Self-amplifying RNA vaccines for infectious diseases

Gene Therapy - Tập 28 Số 3-4 - Trang 117-129 - 2021
Kristie Bloom1, Fiona T. van den Berg1, Patrick Arbuthnot1
1Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa

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Plotkin SA. Vaccines: past, present and future. Nat Med. 2005;11:S5–11.

Orenstein WA, Ahmed R. Simply put: vaccination saves lives. Proc Natl Acad Sci USA. 2017;114:4031–3.

Restifo NP, Ying H, Hwang L, Leitner WW. The promise of nucleic acid vaccines. Gene Ther. 2000;7:89–92.

Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat Rev Genet. 2008;9:776–88.

Hobernik D, Bros M. DNA vaccines-how far from clinical use? Int J Mol Sci. 2018;19:3605.

Wang F, Zuroske T, Watts JK. RNA therapeutics on the rise. Nat Rev Drug Discov. 2020;19:441–2.

Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261–79.

Lundstrom K. Self-replicating RNA viruses for RNA therapeutics. Molecules. 2018;23:3310.

Tews BA, Meyers G. Self-replicating RNA. Methods Mol Biol. 2017;1499:15–35.

Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dotsch C, et al. Rescue of measles viruses from cloned DNA. Embo J. 1995;14:5773–84.

Shirley JL, de Jong YP, Terhorst C, Herzog RW. Immune responses to viral gene therapy vectors. Mol Ther. 2020;28:709–22.

Vogel AB, Lambert L, Kinnear E, Busse D, Erbar S, Reuter KC, et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol Ther. 2018;26:446–55.

Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines. 2020;5:11. https://doi.org/10.1038/s41541-020-0159-8.

Hekele A, Bertholet S, Archer J, Gibson DG, Palladino G, Brito LA, et al. Rapidly produced SAM(®) vaccine against H7N9 influenza is immunogenic in mice. Emerg Microbes Infect. 2013;2:e52.

Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2024671.

Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS-CoV-2—preliminary report. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2022483.

Beckert B, Masquida B. Synthesis of RNA by in vitro transcription. Methods Mol Biol. 2011;703:29–41.

Pardi N, Muramatsu H, Weissman D, Kariko K. In vitro transcription of long RNA containing modified nucleosides. Methods Mol Biol. 2013;969:29–42.

Cao GJ, Sarkar N. Identification of the gene for an Escherichia coli poly(A) polymerase. Proc Natl Acad Sci USA. 1992;89:10380–4.

Kääriäinen L, Ahola T. Functions of alphavirus nonstructural proteins in RNA replication. Prog Nucleic Acid Res Mol Biol. 2002;71:187–222.

Wadhwa A, Aljabbari A, Lokras A, Foged C, Thakur A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics. 2020;12:102.

Kariko K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008;16:1833–40.

Andries O, Mc Cafferty S, De Smedt SC, Weiss R, Sanders NN, Kitada TN. N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J Control Release. 2015;217:337–44.

Kauffman KJ, Mir FF, Jhunjhunwala S, Kaczmarek JC, Hurtado JE, Yang JH, et al. Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo. Biomaterials. 2016;109:78–87.

Thess A, Grund S, Mui BL, Hope MJ, Baumhof P, Fotin-Mleczek M, et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol Ther. 2015;23:1456–64.

Maruggi G, Zhang C, Li J, Ulmer JB, Yu D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol Ther. 2019;27:757–72.

Hyde JL, Chen R, Trobaugh DW, Diamond MS, Weaver SC, Klimstra WB, et al. The 5′ and 3′ ends of alphavirus RNAs—non-coding is not non-functional. Virus Res. 2015;206:99–107.

Toribio R, Diaz-Lopez I, Boskovic J, Ventoso I. An RNA trapping mechanism in Alphavirus mRNA promotes ribosome stalling and translation initiation. Nucleic Acids Res. 2016;44:4368–80.

Frolov I, Schlesinger S. Translation of Sindbis virus mRNA: analysis of sequences downstream of the initiating AUG codon that enhance translation. J Virol. 1996;70:1182–90.

Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, et al. A viral RNA structural element alters host recognition of nonself RNA. Science. 2014;343:783–7.

Reynaud JM, Kim DY, Atasheva S, Rasalouskaya A, White JP, Diamond MS, et al. IFIT1 differentially interferes with translation and replication of alphavirus genomes and promotes induction of type I interferon. PLoS Pathog. 2015;11:e1004863.

Trobaugh DW, Gardner CL, Sun C, Haddow AD, Wang E, Chapnik E, et al. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature. 2014;506:245–8.

Li Y, Teague B, Zhang Y, Su Z, Porter E, Dobosh B, et al. In vitro evolution of enhanced RNA replicons for immunotherapy. Sci Rep. 2019;9:6932.

Jemielity J, Fowler T, Zuberek J, Stepinski J, Lewdorowicz M, Niedzwiecka A, et al. Novel “anti-reverse” cap analogs with superior translational properties. Rna. 2003;9:1108–22.

Kuhn AN, Diken M, Kreiter S, Selmi A, Kowalska J, Jemielity J, et al. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther. 2010;17:961–71.

Ensinger MJ, Martin SA, Paoletti E, Moss B. Modification of the 5′-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus. Proc Natl Acad Sci USA. 1975;72:2525–9.

Shuman S. Catalytic activity of vaccinia mRNA capping enzyme subunits coexpressed in Escherichia coli. J Biol Chem. 1990;265:11960–6.

Daffis S, Szretter KJ, Schriewer J, Li J, Youn S, Errett J, et al. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 2010;468:452–6.

Vaidyanathan S, Azizian KT, Haque A, Henderson JM, Hendel A, Shore S, et al. Uridine depletion and chemical modification increase Cas9 mRNA activity and reduce immunogenicity without HPLC purification. Mol Ther Nucleic Acids. 2018;12:530–42.

Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, et al. Reversible methylation of m(6)Am in the 5′ cap controls mRNA stability. Nature. 2017;541:371–5.

McCaffrey AP. RNA epitranscriptome: role of the 5′ Cap. Genet Eng Biotechnol News. 2019;39:59–61.

Wu MZ, Asahara H, Tzertzinis G, Roy B. Synthesis of low immunogenicity RNA with high-temperature in vitro transcription. Rna. 2020;26:345–60.

Gholamalipour Y, Johnson WC, Martin CT. Efficient inhibition of RNA self-primed extension by addition of competing 3′-capture DNA-improved RNA synthesis by T7 RNA polymerase. Nucleic Acids Res. 2019;47:e118.

Kariko K, Muramatsu H, Ludwig J, Weissman D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 2011;39:e142.

Beissert T, Koste L, Perkovic M, Walzer KC, Erbar S, Selmi A, et al. Improvement of in vivo expression of genes delivered by self-amplifying RNA using vaccinia virus immune evasion proteins. Hum Gene Ther. 2017;28:1138–46.

Liu Y, Chin JM, Choo EL, Phua KKL. Messenger RNA translation enhancement by immune evasion proteins: a comparative study between EKB (vaccinia virus) and NS1 (influenza A virus). Sci Rep. 2019;9:11972.

Yoshioka N, Gros E, Li HR, Kumar S, Deacon DC, Maron C, et al. Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell. 2013;13:246–54.

Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017;24:133–43.

Kowalski PS, Rudra A, Miao L, Anderson DG. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol Ther. 2019;27:710–28.

Blakney AK, Zhu Y, McKay PF, Bouton CR, Yeow J, Tang J, et al. Big is beautiful: enhanced sarna delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer. ACS Nano. 2020;14:5711–27.

Saviano F, Lovato T, Russo A, Russo G, Shattock RJ, Alexander C, et al. Ornithine-derived oligomers and dendrimers for in vitro delivery of DNA and ex vivo transfection of skin cells via saRNA. J Mater Chem B. 2020;8:4940–9.

Blakney AK, Abdouni Y, Yilmaz G, Liu R, McKay PF, Bouton CR, et al. Mannosylated poly(ethylene imine) copolymers enhance saRNA uptake and expression in human skin explants. Biomacromolecules. 2020;21:2482–92.

Yang DC, Eldredge AC, Hickey JC, Muradyan H, Guan Z. Multivalent peptide-functionalized bioreducible polymers for cellular delivery of various RNAs. Biomacromolecules. 2020;21:1613–24.

Goswami R, Chatzikleanthous D, Lou G, Giusti F, Bonci A, Taccone M, et al. Mannosylation of LNP results in improved potency for self-amplifying RNA (SAM) vaccines. ACS Infect Dis. 2019;5:1546–58.

Perche F, Clemencon R, Schulze K, Ebensen T, Guzman CA, Pichon C. Neutral lipopolyplexes for in vivo delivery of conventional and replicative RNA vaccine. Mol Ther Nucleic Acids. 2019;17:767–75.

Ferkol T, Perales JC, Mularo F, Hanson RW. Receptor-mediated gene transfer into macrophages. Proc Natl Acad Sci USA. 1996;93:101–5.

Erbacher P, Bousser MT, Raimond J, Monsigny M, Midoux P, Roche AC. Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. Hum Gene Ther. 1996;7:721–9.

Blakney AK, McKay PF, Yus BI, Aldon Y, Shattock RJ. Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther. 2019;26:363–72.

Anderluzzi G, Lou G, Gallorini S, Brazzoli M, Johnson R, O’Hagan DT, et al. Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines. Vaccines. 2020;8:212.

Spuul P, Balistreri G, Hellstrom K, Golubtsov AV, Jokitalo E, Ahola T. Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells. J Virol. 2011;85:4739–51.

Blakney AK, McKay PF, Shattock RJ. Structural components for amplification of positive and negative strand VEEV splitzicons. Front Mol Biosci. 2018;5:71.

Beissert T, Perkovic M, Vogel A, Erbar S, Walzer KC, Hempel T, et al. A trans-amplifying RNA Vaccine strategy for induction of potent protective immunity. Mol Ther. 2020;28:119–28.

Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19:1597–608.

Carpentier KS, Morrison TE. Innate immune control of alphavirus infection. Curr Opin Virol. 2018;28:53–60.

Rauch S, Lutz J, Kowalczyk A, Schlake T, Heidenreich R. RNActive® technology: generation and testing of stable and immunogenic mRNA vaccines. Methods Mol Biol. 2017;1499:89–107.

Kallen KJ, Heidenreich R, Schnee M, Petsch B, Schlake T, Thess A, et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive(®) vaccines. Hum Vaccines Immunother. 2013;9:2263–76.

Heidenreich R, Jasny E, Kowalczyk A, Lutz J, Probst J, Baumhof P, et al. A novel RNA-based adjuvant combines strong immunostimulatory capacities with a favorable safety profile. Int J Cancer. 2015;137:372–84.

Brito LA, Chan M, Shaw CA, Hekele A, Carsillo T, Schaefer M, et al. A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol Ther. 2014;22:2118–29.

Allison AG, Gregoriadis G. Liposomes as immunological adjuvants. Nature. 1974;252:252.

Perrie Y, Crofts F, Devitt A, Griffiths HR, Kastner E, Nadella V. Designing liposomal adjuvants for the next generation of vaccines. Adv Drug Deliv Rev. 2016;99:85–96.

McCullough KC, Bassi I, Milona P, Suter R, Thomann-Harwood L, Englezou P, et al. Self-replicating replicon-RNA delivery to dendritic cells by chitosan-nanoparticles for translation in vitro and in vivo. Mol Ther Nucleic Acids. 2014;3:e173.

Manara C, Brazzoli M, Piccioli D, Taccone M, D’Oro U, Maione D, et al. Co-administration of GM-CSF expressing RNA is a powerful tool to enhance potency of SAM-based vaccines. Vaccine. 2019;37:4204–13.

Blakney AK, McKay PF, Christensen D, Yus BI, Aldon Y, Follmann F, et al. Effects of cationic adjuvant formulation particle type, fluidity and immunomodulators on delivery and immunogenicity of saRNA. J Control Release. 2019;304:65–74.

Miao L, Li L, Huang Y, Delcassian D, Chahal J, Han J, et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat Biotechnol. 2019;37:1174–85.

Pollard C, Rejman J, De Haes W, Verrier B, Van Gulck E, Naessens T, et al. Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. Mol Ther. 2013;21:251–9.

Pepini T, Pulichino AM, Carsillo T, Carlson AL, Sari-Sarraf F, Ramsauer K, et al. Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design. J Immunol. 2017;198:4012–24.

Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med. 2007;13:552–9.

Huysmans H, Zhong Z, De Temmerman J, Mui BL, Tam YK, Mc Cafferty S, et al. Expression kinetics and innate immune response after electroporation and LNP-mediated delivery of a self-amplifying mRNA in the skin. Mol Ther Nucleic Acids. 2019;17:867–78.

Zhou X, Berglund P, Rhodes G, Parker SE, Jondal M, Liljestrom P. Self-replicating Semliki Forest virus RNA as recombinant vaccine. Vaccine. 1994;12:1510–4.

Fleeton MN, Chen M, Berglund P, Rhodes G, Parker SE, Murphy M, et al. Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. J Infect Dis. 2001;183:1395–8.

Geall AJ, Verma A, Otten GR, Shaw CA, Hekele A, Banerjee K, et al. Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci USA. 2012;109:14604–9.

Perri S, Greer CE, Thudium K, Doe B, Legg H, Liu H, et al. An alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol. 2003;77:10394–403.

Scorza FB, Pardi N. New kids on the block: RNA-based influenza virus vaccines. Vaccines. 2018;6:20.

Paules CI, Fauci AS. Influenza vaccines: good, but we can do better. J Infect Dis. 2019;219:S1–4.

Magini D, Giovani C, Mangiavacchi S, Maccari S, Cecchi R, Ulmer JB, et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS ONE. 2016;11:e0161193.

McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat Commun. 2020;11:3523.

Scheuber A. Imperial social enterprise to accelerate low-cost COVID-19 vaccine. Imperial College London Health News. 2020. https://www.imperial.ac.uk/news/198053/imperial-social-enterprise-accelerate-lowcost-covid19/.

Samsa MM, Dupuy LC, Beard CW, Six CM, Schmaljohn CS, Mason PW, et al. Self-amplifying RNA vaccines for venezuelan equine encephalitis virus induce robust protective immunogenicity in mice. Mol Ther. 2019;27:850–65.

Zhong Z, Portela Catani JP, Mc Cafferty S, Couck L, Van Den Broeck W, Gorle N, et al. Immunogenicity and protection efficacy of a naked self-replicating mRNA-based zika virus vaccine. Vaccines. 2019;7:96.

Erasmus JH, Khandhar AP, Guderian J, Granger B, Archer J, Archer M, et al. A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Mol Ther. 2018;26:2507–22.

Chahal JS, Fang T, Woodham AW, Khan OF, Ling J, Anderson DG, et al. An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model. Sci Rep. 2017;7:252.

Stokes A, Pion J, Binazon O, Laffont B, Bigras M, Dubois G, et al. Nonclinical safety assessment of repeated administration and biodistribution of a novel rabies self-amplifying mRNA vaccine in rats. Regul Toxicol Pharmacol. 2020;113:104648.

Armbruster N, Jasny E, Petsch B. Advances in RNA vaccines for preventive indications: a case study of a vaccine against rabies. Vaccines. 2019;7:132.

Esparza J. A brief history of the global effort to develop a preventive HIV vaccine. Vaccine. 2013;31:3502–18.

Kwong PD, Mascola JR. HIV-1 vaccines based on antibody identification, b cell ontogeny, and epitope structure. Immunity. 2018;48:855–71.

Moore PL. The neutralizing antibody response to the HIV-1 Env protein. Curr HIV Res. 2018;16:21–8.

Jones LD, Moody MA, Thompson AB. Innovations in HIV-1 vaccine design. Clin Ther. 2020;42:499–514.

Sok D, Burton DR. Recent progress in broadly neutralizing antibodies to HIV. Nat Immunol. 2018;19:1179–88.

Padte NN, Yu J, Huang Y, Ho DD. Engineering multi-specific antibodies against HIV-1. Retrovirology. 2018;15:60.

Tremouillaux-Guiller J, Moustafa K, Hefferon K, Gaobotse G, Makhzoum A. Plant-made HIV vaccines and potential candidates. Curr Opin Biotechnol. 2020;61:209–16.

Gardner MR, Farzan M. Engineering antibody-like inhibitors to prevent and treat HIV-1 infection. Curr Opin HIV AIDS. 2017;12:294–301.

Korber B, Hraber P, Wagh K, Hahn BH. Polyvalent vaccine approaches to combat HIV-1 diversity. Immunol Rev. 2017;275:230–44.

Lin A, Balazs AB. Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1. Retrovirology. 2018;15:66.

Davis NL, Caley IJ, Brown KW, Betts MR, Irlbeck DM, McGrath KM, et al. Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. J Virol. 2000;74:371–8.

Johnston RE, Johnson PR, Connell MJ, Montefiori DC, West A, Collier ML, et al. Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660. Vaccine. 2005;23:4969–79.

Mossman SP, Bex F, Berglund P, Arthos J, O’Neil SP, Riley D, et al. Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine. J Virol. 1996;70:1953–60.

Perri S, Greer CE, Thudium K, Doe B, Legg H, Liu H, et al. An alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol. 2003;77:10394–403.

Pardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat Commun. 2017;8:14630.

Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215:1571–88.

Pardi N, LaBranche CC, Ferrari G, Cain DW, Tombacz I, Parks RJ, et al. Characterization of HIV-1 nucleoside-modified mRNA vaccines in rabbits and rhesus macaques. Mol Ther Nucleic Acids. 2019;15:36–47.

Allard SD, De Keersmaecker B, de Goede AL, Verschuren EJ, Koetsveld J, Reedijk ML, et al. A phase I/IIa immunotherapy trial of HIV-1-infected patients with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption. Clin Immunol. 2012;142:252–68.

Gandhi RT, Kwon DS, Macklin EA, Shopis JR, McLean AP, McBrine N, et al. Immunization of HIV-1-infected persons with autologous dendritic cells transfected with mRNA encoding HIV-1 Gag and Nef: results of a randomized, placebo-controlled clinical trial. J Acquir Immune Defic Syndr. 2016;71:246–53.

Gay CL, DeBenedette MA, Tcherepanova IY, Gamble A, Lewis WE, Cope AB, et al. Immunogenicity of AGS-004 dendritic cell therapy in patients treated during acute HIV infection. AIDS Res Hum Retrovir. 2018;34:111–22.

Jacobson JM, Routy JP, Welles S, DeBenedette M, Tcherepanova I, Angel JB, et al. Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: a randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr. 2016;72:31–8.

Routy JP, Boulassel MR, Yassine-Diab B, Nicolette C, Healey D, Jain R, et al. Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol. 2010;134:140–7.

Van Gulck E, Vlieghe E, Vekemans M, Van Tendeloo VF, Van De Velde A, Smits E, et al. mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients. AIDS. 2012;26:F1–12.

Gay CL, Kuruc JD, Falcinelli SD, Warren JA, Reifeis SA, Kirchherr JL, et al. Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection. Sci Rep. 2020;10:5134.

de Jong W, Leal L, Buyze J, Pannus P, Guardo A, Salgado M, et al. Therapeutic vaccine in chronically HIV-1-infected patients: a randomized, double-blind, placebo-controlled phase IIa trial with HTI-TriMix. Vaccines. 2019;7:209.

Leal L, Guardo AC, Moron-Lopez S, Salgado M, Mothe B, Heirman C, et al. Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection. AIDS. 2018;32:2533–45.

Melo M, Porter E, Zhang Y, Silva M, Li N, Dobosh B, et al. Immunogenicity of RNA replicons encoding HIV Env immunogens designed for self-assembly into nanoparticles. Mol Ther. 2019;27:2080–90.

Bogers WM, Oostermeijer H, Mooij P, Koopman G, Verschoor EJ, Davis D, et al. Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion. J Infect Dis. 2015;211:947–55.

Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366:1275–86.

Moyo N, Vogel AB, Buus S, Erbar S, Wee EG, Sahin U, et al. Efficient Induction of T cells against conserved HIV-1 regions by mosaic vaccines delivered as self-amplifying mRNA. Mol Ther Methods Clin Dev. 2019;12:32–46.

Kollmann TR. Variation between populations in the innate immune response to vaccine adjuvants. Front Immunol. 2013;4:81.

Brazzoli M, Magini D, Bonci A, Buccato S, Giovani C, Kratzer R, et al. Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. J Virol. 2016;90:332–44.

Lazzaro S, Giovani C, Mangiavacchi S, Magini D, Maione D, Baudner B, et al. CD8 T-cell priming upon mRNA vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes. Immunology. 2015;146:312–26.

Chahal JS, Khan OF, Cooper CL, McPartlan JS, Tsosie JK, Tilley LD, et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci USA. 2016;113:E4133–42.

Demoulins T, Ebensen T, Schulze K, Englezou PC, Pelliccia M, Guzman CA, et al. Self-replicating RNA vaccine functionality modulated by fine-tuning of polyplex delivery vehicle structure. J Control Release. 2017;266:256–71.

Englezou PC, Sapet C, Demoulins T, Milona P, Ebensen T, Schulze K, et al. Self-amplifying replicon RNA delivery to dendritic cells by cationic lipids. Mol Ther Nucleic Acids. 2018;12:118–34.

Kofler RM, Aberle JH, Aberle SW, Allison SL, Heinz FX, Mandl CW. Mimicking live flavivirus immunization with a noninfectious RNA vaccine. Proc Natl Acad Sci USA. 2004;101:1951–6.

Aberle JH, Aberle SW, Kofler RM, Mandl CW. Humoral and cellular immune response to RNA immunization with flavivirus replicons derived from tick-borne encephalitis virus. J Virol. 2005;79:15107–13.

Cu Y, Broderick KE, Banerjee K, Hickman J, Otten G, Barnett S, et al. Enhanced delivery and potency of self-amplifying mRNA vaccines by electroporation in situ. Vaccines. 2013;1:367–83.

Luo F, Zheng L, Hu Y, Liu S, Wang Y, Xiong Z, et al. Induction of protective immunity against toxoplasma gondii in mice by nucleoside triphosphate hydrolase-II (NTPase-II) self-amplifying RNA vaccine encapsulated in lipid nanoparticle (LNP). Front Microbiol. 2017;8:605.

Maruggi G, Chiarot E, Giovani C, Buccato S, Bonacci S, Frigimelica E, et al. Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens. Vaccine. 2017;35:361–8.