine dependence (en) Fassara
mai lura da yanda akayiwa mutane allurar
Allurar nicotine
Zanen allurar rigakafin nicotine

Alurar rigakafin Nicotine Ta kasance wata sabuwar rigakafi ce domin magance jarabar nicotine . [1] Alurar rigakafin nicotine yana amfani da rigakafi mai aiki azaman hanyar da za ta haifar da ƙwayoyin rigakafi na polyclonal zuwa antigens, waɗanda ake amfani da su domin magance cin zarafin miyagun ƙwayoyi. [2] Sa'an nan kuma tsarin rigakafi zai iya gano nicotine a matsayin wani abu na waje kuma ya fara maganin rigakafi da ke niyya da miyagun ƙwayoyi. Sakamakon haka, adadin nicotine da ke shiga cikin kwakwalwa zai ragu bayan an yi maganin alurar riga kafi. [3] A cikin bincike na yau da kullun, allurar rigakafin nicotine sun nuna ikon magance mummunan tasirin cutar ta nicotine, amma babu ɗayan allurar rigakafin da aka haɓaka da aka ba da izini don amfani da su a cikin gwaje-gwajen asibiti azaman dabarun daina shan taba. [4] A ka'ida, rage tasirin nicotine mai lada ya kamata ya haifar da daina shan taba. Wasu kamfanoni sun gwada rigakafin ɗan takara a gwaje-gwajen asibiti, amma shaida ta kasa nuna isassun martanin rigakafin ƙwayoyin cuta ko kuma nuna ingantaccen inganci ga abubuwan da suka shafi placebo. [5]

Shaƙuwa da Janjewa

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Nicotine yana haɓaka sakin dopamine a cikin synapse

Manufar rigakafin nicotine shine don hana sake komawa shan taba. Nazarin da suka gabata sun gano cewa yankin ventral tegmental yanki (VTA) wanda ke cikin neurons dopaminergic, shine inda nicotine ke ɗaure da kunna mai karɓar nAChR ɗin sa, wanda ya haifar da sakin dopamine. [6] Baya ga saki na dopamine, akwai ƙarin ƙwayoyin cuta waɗanda aka saki, waɗanda suka haɗa da norepinephrine, acetylcholine, serotonin, γ-aminobutyric acid (GABA), glutamate, da endorphins . [7]

Taba, wanda Hukumar Lafiya ta Duniya ta yi la'akari da amfani da ita a matsayin annoba ta duniya, yana dauke da sinadarin nicotine. [8] Ƙara yawan matakan dopamine yana ƙaruwa wanda ke haifar da dogara ga miyagun ƙwayoyi, wanda masu shan taba sukan fuskanci matsaloli yayin aiwatar da janyewar nicotine. [6]

Babban neurotransmitter dopamine yana ba da gudummawa mai ƙarfi ga tsarin lada [9] wanda masu shan sigari suka samu kuma sun ruwaito, kamar tashin hankali, ingantaccen aiki, jin daɗi da ingantacciyar yanayi, waɗanda duk jihohin tunani ne da ake so.[10]

Alamun janyewar nicotine sun haɗa da damuwa, damuwa, fushi, yanayin damuwa, wahalar maida hankali, ƙara jin yunwa, ƙara yawan ci, rashin barci, da jaraba ga taba. [7] Masu shan taba da suka ci karo da waɗannan alamun janyewar mara kyau sun zaɓi su guje wa irin waɗannan abubuwan mara kyau kuma su sake shan taba don sauƙaƙe alamun janyewar nicotine, wanda ke haifar da koma baya. [7]

Tsarin tsari

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Tsarin tsarin rigakafi na nicotine ya ƙunshi ƙarin adjuvants zuwa haɗin kai tsakanin abubuwan da aka samo asali na miyagun ƙwayoyi [6] wanda ke raba kamanceceniya da nicotine, da furotin mai ɗaukar hoto na immunogenic. Gabaɗaya, an san wannan tsari da maganin alurar riga kafi.

Mai haɗawa yana da mahimmanci don haɗa hapten zuwa furotin mai ɗauka, yana samar da madaidaicin lissafi don ɗaure hapten zuwa ƙwayoyin B. Masu haɗawa kuma suna tabbatar da cewa adadin nicotine haptens da ake samu don ɗaure ga ƙwayoyin B shine mafi kyau.[11] Sunadaran da aka yi amfani da su duka suna iya samar da amsawar rigakafi.[11]

Hanyar aiki

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Nicotinic Acetylcholine mai karɓa

Nicotine, wani abu na dabi'a na jaraba da ke cikin taba, yana aiki a matsayin agonist don mai karɓar nicotinic acetylcholine (nAChR). Alurar riga kafi yana haifar da ƙoƙari na yin koyi da tsarin nicotine tun lokacin da ake samu na nicotine (rabin rayuwar nicotine = 1-2). sa'o'i) ba su da ƙarancin aiki na physiologically fiye da mahallin iyaye. [2] Alurar rigakafin nicotine immunogens ne da ke tattare da magungunan roba da ke faruwa waɗanda ke da alaƙa da masu ɗauke da ƙwayoyin cuta, waɗanda daga nan aka tattara su a cikin adjuvants don haɓaka rigakafi . [4] Alurar riga kafi yana haifar da amsawar rigakafi mai ƙarfi daga jiki ta hanyar ƙarfafa samar da ƙwayoyin rigakafi, wanda ake gudanarwa ta hanyar allurar rigakafi .

Kwayoyin magani tare da tsarin tsarinsa da aka canza kuma ana kiran mai haɗin sinadarai a matsayin hapten. Sashin rigakafi na rigakafi yana da alaƙa da abin da ke faruwa ta hanyar haɗin furotin / macromolecular. Dukkanin tsarin ana kiransa furotin-conjugated protein/macromolecular carrier. Adjuvants abubuwa ne da abun ciki na aluminium waɗanda ke ƙarfafa rigakafi ta hanyar haɓaka halayen rigakafi ga antigen. Ana yawan amfani da adjuvant na rigakafi don hana shan muggan kwayoyi. [12]

Kunna tantanin halitta na T-dogara

Ana allurar rigakafi masu haɗaka don isar da maganin, wanda ke kunna ƙwayoyin B da T a cikin hanyar da ta dogara da tantanin halitta na polyclonal anti-nicotine antibodies. Alurar riga kafi yana fallasa zuwa ga lymphocytes ta sel masu gabatar da antigen. Akwai gane peptide antigen ta masu karɓar T-cell. [13] Tare da shigar da cytokines da ƙwayoyin B, an haifar da amsa mai ban dariya [13], wanda ya haifar da kira na ƙwayoyin cuta. Kwayoyin Plasmatic suna samar da immunoglobulins, anti-nicotine antibodies wanda ke ɗaure ga nicotine. Nicotine da takamaiman ƙwayoyin rigakafin nicotine an haɗa su tare, suna yin hadaddun. Rukunin yana hana nicotine wucewa ta shingen kwakwalwar jini, saboda haka yana hana shi kaiwa nAChRs na kwakwalwa. [4]

Kayawar Kwakwalwar Jini [14] 

Bayanin wannan shine lokacin da ƙwayoyin rigakafin nicotine suka ɗaure ga ƙwayoyin nicotine ana samun karuwa a cikin girman kwayoyin halitta. Wannan yana toshe shi daga wucewa ta shingen kwakwalwar jini, don haka nicotine ba zai iya samar da nau'ikan da yawa don nuna tasirin CNS ba. Wannan yana hana haɓakar adrenaline da dopamine, [13] waɗanda ke da alaƙa da tasirin CNS masu lada waɗanda ke haifar da jaraba, ta haka ne ke hana tasirin magunguna na nicotine.

Madadin daina shan taba

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Bupropion [15]

Kawai maye gurbin nicotine (faci ko danko), bupropion antidepressant, da agonist mai karɓa na nicotinic varenicline an yarda da su don taimakawa masu amfani da taba su rage shan taba yayin gudanar da jaraba. [16] Duk da haka, kasa da kashi ɗaya bisa uku na masu karɓar magani sun daina aiki, kuma kashi ɗaya bisa uku ne kawai suka yi nasarar barin fiye da watanni shida. [17] Bugu da ƙari, fiye da rabin waɗanda suka karɓi maganin daina shan taba sun dawo. [18] Ana buƙatar sabbin dabaru don magance wannan muhimmin al'amari na kiwon lafiya a tsakiyar waɗannan cikas don haɓaka daina shan taba.

Hanyoyin tushen rigakafi, irin su amfani da alluran rigakafi don magance jaraba, an rubuta su a cikin wallafe-wallafen tun 1960s da 1970s. [19] Yawancin masu bincike sun sake kimanta rigakafin yayin da illolin da ke da alaƙa da amfani da maye gurbin nicotine lasisi suka taso. [20] Saboda iyawar su don samar da manyan ƙwayoyin rigakafin IgG anti-magungunan, allurar rigakafin haɗin gwiwa suna nuna yuwuwar a matsayin madadin hanyar magance rikice-rikicen amfani da miyagun ƙwayoyi . [2]

Jerin allurar rigakafin nicotine da aka haɓaka kuma an haɗa su cikin gwaji sun haɗa da Nic-QB (NIC002), NicVax, Niccine da TA-NIC. [9]

Kalubalen ci gaba

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Duk da ƙwaƙƙwaran ƙoƙarin da aka yi don bincikar ingancin abubuwan da ke faruwa na tushen nicotine tare da tsayi daban-daban, polarities, da sassauƙa, samun isasshen isasshen ƙarfi da kwanciyar hankali na rigakafi na tsawon lokaci babban ƙalubale ne. [21]

Duk da cewa yin amfani da allurar rigakafin nicotine na iya haifar da manyan matakan rigakafin nicotine don ɗaure dukkan ƙwayoyin nicotine da rage tasirin nicotine akan kwakwalwa ta hanyar hana rarrabawar ta, ƙimar rarrabawa akai-akai (Kd) zai ƙayyade ko akwai yuwuwar juyawa. dauri.[11]

Sashi

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Jimlar alluran farko guda uku da aka raba tsakanin makonni 2-4 ana amfani da su a cikin tsarin rigakafin haɗin gwiwa. Ayyukan rigakafi ya dogara da abubuwa biyu. Fasali na farko shine “ titer ”, wanda ke nufin adadin ƙwayoyin rigakafin da ke akwai, kuma abu na biyu shine “ƙaunar” anti-nicotine antibody zuwa nicotine.[11]

Ana kaiwa matakin titer mafi girma tsakanin makonni 2-4 bayan allura guda ɗaya sannan a fara raguwa har sai an ba da allurar ƙara don kiyaye matakan rigakafin nicotine, saboda lalacewa [2] na rigakafi. Abubuwan ƙarfafa rigakafin sun dace don amfani, yawanci watanni 2-3 bayan allurar farko ta ƙarshe. [22] [23] Ko da yake rigakafin cututtuka na iya zama da amfani na shekaru da yawa ba tare da allura masu ƙarfafawa ba, maganin rigakafi na iya buƙatar ɗan gajeren lokaci na tsawon shekara ɗaya ko ƙasa da haka. [2]

Dalilin ƙarfafawa

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Karamin girman kwayoyin nicotine yana samar da ƙananan nauyin kwayoyinsa, kuma tsarin garkuwar jikin mutum ba zai iya amsawa tare da amsawar rigakafi ba. Don haka hanya da aiki da ke bayan allurar nicotine ta hanyar gudanar da maganin alurar rigakafi akai-akai don kiyaye mahimman matakan ƙwayoyin rigakafin nicotine. Wannan dalili ya samo asali ne daga la'akari da lalatawar ƙwayar cuta ta therapeutic. [13]

Martanin rigakafi na biyu [24]

Manufar yin amfani da abin ƙarfafawa ya bambanta da tsarin rigakafin farko na rigakafin nicotine-conjugate. Alurar riga kafi na farko alama ce ta farko ta tsarin rigakafi tare da antigen, wanda shine yadda ƙwaƙwalwar ƙwayar cuta ke aiki. [25] Maganin ƙarfafawa shine don samar da ƙwayoyin rigakafi waɗanda ke amfani da ƙwaƙwalwar tsarin rigakafi game da haɗuwa da antigens. Wannan dabarar za ta ba da damar maganin rigakafi don samar da mafi sauri da ingantaccen amsa ga antigen . [13]

Tasiri mara kyau

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Nazarin asibiti tare da hodar iblis da nicotine, waɗanda aka saba amfani da allurai na 200 ko 400 micrograms a kowane kashi, sun nuna tabbataccen shaida cewa allurai na magungunan rigakafi, har zuwa 2 MG a kowace kashi, an daidaita su daidai da matakan titer . [26] [27] Tunda babu tasirin rufin, waɗannan binciken suna nuna cewa mafi kyawun kashi shine mafi girman kashi na maganin da za'a iya gudanarwa ba tare da haifar da mummuna ba. Ya zuwa yanzu, babu wani binciken maganin alurar riga kafi na asibiti da ya sami wasu manyan munanan halayen ga magungunan ƙwayoyi ko alluran rigakafin. [27]

Ribobi da rashin amfani

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Dabarar da aka fi so don magance matsalolin amfani da miyagun ƙwayoyi ita ce rigakafi mai aiki saboda yana da ingantacciyar lafiya da dacewa saboda tasirin yana dawwama ko da bayan allurai da yawa na maganin. [4] Idan aka kwatanta da ƙananan magungunan ƙwayoyin cuta, alluran rigakafi suna da tsayin lokaci na aiki saboda suna haifar da ƙwayoyin rigakafi na IgG tare da tsawon rabin rayuwa. [2]

Haɗaɗɗen rigakafin rigakafi suna aiki azaman masu adawa da rigakafi waɗanda ke hana ingancin abubuwan da ake nufi. Magungunan rigakafin ƙwayoyin cuta ba su shafar masu karɓar ƙwayoyi a cikin kwakwalwa ko kewaye, sabili da haka, illolin da ke tattare da su ba su da kyau. [2]

Wani ƙarin fa'ida na allurar haɗin gwiwa shine cewa su na duniya ne kuma ana iya ƙirƙira su don kai hari ga kowane magani ɗaya ko haɗin magunguna a ka'idar. [2]

Duk da yana da tasiri mai dorewa, martanin rigakafin rigakafin dabarun rigakafin yana da jinkirin kwatankwacinsa. [20]

Ba a kafa tasirin hanyar rigakafin aiki ba a cikin canjin hali. Ba sa rage alamun janyewa ko sha'awar ƙwayoyi. [2]

inganci

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Gwajin dabbobi

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Don samar da ƙwayoyin rigakafi don auna adadin nicotine a cikin jinin ɗan adam da fitsari, an haɗa trans-3′-succinimidylmethyl nicotine conjugate zuwa KLH kuma an ba da shi ga zomaye. [20] Ba da daɗewa ba, an ƙirƙiri wani 6- (p-aminobenzamide) na nicotine conjugate na tushen BSA-conjugated maganin rigakafi, kuma an sake nuna shi don haifar da samfurin dabba don samar da amsawar rigakafi akan nicotine. [20] An gano ƙwayoyin rigakafin da aka samar suna da babban alaƙa ga nicotine a wurare daban-daban na ɗaure, waɗanda ke da ƙarfi da ƙarfi don amfani da su. [20] Bayan karbar maganin alurar riga kafi tare da alurar riga kafi da aka yi da 6-(carboxymethylurea)-() -nicotine conjugate hade tare da KLH, berayen sun samar da kwayoyin rigakafin da ke daure nicotine sosai a cikin plasma amma ba su da tasiri akan matakan nicotine a cikin kwakwalwa, yana iyakance maganin alurar. m inganci. [20] Nazarin dabbobi ya sami nasara yayin amfani da ƙarin hanyoyin zamani. [20] Matakan nicotine a cikin kwakwalwar bera da aikin motsa jiki na bera don amsa ƙalubalen nicotine an saukar da su ta hanyar rigakafi ta hanyar amfani da haɗin gwiwar da ba nicotine ba wanda ke da alaƙa da KLH ta hanyar furotin mai haɗin gwiwa (wanda aka yiwa lakabi da NIC). [3]

A cikin primates waɗanda ba na ɗan adam ba, haɗin nicotine na ƙarni na biyu da ake kira NIC7 ya nuna yuwuwar samar da ƙwayoyin rigakafin nicotine, wanda zai iya rage ƙwayar ƙwayar cuta a cikin kwakwalwa. [21] [28] An nuna cewa allurar rigakafin nicotine gaba ɗaya (SEL-068) wanda ke ƙunshe da hapten da ba a tantance ba yana hana wariyar nicotine a cikin waɗanda ba na ɗan adam ba. [29] [30]

Gwajin asibiti na ɗan adam

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Sakamako na 'yan takarar rigakafin da dama da suka kai ga gwajin ɗan adam, gabaɗaya, sun kasance masu karaya. [20]

A cikin gwaji na Phase I wanda ya shafi masu shan taba 68, maganin 3'-AmNic-rEPA, wanda kuma aka sani da "NicVax," 3'-aminomethyl nicotine conjugate da aka haɗa zuwa Pseudomonas aeruginosa exoprotein A, ya nuna amsa mai kyau. [20] Yawancin allurai sun haifar da matakan ƙauracewa mafi girma, kuma maganin yana da ingantaccen bayanin martaba. [31] Bincike mai kyau daga gwaji na kashi na II ya nuna sakamako mai ƙarfi na antibody da kuma mafi girman yawan barin kashi a cikin rukunin jiyya idan aka kwatanta da rukunin placebo. [26] An ci gaba da rigakafin zuwa gwajin lokaci na III, amma ya kasa cimma ƙarshensa a matsayin saƙo guda ɗaya ko a hade tare da varenicline da shawara. [32]

A cikin gwaje-gwajen, maganin rigakafi na Niccine tetanus toxoid conjugate, wanda ke da ingantaccen bayanin martaba, ya nuna tasiri mai kama da haka ba tare da canza halayen masu shan taba ba. [33] NIC-002 yana ƙunshe da nicotine da aka haɗa zuwa ƙwayoyin cuta-kamar ƙwayoyin cuta, kuma ya kasa cimma manyan maƙasudin ƙarshen asibiti a cikin gwaji. [34] Ya nuna ɗan ƙaramin adadin daina shan taba a cikin watanni biyu amma babu wani canji a cikin watanni shida. [34] An janye TA-NIC tun lokacin da ta kasa kai ga ƙarshen asibiti. [20]

Duk da gwaje-gwajen asibiti da yawa, har yanzu akwai ƙarancin shaidar da ke goyan bayan alluran rigakafin a matsayin ingantaccen maganin hana shan miyagun ƙwayoyi. Karancin martanin antibody, martanin antibody na ɗan gajeren lokaci, bambance-bambancen mutum a cikin martanin antibody, da ci gaba da amfani da abubuwa a gaban amsawar rigakafin suna ba da gudummawa ga ingancin da ba a so. [12]

Manazarta

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  1. ↑ Wadgave U, Nagesh L (July 2016). "Nicotine Replacement Therapy: An Overview". International Journal of Health Sciences. 10 (3): 425–435. doi:10.12816/0048737. PMC 5003586. PMID 27610066.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Bremer PT, Janda KD (July 2017). "Conjugate Vaccine Immunotherapy for Substance Use Disorder". Pharmacological Reviews. 69 (3): 298–315. doi:10.1124/pr.117.013904. PMC 5482184. PMID 28634286. S2CID 7978508. Cite error: Invalid <ref> tag; name "Bremer_2017" defined multiple times with different content
  3. ↑ 3.0 3.1 Carrera MR, Ashley JA, Hoffman TZ, Isomura S, Wirsching P, Koob GF, Janda KD (February 2004). "Investigations using immunization to attenuate the psychoactive effects of nicotine". Bioorganic & Medicinal Chemistry. 12 (3): 563–570. doi:10.1016/j.bmc.2003.11.029. PMID 14738965. Cite error: Invalid <ref> tag; name "Carrera_2004" defined multiple times with different content
  4. ↑ 4.0 4.1 4.2 4.3 McMahon LR (March 2019). "Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics". Expert Review of Clinical Pharmacology. 12 (3): 189–195. doi:10.1080/17512433.2019.1570844. PMC 6786486. PMID 30650314. Cite error: Invalid <ref> tag; name "McMahon_2019" defined multiple times with different content
  5. ↑ Rigotti NA (January 2017). "Pharmacotherapy for smoking cessation in adults". UpToDate. Waltham (MA). Archived from the original on 2023-06-09. Retrieved 2023-06-21.
  6. ↑ 6.0 6.1 6.2 Raupach T, Hoogsteder PH, Onno van Schayck CP (March 2012). "Nicotine vaccines to assist with smoking cessation: current status of research". Drugs. 72 (4): e1-16. doi:10.2165/11599900-000000000-00000. PMC 3702960. PMID 22356293. Cite error: Invalid <ref> tag; name "Raupach_2012" defined multiple times with different content
  7. ↑ 7.0 7.1 7.2 Benowitz NL (2009). "Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics". Annual Review of Pharmacology and Toxicology. 49: 57–71. doi:10.1146/annurev.pharmtox.48.113006.094742. PMC 2946180. PMID 18834313. Cite error: Invalid <ref> tag; name "Benowitz_2009" defined multiple times with different content
  8. ↑ "Tobacco". www.who.int (in Turanci). Archived from the original on 2021-07-09. Retrieved 2023-03-13.
  9. ↑ 9.0 9.1 Scendoni R, Bury E, Ribeiro IL, Cameriere R, Cingolani M (November 2022). "Vaccines as a preventive tool for substance use disorder: A systematic review including a meta-analysis on nicotine vaccines' immunogenicity". Human Vaccines & Immunotherapeutics. 18 (6): 2140552. doi:10.1080/21645515.2022.2140552. PMC 9746524 Check |pmc= value (help). PMID 36351881 Check |pmid= value (help). Cite error: Invalid <ref> tag; name "Scendoni_2022" defined multiple times with different content
  10. ↑ Institute of Medicine (US) Committee on Preventing Nicotine Addiction in Children and Youths (1994). "The Nature of Nictine Addiction". In Lynch BS, Bonnie RJ (eds.). Growing up Tobacco Free: Preventing Nicotine Addiction in Children and Youths. Washington (DC): National Academies Press (US).
  11. ↑ 11.0 11.1 11.2 11.3 Pentel PR, LeSage MG (2014). "New directions in nicotine vaccine design and use". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. 69. pp. 553–580. doi:10.1016/B978-0-12-420118-7.00014-7. ISBN 9780124201187. PMC 4047682. PMID 24484987.
  12. ↑ 12.0 12.1 Bloom BT, Bushell MJ (May 2022). "Vaccines against Drug Abuse-Are We There Yet?". Vaccines. 10 (6): 860. doi:10.3390/vaccines10060860. PMC 9230984 Check |pmc= value (help). PMID 35746468 Check |pmid= value (help). Cite error: Invalid <ref> tag; name "Bloom_2022" defined multiple times with different content
  13. ↑ 13.0 13.1 13.2 13.3 13.4 Goniewicz ML, Delijewski M (January 2013). "Nicotine vaccines to treat tobacco dependence". Human Vaccines & Immunotherapeutics. 9 (1): 13–25. doi:10.4161/hv.22060. PMC 3667928. PMID 23108361. Cite error: Invalid <ref> tag; name "Goniewicz_2013" defined multiple times with different content
  14. ↑ "The Blood Brain Barrier and Astrocytes type 1". 1 October 2010. Archived from the original on 8 April 2023. Retrieved 12 April 2023.
  15. ↑ "Zyban Generika rezeptfrei sicher kaufen" [Buy generic Zyban safely without a prescription]. www.top-apotheke.at (in Jamusanci). Archived from the original on 2023-04-12. Retrieved 2023-04-12.
  16. ↑ Cahill K, Stevens S, Lancaster T (January 2014). "Pharmacological treatments for smoking cessation". JAMA. 311 (2): 193–194. doi:10.1001/jama.2013.283787. PMID 24399558.
  17. ↑ Rigotti NA (October 2012). "Strategies to help a smoker who is struggling to quit". JAMA. 308 (15): 1573–1580. doi:10.1001/jama.2012.13043. PMC 4562427. PMID 23073954.
  18. ↑ Collins SE, Witkiewitz K, Kirouac M, Marlatt GA (November 2010). "Preventing Relapse Following Smoking Cessation". Current Cardiovascular Risk Reports. 4 (6): 421–428. doi:10.1007/s12170-010-0124-6. PMC 4636196. PMID 26550097.
  19. ↑ Myagkova MA, Morozova VS (October 2018). "Vaccines for substance abuse treatment: new approaches in the immunotherapy of addictions". Russian Chemical Bulletin (in Turanci). 67 (10): 1781–1793. doi:10.1007/s11172-018-2290-5. ISSN 1066-5285. S2CID 105196028.
  20. ↑ 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 Hossain MK, Davidson M, Kypreos E, Feehan J, Muir JA, Nurgali K, Apostolopoulos V (October 2022). "Immunotherapies for the Treatment of Drug Addiction". Vaccines. 10 (11): 1778. doi:10.3390/vaccines10111778. PMC 9697687 Check |pmc= value (help). PMID 36366287 Check |pmid= value (help). Cite error: Invalid <ref> tag; name "Hossain_2022" defined multiple times with different content
  21. ↑ 21.0 21.1 Pryde DC, Jones LH, Gervais DP, Stead DR, Blakemore DC, Selby MD, et al. (2013). "Selection of a novel anti-nicotine vaccine: influence of antigen design on antibody function in mice". PLOS ONE. 8 (10): e76557. Bibcode:2013PLoSO...876557P. doi:10.1371/journal.pone.0076557. PMC 3788104. PMID 24098532. Cite error: Invalid <ref> tag; name "Pryde_2013" defined multiple times with different content
  22. ↑ McCluskie MJ, Thorn J, Mehelic PR, Kolhe P, Bhattacharya K, Finneman JI, et al. (April 2015). "Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates". International Immunopharmacology. 25 (2): 518–527. doi:10.1016/j.intimp.2015.02.030. PMID 25737198.
  23. ↑ Maoz A, Hicks MJ, Vallabhjosula S, Synan M, Kothari PJ, Dyke JP, et al. (October 2013). "Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter". Neuropsychopharmacology. 38 (11): 2170–2178. doi:10.1038/npp.2013.114. PMC 3773666. PMID 23660705. S2CID 6193430.
  24. ↑ "Humeral Secondary Immune Response". 24 March 2022.
  25. ↑ Sette A, Crotty S (September 2022). "Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines". Immunological Reviews. 310 (1): 27–46. doi:10.1111/imr.13089. PMC 9349657 Check |pmc= value (help). PMID 35733376 Check |pmid= value (help).
  26. ↑ 26.0 26.1 Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, et al. (March 2011). "Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic". Clinical Pharmacology and Therapeutics. 89 (3): 392–399. doi:10.1038/clpt.2010.317. PMC 4106715. PMID 21270788. Cite error: Invalid <ref> tag; name "Hatsukami_2011" defined multiple times with different content
  27. ↑ 27.0 27.1 Martell BA, Mitchell E, Poling J, Gonsai K, Kosten TR (July 2005). "Vaccine pharmacotherapy for the treatment of cocaine dependence". Biological Psychiatry. 58 (2): 158–164. doi:10.1016/j.biopsych.2005.04.032. PMID 16038686. S2CID 22415520.
  28. ↑ McCluskie MJ, Thorn J, Gervais DP, Stead DR, Zhang N, Benoit M, et al. (December 2015). "Anti-nicotine vaccines: Comparison of adjuvanted CRM197 and Qb-VLP conjugate formulations for immunogenicity and function in non-human primates". International Immunopharmacology. 29 (2): 663–671. doi:10.1016/j.intimp.2015.09.012. PMID 26404190.
  29. ↑ Fraser CC, Altreuter DH, Ilyinskii P, Pittet L, LaMothe RA, Keegan M, et al. (May 2014). "Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates". Vaccine. 32 (24): 2896–2903. doi:10.1016/j.vaccine.2014.02.024. PMID 24583006.
  30. ↑ Desai RI, Bergman J (August 2015). "Effects of the Nanoparticle-Based Vaccine, SEL-068, on Nicotine Discrimination in Squirrel Monkeys". Neuropsychopharmacology. 40 (9): 2207–2216. doi:10.1038/npp.2015.64. PMC 4613610. PMID 25742871.
  31. ↑ Hatsukami DK, Rennard S, Jorenby D, Fiore M, Koopmeiners J, de Vos A, et al. (November 2005). "Safety and immunogenicity of a nicotine conjugate vaccine in current smokers". Clinical Pharmacology and Therapeutics. 78 (5): 456–467. doi:10.1016/j.clpt.2005.08.007. PMID 16321612. S2CID 1218556.
  32. ↑ Hoogsteder PH, Kotz D, van Spiegel PI, Viechtbauer W, van Schayck OC (August 2014). "Efficacy of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial". Addiction. 109 (8): 1252–1259. doi:10.1111/add.12573. PMID 24894625.
  33. ↑ Tonstad S, Heggen E, Giljam H, Lagerbäck PÅ, Tønnesen P, Wikingsson LD, et al. (September 2013). "Niccine®, a nicotine vaccine, for relapse prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial". Nicotine & Tobacco Research. 15 (9): 1492–1501. doi:10.1093/ntr/ntt003. PMID 23471101.
  34. ↑ 34.0 34.1 Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, van Melle G, et al. (June 2008). "A vaccine against nicotine for smoking cessation: a randomized controlled trial". PLOS ONE. 3 (6): e2547. Bibcode:2008PLoSO...3.2547C. doi:10.1371/journal.pone.0002547. PMC 2432028. PMID 18575629.
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