WO2018148499A1 - Séquences peptidiques de flavivirus, épitopes, et procédés et utilisations de ceux-ci - Google Patents

Séquences peptidiques de flavivirus, épitopes, et procédés et utilisations de ceux-ci Download PDF

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Publication number
WO2018148499A1
WO2018148499A1 PCT/US2018/017554 US2018017554W WO2018148499A1 WO 2018148499 A1 WO2018148499 A1 WO 2018148499A1 US 2018017554 W US2018017554 W US 2018017554W WO 2018148499 A1 WO2018148499 A1 WO 2018148499A1
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Prior art keywords
zikv
mice
cells
denv
cell
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PCT/US2018/017554
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English (en)
Inventor
Sujan Shresta
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La Jolla Institute For Allergy And Immunology
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Publication of WO2018148499A1 publication Critical patent/WO2018148499A1/fr
Priority to US16/537,447 priority Critical patent/US11806393B2/en
Priority to US18/368,949 priority patent/US20240156939A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C07K14/08—RNA viruses
    • C07K14/18—Togaviridae; Flaviviridae
    • C07K14/1816—Flaviviridae, e.g. pestivirus, mucosal disease virus, bovine viral diarrhoea virus, classical swine fever virus (hog cholera virus), border disease virus
    • C07K14/1825—Flaviviruses or Group B arboviruses, e.g. yellow fever virus, japanese encephalitis, tick-borne encephalitis, dengue
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24111—Flavivirus, e.g. yellow fever virus, dengue, JEV
    • C12N2770/24134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/18—Togaviridae; Flaviviridae
    • G01N2333/183—Flaviviridae, e.g. pestivirus, mucosal disease virus, bovine viral diarrhoea virus, classical swine fever virus (hog cholera virus) or border disease virus
    • G01N2333/185—Flaviviruses or Group B arboviruses, e.g. yellow fever virus, japanese encephalitis, tick-borne encephalitis, dengue
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This genus includes the West (ZIKV) and several other viruses which may ca n u c s e e ph en al c i e ti p s h ( a T li B ti E s, ) virus, yellow fever virus, Zika virus (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus as (P wCeVll) a,s an indse Pcat-rsrapecific flaviviruses (PaRV).
  • Flaviviruses are globally emerging flaviviruses are maintained in animal reservoirs fo inrm nat oufre en ancedp ahraelit tirsan or hemorrhagic fever. Most through the bite of an infected mosquito or tick. Other virus transsmmiisttseiodn to ro huutmesan csan pr iinmclaurdilye
  • c leb e l s of ZIKA infection have no symptoms, but when present they are usually conju oer d joeningtu peai fne,v nera,u asenad, v moamyit cinaugs,e or fe lovsesr, o rfa asphp,e hteitaed.ache, pain behind the eyes, [ m00ic7r]ocepha Flyu hrtahser b,ee an c caounsafilrm reeldati ionn tshheip 20 b1e5tw
  • Vaccines are currently available for only yellow fever and Japanese and TBE; however, heavwe v sahcociwnnes t fhoart d felanvgivuieru asneds, W esepstec Niaillley a dreen ingu celin viicrauls tr hiaalss in humans.
  • many studies response during the infection (Diamo the ability to inhibit the innate immune 30; Jones M, Dav nd MS (September 2009), J.
  • Interferon Cytokine Res.29 (9): 521– virus has many nidosonnst Aru,ct Huribable prtro Lt,ei ents al t.h (aMta ayllo 2w00 t5h)e. J i.nh Vibiriotli.o 7n9 o (f9) v:a 5ri4o1u4–20). Indeed, the dengue immune system response. Disease diagnosis can be dif s mediators of the innate genetically closely related ficult as all flaviviruses are antigenically and main approach to disease.
  • o csom emprbisoidniged at l aenadst o bnroea isdolylate ddes pceripbteidde a hnedre ainn, ac thceept pabrelese cnatrri deirsc olros duilrueen rte,l tates to a
  • p oeprt aidte le caostm 9p8r%is,in ogr a ant l aemasitn 9o9% ac,id or se 1q0u0e%nc iede wnhtiiccahl i tso at least 95%, or at least 96%, ohre a att l leeaasstt
  • an amino acid sequence which is 95% identical w he isolated peptide may comprise NO: 1 and at least a second peptide i ith the amino acid sequence set forth in SEQ ID acid sequence which n the plurality of the isolated peptide may comprise an amino various possibilities o ifs h 9a8v%ing id deinfftiecraeln wti pthep tthidee a smeqinuoen acceid in se aqu pelunrcaelit syet o ffo prethpt iinde SsEQ ID NO: 2.
  • the antigenic component may contain cells producing or rel xample, comprising an amino acid sequence which is at least 95 easing at least one peptide 98%, or at least 99%, or 100% identic %, or at least 96%, or at least 97%, or at least NO: 1 to SEQ ID NO: 93.
  • h reu i eca r c hch a tpi is pe dpiftfiedreen otf t fhroem plu ornaleity an ooft thheer, is aosla dteedsc preibpetdide ab coomvepr wisitehs described methods, for example oenustic fo orr u psreev menatyat bivee t voac imcinpaletimonen atga ainnyst o an fela ovfiv tirhues.
  • the m rises contacting the sample with the composition of the cell response, and detectin e g th t o h d e a p l r s e o se c n o c m e p o r r is a e b s s p e r n o c c e es o s f in t g he th T e c s e am ll p re le sp t o o n d se e .
  • the method may further include causing a transmission of posed to the flavivirus.
  • In expert may include a smartphone, a tablet, a ge ciated with the particular medical computing device and o tthheer e sluecitt neral purpose computer and/or any other suitable message and/or or any arbolneic ele ncotrtiofniciacti moness daagtea.
  • the present disclosure further relates to a the methioodn o cfo tm r sustaining an immune response against a flavivirus in a subject, composit hepr pirseinsgent c doinstcaloctsiunrge.
  • T cells of the subject with an effective amount of the [ a 0 m 01 o 7 u ] nt of th In e c o o n m e p n o o s n it - io lim n i t t o in t g he em su b b o je d c i t m .
  • the contacting includes administrating the effective [ t0h0e18 e]ffective In am onoeun nto onf-li tmheitin cogm empobsoitdioimn,en ant,d th aedm coinntisatcrtaitning includes contacting T cells ex vivo with The method may further comprise expansion o g the contacted T cells to the subject. contacted T cells to the subject. f the T cells in vitro prior to administrating the 4
  • i ats f,la tvhievir huesre inin a d seusbcrjeibcetd m mayet ahffoodrd of on ined tuoc oinbgt,ai ennh atan lecaisntg o,n oer i rnehdiubciet f tlhaveiv rus titer, increase or stimulate flavivirus clearance, reduce or a imruosu pnrto oliffe ara ftliaovni,v rireudsuc pero otrei innh oibri tth inec armeaoseusnt in flavivirus titer or flavivirus proliferation, inhibit synthesis of a flavivirus protein or a flavivirus nucleic of ac aid f.la .vivirus nucleic acid, or reduce or [ o0r02 su0]staining
  • the flavivirus is a Zika virus.
  • the flavivirus is a Dengue virus.
  • composition of the present disclosure may include an acceptoabrele a ccacrerpietarb mleay ca brreie srel seecletecdted fro frmom go tlhde p aacrcteicpletasb,l sete crarriers described herein.
  • acceptoabrele a ccacrerpietarb mleay ca brreie srel seecletecdted fro frmom go tlhde p aacrcteicpletasb,l sete crarriers described herein.
  • buffered solutions buffered solutions.
  • Carriers may inc ile water, saline, glucose, dextrose, or stabilizers (i lude auxiliary agents including, but not limited to, diluents, buffering age.en.t,s, s vuigsacrossit ayn ednh aamnicniong a acdiddsit)i,ve psr,e csoerlovrasti avnesd, th weet litkineg. agents, emulsifying agents, pH 5
  • n v i san enc stlu , s mde uacy on h be aes ( aPoimfcmoe Lracbiaollryat aotownilsa,b Dleet arso,it f,o Mric ehx.a)m; Mpleer,ck Fr Aeudnjudv’san Itn 6c5om (Mpleertcek A anddjuvant and Cbolmep aledtjeuv Aandtjsuva anret irluminum salts such as aluminum hydroxide gel (alum) or alu Company, Inc., Rahway, N.J.); deorniv oatriz zeidnc p;o anlys inacscohluabrildee ssu;s ppoelnyspiohno of acylated tyrosine acylatmedin suumgar psh;o csapt
  • TLR-4 S toulilt-albiklee mim type 4 (TLR-4) agonists (e.g., monophosphoryl lipid A (MPL), synthetic lipid A, lipid A CpGet oiclsigo osr, a lnipaloopgos)ly,s aalcucmhainriudme ( sLalPtsS,) cy otfok girnaems,-n saepgaotnivines, b macuterraima,yl p doilpypephtoidspeh (aMzeDnP) derivatives, virosomes, cochleates, poly(lactide-co-glycolides) (PLG) microparti es, emulsions, microparticles, liposomes, oil-in-water emulsions, MF59, a cles, poloxamer particles, adjuvants are not bacterial
  • adjuvants which stimulate a Th1 type response sunch may include include certain synthetic polymers such as poly amino as 3DMPL or QS21. Adjuvants may also saponin, paraffin oil, and muramyl dipeptide. Adjuv acids and co-polymers of amino acids, immunomodulatory molecules encoded in a co- ants also encompass genetic adjuvants such as coinoculated DNA can be in the same plasmid inoculated DNA, or as CpG oligonucleotides. The DNA vector. The reader can refer to Vacc construct as the plasmid immunogen or in a separate of suitable adjuvant.
  • compositions of the present disclosure may be formulated for parenteral nctteiodn i,n e u.gn.i,t d boysa bgoelu fsorm in,je ec.tgio.,n in o arm cpoonutliensu oorus in i mnfuulstiio-dno.se Fo cromntualianteions for an added preservative.
  • the compositions may take such forms as suspension rs, with emulsions in oily or aqueous vehicles, and may contain formulatory a s, solutions or stabilizing and/or dispersing agenet,s e..
  • composition of the present disclosure may be administered in the form suspensions may be foramtiuolna,te sduc ahcco asrd sitnegril teo i tnejcehcntaiqbulees aq kuneoowuns i onr th oelea agrtin uosuinsg su suspiteanbsleio dnis. These or wetting agents and suspending agents.
  • the sterile injectable prepara spersing injectable solutions or suspensions in non-toxic parente tions may also be sterile may be given parenterally, for examp rally-acceptable diluents or solvents. They injection, by infusion o le intravenously, intramuscularly or sub-cutaneously by amount of each of the crom pepro onse.n Stusi itnab tlhee d coosmagpeossi wtioilnl, v tahrey, d deesipreednd eifnfgec utp (sohnor ftac otro lrosn sgu tcehrm as), t thhee
  • the liquid antigen is freeze dried in the presence of agen xposure during drying.
  • composition of the present disclosure may be formulated m cuti fdor (e r.egc.o anqsuteitouutsio fnor wmituhla wtioatne)r, o e.rg.
  • o,t ahser sy sruuiptasb oler v suehspicelnes bioenfos,re or us me.ay Su bceh p lriqeuseidnted as a drug suay be prepared by conventional means with pharmaceutically acceptable ad preparations agespnetsnd (ein.gg., ag leecnitthsi (ne.g o.r, s aocrabciitao);l s nyornu-pa,q cueeloluuloss vee dheicrilvatives or hydrogenated edible fadtisti)v;e esmu sulscifhyin ags vegetable oils); and preservatives (e.gg., ag leecnitthsi (ne.g o.r, s aocrabciitao);l s n
  • es e.g., almond oil, oily esters, or fractionated pharmaceutical compositi g., methyl or propyl-p-hydroxybenzoates or sorbic acid.
  • the conventional means wions may take the form of, for example, tablets or capsules prepared by pregelatinized maize statrhch, ph paorlmyvainceyult picyarlrlyoli adcocneept oabrle hy edxrcoixpyiepnrotspy slu mcheth asylc beilnludloinsge); ag fiellnetrss ( (ee..gg.., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g , stearate, talc or silica); disintegrants (e.g., potato starch or sodium star ., magnesium (e.g., sodium lauryl sulphate).
  • the tablets may be coated by methods wcehll- gklyncoowlante i)n; o thre w aerttt.ing agents [ r0e0s3p5ir]atory ( We.gh.e nraesa tlh)e mu cocomspa,o tsyitpioicnally of it t ishe for pmreusleantet disclosure is intended for delivery to the an aerosol or nasal drops, or alternatively, d as an aqueous solution for administration as passage.
  • Compositions for admi as a dry powder e.g.
  • nasal drops may contain one or more excipients of the tonicity adjusting agents, su bcuhffe croinmgpo agsietniotsn,s, an fodr t ehxeam likpel.e V pirsecsoesrivtayti avgees,nt vsis ccaonsit bye ad mjuicsrtoincgrys atgaelnlintse, 8
  • r eidon isn fo surc ahdm coinmisptroastiitoionn ass, d foryr trizeeha clohsaer,a acntedri xsytilcitso.l.
  • Bulking and powder flow and size agents may app inrcolpurdieate m paonwnidtoerl, fl souwcro ansed, [ e0
  • the herein described methods and/or kits may skide, a multi-well pla a membrane, a chip, a disk, a test strip, a filter, a microsphere, a usiellded wh iner t te, an optical fiber, and the like, or any other variant available to the person t eh ae s aarmtp wlieth toou bte d teepstaerdtin cgan fr boem ad tdheed p drerosepnwtis deis tcolo asu sarem.
  • p Fleor ap epxalimcaptiloe,n a pa tedst pr setsriepnt m oany t bhe leest strip, and the presence of at least an isolated peptide compris
  • p t is m idaednetic baals teod t
  • su ide As discussed pepmtiudneo odfet tehceti polnur maleittyho odf t whheic ishol dateetdec ptsep ptriedseen ccoe of a plurality ofc thhe te issotl sattreipd m peapyti mdea,k weh uesree o efac anh different from one another, as describ mprises a respective amino acid sequence which is immunodetection method may include an imemd above with respect to the composition.
  • Aodsi umseendt, he threein h,e threein ter dmesc“rpibacekdag kit may include at least one solid matrix or material such as glass, plastic, paper, fiber, f ed” can refer to the use of a fixed limits the at least one detection reagen oil and the like, capable of holding within include the at least one detecting ag t.
  • the kit may milligram quantities of the at ent“packaged” in a glass vial used to contain microgram or may include the at least one detecting agent.
  • the kit microgram quant least one detecting agent“packaged” in a microtiter plate well to which non-li ities of the at least one detecting agent has been operatively affixed.
  • micropmairttinicgles e emnbtroadpipmeedn wt,ith thine a k pitor mouasy m inemclubdrae
  • the kit may include the at least one detecting agent directly l , b t e es r t e s a t d r i i l p y o re r co d g ip n s i t z i e c d k, b e y tc t . h w os h e ic s h ki c ll o e n d ta in cts th t i h s e ar s t am wi p th le ou fl t ui d d e . p M ar a ti n n y g o fr t o h m er
  • the herein described subject can be a mammal, preferably a human.
  • Elements of one embodiment can be present invention wereill e bmebcoodmimee anptpsar wenittho tout th fuorsther mention.
  • R 2 fl/ A fl m t o o use F m ig. ode 2 l C of s Z ho IK w V e in xe fe m ct p io la n ry in n a o c n c - o li r m da it n in ce g w r it e h su a lt n s obtained with a present disclosure; embodiment of the [ o 0 f 04 Z 3 I ] KV ep F i i t g o . p 3
  • Fig.4A to Fig.4F show exemplary non-limiting results of polyfunctional phenotype of emKboVdim epeintotp oef- tshpeec pirfeicsen CtD di8s+clo Tsur cee;lls in LysMCre+IFNARfl/fl mice in accordance with an
  • e nTt o d show graphs that illustrate non-limiting results of ZIKV burden in f am thse a pnredse tnhtei dris fceltoussuerse; on day 2 and 3 after ZIKV infection in [ e 0 p 0 i 5 to 7 p ] e-spe F ci i f g ic .1 C 8 D A 8 + to T F c i e g l .
  • u m to Fig.22L show graphs that illustrate non-limiting results of the effect of a neb Iinfneadr1 C-/-D d4a + m asn idn C acDco8r + d Tan cceell w diethpl aentio enm obnod ZimIKenVt v oifra thle bu prrdeesenn itn d nisocnlo-ismurme;une [ f 0 ro 06 m 2] n Ton c-eilm Fi
  • the flavivirus vaccine, diagnosis assay, and/or treatment approach [ r 0 e 0 la 6 t 8 e ] s to D I E n N o V n .
  • the flavivirus vaccine, diagnosis assay, and/or treatment approach [ r 0 e 0 la 6 t 9 e ] s to ZI I K n V on a e nd em D b E o N di V m . ent, the flavivirus vaccine, diagnosis assay, and/or treatment approach
  • ZIKV is a positive-sense, single-stranded, enveloped RNA flavivirus that was first m be i e lldat
  • the virus i.e., serotypes
  • serotypes the virus (i.e., serotypes)
  • MHC I foreign peptides identifi bility complex class I
  • nucleic acid is used sequences are displayed herein in the conventional 5’-3’e ooriteidneta,ti aonnd. polynucleotide.
  • nucleotide [ r0e0fe8r3] to a po Tlyhmee trer omfs am“pinooly apceipdt rideesi,d”u“eps.ep Tthidee t”er and“protein” are used interchangeably herein to m as o w re el a l m as ino to ac n i a d tu r r e a s l i l d y u o e c i c s u a r n ri analog or mimetic omfs a a cpoprrlyes tpoo anmdiinngo n aactidur palolylylyly omcecrusrr ining wh amichin oon aeci odr, addition of carbohy ng amino acid polymers.
  • Polypeptides can be modified, e.g., by the “protein” include gdlyractoepr roesteidinuse,s a tos f woermll a gslyc noopnr-ogtleyicnosp.r Tohteein tse.rm Tshe“p poolylpypepeptitdide,e” s“epqeupetnidcee”s and displayed herein in the conventional N-terminal to C-terminal orientation.
  • Naturally occurring amino acids are those encoded by naturally well as those amino acids that are later modified, e.g., hydroxypr the genetic code, as phosphoserine.
  • amino acid analogs oline, carboxyglutamate, and O- chemical structure as a naturally occurri refers to compounds that have the same basic hydrogen, a carboxyl group, an a ng amino acid, i.e., an .alpha. carbon that is bound to a methionine sulfoxide, meth mino group, and an R group, e.g., homoserine, norleucine, (e.g., norleucine) ionine, and methyl sulfonium.
  • R group e.g., homoserine, norleucine, (e.g., norleucine) ionine, and methyl sulfonium.
  • Such analogs have modified R groups naturally occurrin ogr a mmoindoifie adcid p.ep Atmidein boac ackibdon meism, betuicts re rteafienrs th teo s cahmeem bicaaslic co cmhepmoiucnalds str tuhcattu hreav aes a a
  • nucleic acid does not encode an amino aci dentical amino acid sequences, or where Specifically, degenerate codon d sequence, to essentially identical sequences.
  • t dheiordxyi pnoossiitnioen re o substitutions may be achieved by generating sequences in which the sifdu oense (B oartz mero erte a sl.e,l Necutecdleic (o Arc aidll) R ceos.d 1o9n:s50 i8s1 s (u1b9s9t1it)u;t Oedht wsuitkha e mti axle.,d J-base and/or 260:2605-2608 (1985); Rossolini et al., Mol. Cell. Probes 8:91-98 (1 . Biol. Chem.
  • the codons GCA GC identical nucleic acids encode any given protein. every position where an alan C, GCG and GCU all encode the amino acid alanine.
  • the codon can be S vaurcih he corresponding codons described without altering the encoded polypeptide.
  • a polymerase e.g., a DNA polymerase.
  • ences may be depicted in the form of a sequence listing, [ r0
  • n e d xp tr r a e n ss s i l on refers to the transcription of a gene to produce the (i.e., a peptide, polypeptide, or proatteioinn).
  • the te strain are alleviated or completely disease or s rm“preventing” refers to a process by which an infection or a delayed. ymptoms of an infection or a disease associated with a flavivirus are obstructed or [ c 0 o 0 m 95 p ] ound t T ha h t e ca e n xp b r e e a ss d i m on ini “ st a e n red ac t c o ep a t s a u b b le jec c t a w rr i i t e h r o ut m si a g y nif r i e c f a e n r t a to dve a rse ve e h f i f c
  • adjuvants are believ w an adjuvant (humoral and/or cellular response) by ed to enhance the immune response strongly immunogenic in their own right an sldow arlye b reellieeavseindg to th fuenc atniotinge sny,ne wrghiisletica oltlhy.er adjuvants are
  • Generally plate are coated with captu the membrane surfaces in a 96-well PVDF-membrane microtiter D se u ed ri e n d g i t n h t e o c t e h l e l i re antibody that binds a specific epitope of the cytokine being assayed.
  • cytokine As d in the specific cells are activated, they release the cytokine, which is captured the antigen- surface by the immobilized antibody.
  • the cytokine is thus“cap directly on the membrane surrounding the secreting cell, before it has a chance to diff tured” in the area directly degraded by proteases and bound by receptors on bystanuse into the culture media, or to be v acistuivaalitzeed t cheell.
  • immobilized cytokine as an ImmunoSpot; essednetrial cleylls th.e Su sbecsreeqtuoernyt fo doettepcrtiniotn of ste thpes
  • T ohfe m seea tseurrmemse innct,lu adned b inoctlhud qeua dnettietramtivinein agnd if/ aonr e qlueamlietanttiv is determinations, which both require sample processing and transformation steps of th e sample. Assessing may be relative or absolute.
  • tr r e o a m tm o e te nt o . r F s o t r im e u x l a a m te p a le n , ti- th fl e avi i v m ir m us un a e cti s v y i s t t y em of c im ell m s u m ne ay sy in st c e l m ude ce T lls c i e n lls a , [ a0ll0o1w01 t]he co Tmhpeo enxepnrtes osrio cnom“tphoersapeutically effective amount” may include the amount necessary to ca ition to which it refers to perform its immunological role without T
  • i t u hich the component or composition is administered.
  • i osned be oirng th tere caotemdp, tohseiti toynpe to an bde a agdem ofin tihstered will vary treated, the mode of administration, as well as the other ingredients in the compositione. subject to be EXAMPLES
  • Example 1 refers to the results shown in Fig.1A to Fig.8.
  • Example 1 can be summarized as follows:
  • [ f0o0r10 E7m]ergin ZgIK ViVru sstersai annsd M ARr7b66 and FSS13025 were obtained from the World Reference Center sentinel monkey rhesus (766) ino evaisruts Aesfri (cWaR (DCiEckV,A 19).52 M).R S7in66c,e A thfirsic iasonla ltinioena,ge th wea MsR is7o6l6ate isdol fartoem ha a b s weaesn is poalsastaegde idn o 2v0e1r01 f0r0om tim aes C ianm mboicdeia unsin pged iniattrraicce craesbera (lH ineaoncgul eattio alns (Dick, 1952).
  • ZIKV FSS13025 low number of times.
  • MR766 and FSS13025 were cultur ., 2012) and has been passaged a cells as described previously (Prestwoo ed using C6/36 Aedes albopictus mosquito 10 days after infect d et al., 2008).
  • Virus was harvested from cell supernatants 7- ultrac ion, followed by clarification via centrifugation, and concentration via hamsteenrtr kiifdungeaytio (BnH aKs) p-r2e1vi coeulls-lbya dseedsc froibceuds-f (oPrrmesitnwgo aosdsa eyt ( aFlF.,A 2)0.1 Z2aI).
  • mice were purchased from the Jackson laboratories, and LysMCre+IFNARfl/fl n -/- U C n 5 iv 7 e B r L si / ty 6 Sc m h i o ce ol o w f er M e ed b i r c e i d ne a A t n L im a al Jo F l a la cil I it n ie s s ti .
  • n s th w is ith stu 20 d 0 y ⁇ an l d of a Z ll I i K n V viv i o n i 1 n 0 fe % ct F io B n S s / w P e B r S e r weu
  • CMC carboxymethyl cellulose
  • h ee 66 and FSS13025 was selected to identify s riz peedp.tides that overlapped by 11 amino acids 1.4 Peptide synthesis
  • a CD t8+ T cells were isolated by magnetic bead positive selection (Miltenyi Biotec, p (I r m es m en o t b in il g on cTeMll - sot

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Abstract

La présente invention concerne une composition de matière, des procédés et l'utilisation de la composition de matière en rapport avec des peptides et épitopes de flavivirus, par exemple à des fins de vaccination thérapeutique ou préventive contre un flavivirus, et/ou pour induire, améliorer ou entretenir une réponse immunitaire contre un flavivirus, et/ou pour détecter une infection par un flavivirus ou une exposition à un flavivirus chez un sujet. Le flavivirus peut être, par exemple, le virus Zika et/ou le virus de la dengue.
PCT/US2018/017554 2017-02-10 2018-02-09 Séquences peptidiques de flavivirus, épitopes, et procédés et utilisations de ceux-ci WO2018148499A1 (fr)

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Cited By (2)

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WO2021127017A1 (fr) * 2019-12-16 2021-06-24 La Jolla Institute For Immunology Combinaisons de protéines de flavivirus, séquences peptidiques, épitopes et procédés et utilisations de ceux-ci
WO2021178281A1 (fr) * 2020-03-03 2021-09-10 Mayo Foundation For Medical Education And Research Polypeptides du virus zika

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US20090221005A1 (en) * 2006-03-20 2009-09-03 St Vincent's Hospital Sydney Limited Method for detecting antigen specific or mitogen-activated t cells
WO2011163628A2 (fr) * 2010-06-24 2011-12-29 La Jolla Institute For Allergy And Immunology Séquences polypeptidiques du virus de la dengue (dv), épitopes de lymphocytes t et leurs procédés et leurs utilisations
EP2853590A1 (fr) * 2012-05-22 2015-04-01 The University of Tokyo Procédé de production de lymphocytes t spécifiques d'un antigène

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US20090221005A1 (en) * 2006-03-20 2009-09-03 St Vincent's Hospital Sydney Limited Method for detecting antigen specific or mitogen-activated t cells
WO2011163628A2 (fr) * 2010-06-24 2011-12-29 La Jolla Institute For Allergy And Immunology Séquences polypeptidiques du virus de la dengue (dv), épitopes de lymphocytes t et leurs procédés et leurs utilisations
EP2853590A1 (fr) * 2012-05-22 2015-04-01 The University of Tokyo Procédé de production de lymphocytes t spécifiques d'un antigène

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JANAHI E. M. ET AL.: "In silico CD 4+, CD 8+ T- cell and B- CELL immunity associated immunogenic epitope prediction and HLA distribution analysis of Zika virus", EXCLI JOURNAL, vol. 16, 13 January 2017 (2017-01-13), pages 63 - 72, XP055537261 *
MIRZA M. U. ET AL.: "Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins", SCIENTIFIC REPORTS, vol. 6, no. 37313, 9 December 2016 (2016-12-09), pages 1 - 17, XP055537239 *
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SARMA K. ET AL.: "Immunoinformatics screening of prospective MHC class I restricted cytotoxic T- cell based epitopes in Zika virus", INTERNATIONAL JOURNAL OF CURRENT ADVANCED RESEARCH, vol. 5, no. 9, September 2016 (2016-09-01), pages 1229 - 1235, XP055537245 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021127017A1 (fr) * 2019-12-16 2021-06-24 La Jolla Institute For Immunology Combinaisons de protéines de flavivirus, séquences peptidiques, épitopes et procédés et utilisations de ceux-ci
WO2021178281A1 (fr) * 2020-03-03 2021-09-10 Mayo Foundation For Medical Education And Research Polypeptides du virus zika

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