探索流感病毒疫苗研發(fā)新趨勢(shì)及整體解決方案

探索流感疫苗開(kāi)發(fā)趨勢(shì)及整體解決方案

楊濱博士高級(jí)產(chǎn)品經(jīng)理北京義翹神州科技股份有限公司義翹神州CONTENT流感疫苗開(kāi)發(fā)遇到的挑戰(zhàn)及應(yīng)對(duì)1季節(jié)性流感疫苗開(kāi)發(fā)趨勢(shì)2通用流感疫苗的研究進(jìn)展3義翹神州整體解決方案及相關(guān)案例分享4流感疫苗開(kāi)發(fā)遇到的挑戰(zhàn)01義翹神州流感疫苗開(kāi)發(fā)遇到的挑戰(zhàn)病毒變異流感病毒的抗原漂移和基因變異快疫苗株與流行株之間存在抗原不匹配的風(fēng)險(xiǎn)流感疫苗有效性特殊群體（>65歲以上老人），疫苗的有效性不夠理想流感疫苗保護(hù)的持久性有待提高流感疫苗保護(hù)的廣泛性弱義翹神州/roadmap應(yīng)對(duì)病毒變異挑戰(zhàn)的策略改進(jìn)監(jiān)測(cè)和數(shù)據(jù)共享系統(tǒng)改進(jìn)計(jì)算方法和建模預(yù)測(cè)疫苗株的有效性/flu/pandemic-resources/monitoring/irat-virus-summaries.html義翹神州深入研究基礎(chǔ)免疫學(xué)及影響免疫保護(hù)的相關(guān)因素提升檢測(cè)技術(shù)，以利于開(kāi)展大規(guī)模免疫學(xué)研究B細(xì)胞與保護(hù)性免疫反應(yīng)研究提升對(duì)免疫穩(wěn)態(tài)及整個(gè)免疫系統(tǒng)協(xié)同作用機(jī)制的科學(xué)認(rèn)知疫苗接種后免疫反應(yīng)粘膜免疫研究開(kāi)發(fā)新型流感疫苗保護(hù)性研究方法義翹神州應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略優(yōu)化疫苗研究模型優(yōu)化動(dòng)物模型開(kāi)發(fā)預(yù)先暴露動(dòng)物模型評(píng)估不同動(dòng)物模型的價(jià)值，如豬、馬開(kāi)發(fā)新型動(dòng)物模型進(jìn)一步開(kāi)發(fā)和完善CHIVIM感染模型義翹神州開(kāi)發(fā)創(chuàng)新的流感疫苗制備技術(shù)平臺(tái)——mRNA疫苗技術(shù)應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略Doi:

10.1016/j.ymthe.2022.02.016義翹神州序列設(shè)計(jì)遞送系統(tǒng)開(kāi)發(fā)創(chuàng)新的流感疫苗制備技術(shù)平臺(tái)——VLP疫苗技術(shù)應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略義翹神州doi:10.1186/s12951-021-00806-7佐劑穩(wěn)定性開(kāi)發(fā)創(chuàng)新的流感疫苗制備技術(shù)平臺(tái)——病毒載體疫苗應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略義翹神州AVisualAidtoViralInfectionandVaccineProduction-LozierInstitute載體類型預(yù)先存在的免疫安全性應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略優(yōu)化季節(jié)性流感疫苗縮短疫苗滯后期確定優(yōu)化疫苗有效性的策略和政策提高疫苗預(yù)防重癥疾病的能力評(píng)估新佐劑作用神經(jīng)氨酸（NA）在疫苗有效性和免疫原性方面的作用義翹神州應(yīng)對(duì)流感疫苗有效性挑戰(zhàn)的策略開(kāi)發(fā)保護(hù)作用廣泛或通用的流感疫苗（UniversalInfluenzaVaccines）確定候選者保護(hù)性廣泛或通用持久保護(hù)靶向病毒保守區(qū)域建立多種有效的篩選方法義翹神州季節(jié)性流感疫苗開(kāi)發(fā)趨勢(shì)02義翹神州已獲批季節(jié)性流感疫苗株的類型目前，全球批準(zhǔn)的流感疫苗主要有三種類型：滅活疫苗、減毒活疫苗和重組疫苗義翹神州doi:10.1186/s12929-020-0626-6季節(jié)性流感疫苗株的組分每年，WHO會(huì)公布下一流感季的疫苗株組分，含有甲型H1N1和H3N2及乙型流感病毒，以“三價(jià)”或“四價(jià)”制劑生產(chǎn)。Recommendationsannouncedforinfluenzavaccinecompositionforthe2024-2025northernhemisphereinfluenzaseasonRecommended

composition

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Egg-basedvaccinesanA/Victoria/4897/2022(H1N1)pdm09-likevirus;anA/Thailand/8/2022(H3N2)-likevirus;andaB/Austria/1359417/2021(B/Victorialineage)-likevirus.Cellculture-orrecombinant-basedvaccinesanA/Wisconsin/67/2022(H1N1)pdm09-likevirus;anA/Massachusetts/18/2022(H3N2)-likevirus;andaB/Austria/1359417/2021(B/Victorialineage)-likevirus.Forquadrivalentegg-orcellculture-basedorrecombinantvaccines：aB/Phuket/3073/2013(B/Yamagatalineage)-likevirus.

義翹神州季節(jié)性流感疫苗開(kāi)發(fā)趨勢(shì)開(kāi)發(fā)新的技術(shù)平臺(tái)——縮短疫苗開(kāi)發(fā)時(shí)間，提高疫苗效果Developer:Moderna(US);Name:mRNA-1010;Stage:inPhase3phase1/2phase3免疫原性：對(duì)流感A型病毒具有較強(qiáng)免疫原性，對(duì)B型流感未達(dá)到非劣效標(biāo)準(zhǔn)。安全性：可接受/10.1038/s41467-023-39376-7NEWSRELEASEfromModernaP303數(shù)據(jù)義翹神州季節(jié)性流感疫苗開(kāi)發(fā)趨勢(shì)粘膜免疫途徑的探索感霧?凍干鼻噴流感減毒活疫苗（長(zhǎng)春百克）FluMist?

Quadrivalent（阿斯利康）LAIV通過(guò)鼻腔給藥，刺激上呼吸道的粘膜免疫反應(yīng)，誘導(dǎo)產(chǎn)生IgA抗體，在粘膜表面提供保護(hù)。doi:10.1371/journal.pone.0085582.

eCollection2014.義翹神州通用流感疫苗開(kāi)發(fā)趨勢(shì)03義翹神州通用流感疫苗研究進(jìn)展未來(lái)流感疫苗開(kāi)發(fā)的方向是開(kāi)發(fā)通用流感疫苗，可以覆蓋不同流感亞型，應(yīng)對(duì)流感的快速變異。UNIVERSALINFLUENZAVACCINETECHNOLOGYLANDSCAPE(byIVR)義翹神州通用流感疫苗研究的靶點(diǎn)和方向義翹神州doi:10.3389/fimmu.2021.711997基于HA設(shè)計(jì)的通用疫苗高糖基化HA，相對(duì)保守去掉HA頭部，僅保留有免疫原性的莖部LAH片段疫苗：HA莖部最保守區(qū)域嵌合HA疫苗：如H1HA莖部+禽流感頭部“馬賽克”HA疫苗：HA保守莖部+頭部誘導(dǎo)特異性交叉反應(yīng)抗體通用流感疫苗研究的靶點(diǎn)和方向義翹神州基于NA設(shè)計(jì)的通用疫苗廣泛保護(hù)性抗體的靶點(diǎn)奧司他韋、扎那米韋等抗病毒藥物的關(guān)鍵靶點(diǎn)doi:10.3389/fmicb.2020.00135基于M2e設(shè)計(jì)的通用疫苗高度保守抗體具有特異性基于內(nèi)部蛋白設(shè)計(jì)的通用疫苗NP、M1高度保守增強(qiáng)T細(xì)胞的交叉反應(yīng)通用流感疫苗開(kāi)發(fā)平臺(tái)/10.3390/v14081684義翹神州VLP平臺(tái)納米顆粒平臺(tái)流感病毒的HA和鐵蛋白自組裝成納米顆粒病毒載體平臺(tái)帶有所需抗原基因的腺病毒基因組序列可生成表達(dá)抗原的腺病毒載體基于核酸平臺(tái)DNA疫苗，構(gòu)建攜帶所需免疫原基因質(zhì)mRNA疫苗，代表免疫原的mRNA被配制流感病毒的HA、NA和M基因共表達(dá)產(chǎn)生VLPInfluenzaVirus-疫苗進(jìn)展VaccineNameDeveloper/LocationPlatformR&DStatusPhaseMultimeric-001(M-001)BiondVaxPharmaceuticals(Israel)RecombinantproteinsInactivePhase3QuadrivalentVLP(QVLP)Medicago(Canada)Virus-likeparticles(VLP)InactivePhase3Nano-Flu(qNIV)Novavax(US),EmergentBioSolutions(US)Non-VLPnanoparticlesActivePhase3ModifiedmRNAvaccinePfizer(US),BioNTech(Germany)Nucleicacid-basedActivePhase3mRNA-1010Moderna(US)Nucleicacid-basedActivePhase3FLU-vConserVBioscience(UK),Imutex(UK)RecombinantproteinsActivePhase2deltaFLUVivaldiBiosciences(US)Influenzavirus-basedActivePhase2M2SRFluGen(US)Influenzavirus-basedActivePhase2MVA-NP+M1(VTP-100)Vaccitech(UK)Virus-vectoredInactivePhase2NasoVAXAltimmune(US)Virus-vectoredInactivePhase2VXA-A1.1oraltabletVaxart(US)Virus-vectoredActivePhase2CICVaccineNovavax(US)Non-VLPnanoparticlesActivePhase2OVX836Osivax(France)Non-VLPnanoparticlesActivePhase2mRNA-1020andmRNA-1030Moderna(US)Nucleicacid-basedActivePhase2UNIVERSALINFLUENZAVACCINETECHNOLOGYLANDSCAPE(byIVR)義翹神州整體解決方案及相關(guān)案例分享04義翹神州義翹神州擁有全球領(lǐng)先的流感病毒研究試劑庫(kù)10+抗原類型HA(HA0/HA1,HA2,HA),NA,NP,M1,M2,NS1,PB1,PB2,PA630+重組蛋白產(chǎn)品高活性覆蓋熱點(diǎn)科研毒株200+抗體涵蓋廣譜HA、NP抗體中和抗體應(yīng)用驗(yàn)證廣（WB、ELISA、IHC等）60+亞型H1-H18,N1-N11,InfluenzaB330+分離株VaccineStrainsHPAIStrainsNewlyIdentifiedStrains1,500+基因及檢測(cè)試劑盒產(chǎn)品檢測(cè)試劑盒涵蓋：抗原含量檢測(cè)試劑盒滴度檢測(cè)試劑盒中和抗體檢測(cè)試劑盒義翹神州純度高HPLC驗(yàn)證生物學(xué)活性高批間穩(wěn)定性高ISO9001&ISO13485義翹神州擁有全球領(lǐng)先的流感病毒研究試劑庫(kù)RecombinantAntigensfor2015-2025InfluenzaVaccineStrainsRecombinantAntigensforEmergingPandemicStrainsWHO推薦-禽流感疫苗株義翹神州TitleYearJournalMoleculeCatalogueApplicationspeciesInitiationofAntiviralBCellImmunityReliesonInnateSignalsfromSpatiallyPositionedNKTCells2017CellHA11684-V08Hbinding(ELISA)H1N1(A/PuertoRico/8/34)Nucleoside-modifiedmRNAvaccinesinducepotentTfollicularhelperandgerminalcenterBcellresponses2018J.Exp.Med.HA11684-V08HimmunizationH1N1ASiteofVulnerabilityontheInfluenzaVirusHemagglutininHeadDomainTrimerInterface2019CellHA11085-V08BELISAandcellbasedH1N1BroaderneutralizationofCT-P27againstinfluenzaAsubtypesbycombiningtwohumanmonoclonalantibodies2020PLoSONEHA11055-V08HELISAH1N1Chemoreactive-inspireddiscoveryofinfluenzaAvirusdualinhibitortoblockhemagglutinin-mediatedadsorptionandmembranefusion2020J.Med.Chem.HA11707-V08H，11684-V08HSPRH3N2Highaffinityanti-TIM-3andanti-KIRmonoclonalantibodiesclonedfromhealthyhumanindividuals2017PLoSONEHA11053-V08HantigenInfluenzaBvirus(B/Florida/4/2006)InhibitionofinfluenzaAvirusinfectionbyginsenosides2017PLoSONEHAproteinWB

MemoryBCellActivation,BroadAnti-influenzaAntibodies,andBystanderActivationRevealedbySingle-CellTranscriptomics2020CellRepHA11683-V08HELISAH1N1部分產(chǎn)品的文章引用數(shù)據(jù)義翹神州臨床前研究流感疫苗開(kāi)發(fā)整體解決方案產(chǎn)品：重組抗原中和抗體，檢測(cè)抗體抗原含量檢測(cè)試劑盒胞因子檢測(cè)試劑盒流式抗體假病毒服務(wù)：細(xì)胞庫(kù)檢測(cè)（CHO,Vero,HEK293等）病毒清除驗(yàn)證實(shí)驗(yàn)抗原開(kāi)發(fā)服務(wù)抗體開(kāi)發(fā)服務(wù)理化及生物效價(jià)評(píng)估（滴度、中和等）生產(chǎn)質(zhì)控-疫苗生產(chǎn)工藝的研究；-免疫原性或生物效價(jià)；穩(wěn)定性研究-免疫原性；-疫苗生物效價(jià)產(chǎn)品：重組抗原中和抗體，檢測(cè)抗體細(xì)胞因子檢測(cè)試劑盒流式抗體假病毒服務(wù)：生物效價(jià)評(píng)估人源化抗體服務(wù)產(chǎn)品：重組抗原抗原含量檢測(cè)試劑盒中和抗體，檢測(cè)抗體假病毒核酸酶核酸酶殘留檢測(cè)試劑盒服務(wù)：生物效價(jià)評(píng)估人源化抗體服務(wù)理化及生物效價(jià)評(píng)估（SEC-MALS，SPR，BLI等）-抗原、抗體、生物效力的檢測(cè)；-雜質(zhì)、殘留檢測(cè)臨床研究義翹神州具有活性驗(yàn)證數(shù)據(jù)特色產(chǎn)品及服務(wù)——流感BioactiveHAAntigensHA:HemagglutinationActivityH1N1,A/swine/Shandong/1207/2016(Cat:40651-V08H)H7N9,A/Anhui/1/2013

(Cat:40103-V08B)HA:BindingActivitytoSialicAcidBLI:KD=18.4nM(Cat:40116-V08B)NA:EnzymaticActivityH1N1,A/Brisbane/02/2018(Cat:40767-V08B)MeasuredNA’sabilitytocleave2'-(4-Methylumbelliferyl)-α-D-N-acetylneuraminicacid.Thespecificactivityis40296pmoles/min/μg.H1N1,A/Brisbane/02/2018(Cat:40569-V08B)MeasuredNA’sabilitytocleave2'-(4-Methylumbelliferyl)-α-D-N-acetylneuraminicacid.Thespecificactivityis29781pmoles/min/μg.義翹神州特色產(chǎn)品及服務(wù)——流感更接近天然：流感HA三聚體蛋白Thepurityismorethan95%.TheMWisaround225kDa.SEC-MALSImmobilizedrecombinantHAprotein(Cat:40938-V08H2)

at5μg/mL(100μL/well)canbindRecombinantHumanGalectin-1/LGALS1Protein

(Cat:10290-HNAE),theEC50

is120-350ng/mL.ImmobilizedrecombinantHAProtein(Cat:40938-V08H2)

at1μg/mL(100μL/well)canbindantibodytargetstheHAstemregionofH1N1,theEC50

is4ng/mL-12ng/mL.ActivityInfluenzaAH1N1(A/Victoria/4897/2022)Hemagglutinin/HATrimerProtein(HisTag)(HPLC-verified)義翹神州特色產(chǎn)品及服務(wù)——流感流感廣譜Hemagglutinin/HA抗體H1N1廣譜HA抗體：86001-RM01H3N2廣譜HA抗體：11056-MM03InfluenzaB廣譜HA抗體：11053-R004編號(hào)蛋白貨號(hào)亞型毒株疫苗株年份86001-RM0111056-MM0311053-R004140938-V08HH1N1A/Victoria/4897/20222023-2024+++--240940-V08HA/Wisconsin/67/20222023-2024+++--340787-V08H(A/Wisconsin/588/2019)/(A/Victoria/2570/2019)2022-2023+++--140859-V08BH3N2A/Darwin/9/20212023-2024,2022-2023++++++-240868-V08BA/Darwin/6/20212022-2023++++++-340789-V08HA/Cambodia/e0826360/20202021-2022++++++-140498-V08BInfluenzaBB/PHUKET/3073/20132015-2024--+++240862-V08HB/Austria/1359417/20212023-2024,2022-2023--+++340722-V08HB/Washington/02/20192022-2023,2021-2022,2020-2021--+++廣譜流感HA抗體義翹神州特色產(chǎn)品及服務(wù)——流感HA試劑盒（經(jīng)濟(jì)型+即用型），滿足不同檢測(cè)通量需求NP經(jīng)濟(jì)型試劑盒，靈活搭配不同標(biāo)準(zhǔn)品，滿足不同毒株定量需求貨號(hào)抗原種屬分子線性范圍(pg/mL)靈敏度(pg/mL)KIT11055H1N1HA31.25-200014.71KIT11684H1N1HA62.5-400018.5KIT11056H3N2HA781.25-50000263.49KIT11714H4N6HA62.5-400016KIT11048H5N1HA125-800089.7KIT40103H7N9HA15.6-10004.9KIT40104H7N9HA15.6-10003KIT11229H9N2HA78.13-50006.9KIT11053InfluenzaBHA109.38-700025.54貨號(hào)抗原種屬分子線性范圍(pg/mL)靈敏度(pg/mL)SEK001H1N1HA31.25-200031.25SEK11684H1N1HA28.13-400028.13SEK11056H3N2HA390.63-25000390.63SEKA002H5N1HA125-8000125SEK40103H7N9HA62.5-400062.5SEK11229H9N2HA156-10000156SEK11053InfluenzaBHA78.13-500078.13SEK004H1N1NP62.5-400062.5SEK006H3N2NP234.4-15000234.4SEK005InfluenzaBNP39.06-250039.06SEK007InfluenzaBNP156.25-8000156.25即用型經(jīng)濟(jì)型義翹