non-human primatesandinhumans, induce potentimmuneresponses in RNA delivered byviral vectorscan using pDNA,mRNAorself-amplifying a promising riseinefficiency. Strategies local approaches todeliverpDNAby recent responses inhumans,althoughmore found toproduce insufficientantibody However, vaccinationwithpDNAwas DNA, asitismore stablethanRNA. approach focusedon intoavaccine Early effortstodevelopthis protein. leads to theencoded the expressionof (pDNA) intoskeletalmuscle of mice injection of mRNAorplasmid DNA itwhen ago wasdecades found that vaccines wastwo over conceived nucleic-acid-based approaches. some ofthelimitationsearlier nanoparticles (LNPs),whichovercomes RNA encapsulatedinsyntheticlipid platform basedonself-amplifying colleagues present anewvaccine Now, reporting in product forhumanuse. commercial a in but havenotyetresulted investigated for several decades, DNA andRNA)havebeen (both Vaccines basedonnucleicacids a next-generation vaccine? lipid nanoparticles: Self-amplifying RNAin NATURE REVIEWS REVIEWS NATURE The concept of nucleic-acid-encoded The conceptofnucleic-acid-encoded
VACCINES in vivo electroporation haveshown PNAS |
DRUG DISCOVERY , Gealland
viral replicon particles(VRPs). by thelatestviral vectortechnology, that laststwiceaslongRNAdelivery by LNPsleadstoantigenexpression gene, itwasshownthatRNAdelivery DNA-based vaccines). for factor (this was found tobearate-limiting need tocross thenuclearmembrane is eliminatedandtheRNAdoesnot cells, theriskofgenomicintegration take placeinthecytoplasmoftarget amplification andprotein expression machinery wasretained. AsRNA of interest, whereas theRNAreplication replaced bygenescodingfortheantigen genes encodingstructural proteins were from thegenomeofanalphavirus; The self-amplifyingRNAwasderived not limitedbyanti-vectorimmunity. vector surfaceproteins andare therefore injection. Importantly, LNPsdonotcarry gene deliveryafterintramuscular degradation andallowedforefficient shown toprotect itfrom enzymatic Encapsulation ofRNAinLNPswas nanoparticletechnology.and recent advancesinRNAsynthesis immunity andsafetyconcerns. but are hampered byanti-vector Using abioluminescentreporter The authorstookadvantageof © 2012 Macmillan Publishers Limited. Allrights reserved
responses. cellular immune humoral and induction ofboth vaccines for the potent, versatile development of for therapid generic platform a potentially could provide This approach RESEARCH HIGHLIGHTS humoral andcellularimmuneresponses. vaccines fortheinductionof both rapid developmentofpotent,versatile the a potentiallygenericplatformfor Therefore, thisapproach couldprovide subunit proteins andviral vectors. of liveviral vaccines,recombinant issues associatedwithcellculture avoiding safetyandmanufacturing cost-effective production while a cell-free manner, allowinglarge-scale, LNP–RNA vaccineisproduced vaccine potentlyinducedneutralizing (RSV) infection.TheLNP–RNA virus in amodelofrespiratory syncytial Proof ofconceptwasdemonstrated subsequent RSVinfection. pDNA and provided protection against delivery ofRNAorelectroporation of to orexceedingthoseelicitedbyVRP mice. Theseresponses were comparable producing CD4 as antigen-specificinterferon- antibodies incottonrats, aswell 14604–14609 (2012) vaccines. Nonviral deliveryofself-amplifyingRNA ORIGINAL RESEARCHPAPER The authorspointoutthatthe
Proc. NatlAcad.Sci.USA VOLUME 11 + andCD8 Alexandra Flemming
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OCTOBER 2012 Geall,A.J. + T cells in
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