Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2021).
Google Scholar
Kennedy, R. B., Ovsyannikova, I. G., Palese, P. & Poland, G. A. Current challenges in vaccinology. Front. Immunol. 11, 1181 (2020).
Google Scholar
Verbeke, R., Lentacker, I., De Smedt, S. C. & Dewitte, H. Three decades of messenger RNA vaccine development. Nano Today 28, 100766 (2019).
Google Scholar
Sahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics — developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014).
Google Scholar
Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018).
Google Scholar
Kis, Z., Kontoravdi, C., Dey, A. K., Shattock, R. & Shah, N. Rapid development and deployment of high-volume vaccines for pandemic response. J. Adv. Manuf. Process. 2, e10060 (2020).
Google Scholar
Freyn, A. W. et al. A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol. Ther. 28, 1569–1584 (2020).
Google Scholar
Wu, K. et al. Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. bioRxiv https://www.biorxiv.org/content/10.1101/2021.04.13.439482v1 (2021).
Bloom, K., van den Berg, F. & Arbuthnot, P. Self-amplifying RNA vaccines for infectious diseases. Gene Ther. 28, 117–129 (2021).
Google Scholar
Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C. & Thakur, A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics 12, 102 (2020).
Google Scholar
Linares-Fernández, S., Lacroix, C., Exposito, J. Y. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol. Med. 26, 311–323 (2020).
Google Scholar
Xiong, Q., Lee, G. Y., Ding, J., Li, W. & Shi, J. Biomedical applications of mRNA nanomedicine. Nano Res. 11, 5281–5309 (2018).
Google Scholar
Mugridge, J. S., Coller, J. & Gross, J. D. Structural and molecular mechanisms for the control of eukaryotic 5′–3′ mRNA decay. Nat. Struct. Mol. Biol. 25, 1077–1085 (2018).
Google Scholar
Berkovits, B. D. & Mayr, C. Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization. Nature 522, 363–367 (2015).
Google Scholar
Weng, Y. et al. The challenge and prospect of mRNA therapeutics landscape. Biotechnol. Adv. 40, 107534 (2020).
Google Scholar
Sample, P. J. et al. Human 5′ UTR design and variant effect prediction from a massively parallel translation assay. Nat. Biotechnol. 37, 803–809 (2019). This study designs novel UTR sequences and predicts ribosome loading using deep learning.
Google Scholar
Orlandini von Niessen, A. G. et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3′ UTRs identified by cellular library screening. Mol. Ther. 27, 824–836 (2019).
Google Scholar
Zeng, C. et al. Leveraging mRNA sequences and nanoparticles to deliver SARS-CoV-2 antigens in vivo. Adv. Mater. 32, 2004452 (2020).
Google Scholar
Chen, C. Y. A. & Shyu, A. B. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci. 20, 465–470 (1995).
Google Scholar
Leppek, K., Das, R. & Barna, M. Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them. Nat. Rev. Mol. Cell Biol. 19, 158–174 (2018).
Google Scholar
von der Mülbe, F., Hoerr, I. & Pascolo, S. Pharmaceutical composition containing a stabilised mRNA optimised for translation in its coding regions. US 2015/0104476 A1 (2015).
Spencer, P. S., Siller, E., Anderson, J. F. & Barral, J. M. Silent substitutions predictably alter translation elongation rates and protein folding efficiencies. J. Mol. Biol. 422, 328–335 (2012).
Google Scholar
Hajj, K. A. & Whitehead, K. A. Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2, 17056 (2017).
Google Scholar
Vaidyanathan, S. et al. Uridine depletion and chemical modification increase Cas9 mRNA activity and reduce immunogenicity without HPLC purification. Mol. Ther. Nucleic Acids 12, 530–542 (2018).
Google Scholar
Buschmann, M. D. et al. Nanomaterial delivery systems for mRNA vaccines. Vaccines 9, 65 (2021).
Google Scholar
Thess, A. et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. 23, 1456–1464 (2015).
Google Scholar
Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020).
Google Scholar
Sahin, U. et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature 595, 572–577 (2021).
Google Scholar
Pardi, N., Hogan, M. J. & Weissman, D. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 65, 14–20 (2020).
Google Scholar
Stadler, C. R. et al. Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. Nat. Med. 23, 815–817 (2017).
Google Scholar
Eberle, F., Sahin, U., Kuhn, A., Vallazza, B. & Diken, M. Stabilization of poly(A) sequence encoding Dna sequences. US 2017/0166905 A1 (2017).
Kim, J., Eygeris, Y., Gupta, M. & Sahay, G. Self-assembled mRNA vaccines. Adv. Drug Deliv. Rev. 170, 83–112 (2021).
Google Scholar
Malone, R. W., Felgner, P. L. & Verma, I. M. Cationic liposome-mediated RNA transfection. Proc. Natl Acad. Sci. USA 86, 6077–6081 (1989). First demonstration of mRNA delivery using cationic lipids.
Google Scholar
Kauffman, K. J., Webber, M. J. & Anderson, D. G. Materials for non-viral intracellular delivery of messenger RNA therapeutics. J. Control. Rel. 240, 227–234 (2016).
Google Scholar
Cui, S. et al. Correlation of the cytotoxic effects of cationic lipids with their headgroups. Toxicol. Res. 7, 473–479 (2018).
Google Scholar
Lonez, C., Vandenbranden, M. & Ruysschaert, J. M. Cationic lipids activate intracellular signaling pathways. Adv. Drug Deliv. Rev. 64, 1749–1758 (2012).
Google Scholar
Cullis, P. R. & Hope, M. J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 25, 1467–1475 (2017).
Google Scholar
Sahay, G., Alakhova, D. Y. & Kabanov, A. V. Endocytosis of nanomedicines. J. Control. Rel. 145, 182–195 (2010).
Google Scholar
Patel, S. et al. Brief update on endocytosis of nanomedicines. Adv. Drug Deliv. Rev. 144, 90–111 (2019).
Google Scholar
Semple, S. C. et al. Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures. Biochim. Biophys. Acta 1510, 152–166 (2001).
Google Scholar
Heyes, J., Palmer, L., Bremner, K. & MacLachlan, I. Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J. Control. Rel. 107, 276–287 (2005).
Google Scholar
Jayaraman, M. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int. Ed. 51, 8529–8533 (2012). This study reports the synthesis of DLin-MC3-DMA, the ionizable lipid used in the first siRNA therapeutic patisiran.
Google Scholar
Ramaswamy, S. et al. Systemic delivery of factor IX messenger RNA for protein replacement therapy. Proc. Natl Acad. Sci. USA 114, E1941–E1950 (2017).
Google Scholar
Veiga, N. et al. Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes. Nat. Commun. 9, 4493 (2018).
Google Scholar
Zhang, M., Sun, J., Li, M. & Jin, X. Modified mRNA-LNP vaccines confer protection against experimental DENV-2 infection in mice. Mol. Ther. Methods Clin. Dev. 18, 702–712 (2020).
Google Scholar
Hajj, K. A. et al. A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivo. Nano Lett. 20, 5167–5175 (2020).
Google Scholar
Love, K. T. et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl Acad. Sci. USA 107, 1864–1869 (2010).
Google Scholar
Whitehead, K. A. et al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun. 5, 4277 (2014).
Google Scholar
Fenton, O. S. et al. Bioinspired alkenyl amino alcohol ionizable lipid materials for highly potent in vivo mRNA delivery. Adv. Mater. 28, 2939–2943 (2016).
Google Scholar
Li, B. et al. An orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo. Nano Lett. 15, 8099–8107 (2015).
Google Scholar
Wei, T., Cheng, Q., Min, Y. L., Olson, E. N. & Siegwart, D. J. Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing. Nat. Commun. 11, 3232 (2020).
Google Scholar
Zhou, K. et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. Proc. Natl Acad. Sci. USA 113, 520–525 (2016).
Google Scholar
Sabnis, S. et al. A novel amino lipid series for mRNA delivery: improved endosomal escape and sustained pharmacology and safety in non-human primates. Mol. Ther. 26, 1509–1519 (2018). This study reports the synthesis of SM-102 (Lipid 8); the ionizable lipid used in Moderna’s SARS-CoV-2 vaccine candidate mRNA-1273.
Google Scholar
Hope, M. et al. Lipid nanoparticle formulations. WO 2018/081480 A1 (2018).
Hajj, K. A. et al. Branched-tail lipid nanoparticles potently deliver mRNA in vivo due to enhanced ionization at endosomal pH. Small 15, 1805097 (2019).
Google Scholar
Alabi, C. A. et al. Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery. Proc. Natl Acad. Sci. USA 110, 12881–12886 (2013).
Google Scholar
Miao, L. et al. Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver. Nat. Commun. 11, 2424 (2020). This study reports the synthesis of a new lipid library that delivers mRNA using the albumin receptor.
Google Scholar
Lokugamage, M. P., Sago, C. D., Gan, Z., Krupczak, B. R. & Dahlman, J. E. Constrained nanoparticles deliver siRNA and sgRNA to T cells in vivo without targeting ligands. Adv. Mater. 31, 1902251 (2019).
Google Scholar
Zhao, X. et al. Imidazole-based synthetic lipidoids for in vivo mRNA delivery into primary T lymphocytes. Angew. Chem. Int. Ed. Engl. 132, 20258–20264 (2020).
Google Scholar
Miao, L. et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019). This study reports the synthesis of a lipid library that activates immune cells through STING rather than TLRs.
Google Scholar
Hou, X. et al. Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat. Nanotechnol. 15, 41–46 (2020).
Google Scholar
Yang, S. T., Kreutzberger, A. J. B., Lee, J., Kiessling, V. & Tamm, L. K. The role of cholesterol in membrane fusion. Chem. Phys. Lipids 199, 136–143 (2016).
Google Scholar
Paunovska, K. et al. Nanoparticles containing oxidized cholesterol deliver mRNA to the liver microenvironment at clinically relevant doses. Adv. Mater. 31, 1807748 (2019).
Google Scholar
Patel, S. et al. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nat. Commun. 11, 983 (2020).
Google Scholar
Kim, J., Mukherjee, A., Nelson, D., Jozic, A. & Sahay, G. Rapid generation of circulating and mucosal decoy ACE2 using mRNA nanotherapeutics for the potential treatment of SARS-CoV-2. bioRxiv https://www.biorxiv.org/content/10.1101/2020.07.24.205583v1 (2020).
Sahay, G. et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31, 653–658 (2013).
Google Scholar
Cheng, X. & Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 99, 129–137 (2016).
Google Scholar
Koltover, I., Salditt, T., Rädler, J. O. & Safinya, C. R. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281, 78–81 (1998).
Google Scholar
Kauffman, K. J. et al. Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs. Nano Lett. 15, 7300–7306 (2015).
Google Scholar
Ball, R. L., Hajj, K. A., Vizelman, J., Bajaj, P. & Whitehead, K. A. Lipid nanoparticle formulations for enhanced co-delivery of siRNA and mRNA. Nano Lett. 18, 3814–3822 (2018).
Google Scholar
Lee, S. M. et al. A systematic study of unsaturation in lipid nanoparticles leads to improved mRNA transfection in vivo. Angew. Chem. Int. Ed. 60, 5848–5853 (2021).
Google Scholar
Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing. Nat. Mater. 20, 701–710 (2021).
Google Scholar
Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020). This study demonstrates that helper lipid charge regulates organ delivery specificity.
Google Scholar
Kulkarni, J. A. et al. On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA. ACS Nano 12, 4787–4795 (2018).
Google Scholar
Kanasty, R., Dorkin, J. R., Vegas, A. & Anderson, D. Delivery materials for siRNA therapeutics. Nat. Mater. 12, 967–977 (2013).
Google Scholar
Oberli, M. A. et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 17, 1326–1335 (2017).
Google Scholar
Zhu, X. et al. Surface de-PEGylation controls nanoparticle-mediated siRNA delivery in vitro and in vivo. Theranostics 7, 1990–2002 (2017).
Google Scholar
Akinc, A. et al. Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol. Ther. 17, 872–879 (2009).
Google Scholar
Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol. Ther. 27, 710–728 (2019).
Google Scholar
Bus, T., Traeger, A. & Schubert, U. S. The great escape: how cationic polyplexes overcome the endosomal barrier. J. Mater. Chem. B 6, 6904–6918 (2018).
Google Scholar
Moghimi, S. M. et al. A two-stage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy. Mol. Ther. 11, 990–995 (2005).
Google Scholar
Ulkoski, D., Bak, A., Wilson, J. T. & Krishnamurthy, V. R. Recent advances in polymeric materials for the delivery of RNA therapeutics. Expert Opin. Drug. Deliv. 16, 1149–1167 (2019).
Google Scholar
Ke, X. et al. Surface-functionalized PEGylated nanoparticles deliver messenger RNA to pulmonary immune cells. ACS Appl. Mater. Interfaces 12, 35835–35844 (2020).
Google Scholar
Li, M. et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways. J. Control. Rel. 228, 9–19 (2016).
Google Scholar
Li, M. et al. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses. Acta Biomater. 64, 237–248 (2017).
Google Scholar
Tan, L. et al. Optimization of an mRNA vaccine assisted with cyclodextrin-polyethyleneimine conjugates. Drug Deliv. Transl. Res. 10, 678–689 (2020).
Google Scholar
Breunig, M., Lungwitz, U., Liebl, R. & Goepferich, A. Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc. Natl Acad. Sci. USA 104, 14454–14459 (2007).
Google Scholar
Kaczmarek, J. C. et al. Optimization of a degradable polymer-lipid nanoparticle for potent systemic delivery of mRNA to the lung endothelium and immune cells. Nano Lett. 18, 6449–6454 (2018).
Google Scholar
Kaczmarek, J. C. et al. Polymer–lipid nanoparticles for systemic delivery of mRNA to the lungs. Angew. Chem. — Int. Ed. 55, 13808–13812 (2016).
Google Scholar
Patel, A. K. et al. Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium. Adv. Mater. 31, 1805116 (2019).
Google Scholar
Lynn, D. M. & Langer, R. Degradable poly(β-amino esters): synthesis, characterization, and self-assembly with plasmid DNA. J. Am. Chem. Soc. 122, 10761–10768 (2000).
Google Scholar
Mintzer, M. A. & Simanek, E. E. Nonviral vectors for gene delivery. Chem. Rev. 109, 259–302 (2009).
Google Scholar
Kim, H. J. et al. Fine-tuning of hydrophobicity in amphiphilic polyaspartamide derivatives for rapid and transient expression of messenger RNA directed toward genome engineering in brain. ACS Cent. Sci. 5, 1866–1875 (2019).
Google Scholar
Matsui, A., Uchida, S., Ishii, T., Itaka, K. & Kataoka, K. Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases. Sci. Rep. 5, 15810 (2015).
Google Scholar
Lin, C. Y. et al. Messenger RNA-based therapeutics for brain diseases: an animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles. J. Control. Rel. 235, 268–275 (2016).
Google Scholar
Crowley, S. T., Fukushima, Y., Uchida, S., Kataoka, K. & Itaka, K. Enhancement of motor function recovery after spinal cord injury in mice by delivery of brain-derived neurotrophic factor mRNA. Mol. Ther. Nucleic Acids 17, 465–476 (2019).
Google Scholar
Aini, H. et al. Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Sci. Rep. 6, 18743 (2016).
Google Scholar
Baba, M., Itaka, K., Kondo, K., Yamasoba, T. & Kataoka, K. Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles. J. Control. Rel. 201, 41–48 (2015).
Google Scholar
McKinlay, C. J. et al. Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals. Proc. Natl Acad. Sci. USA 114, E448–E456 (2017).
Google Scholar
Haabeth, O. A. W. et al. mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice. Proc. Natl Acad. Sci. USA 115, E9153–E9161 (2018).
Google Scholar
Mccarthy, H. O. et al. Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery. J. Control. Rel. 189, 141–149 (2014).
Google Scholar
Li, W., Nicol, F. & Szoka, F. C. GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv. Drug Deliv. Rev. 56, 967–985 (2004).
Google Scholar
Udhayakumar, V. K. et al. Arginine-rich peptide-based mRNA nanocomplexes efficiently instigate cytotoxic T cell immunity dependent on the amphipathic organization of the peptide. Adv. Healthc. Mater. 6, 1601412 (2017).
Google Scholar
van den Brand, D. et al. Peptide-mediated delivery of therapeutic mRNA in ovarian cancer. Eur. J. Pharm. Biopharm. 141, 180–190 (2019).
Google Scholar
Kallen, K. J. et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive® vaccines. Hum. Vaccines Immunother. 9, 2263–2276 (2013).
Google Scholar
Weide, B. et al. Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J. Immunother. 32, 498–507 (2009).
Google Scholar
Kübler, H. et al. Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study. J. Immunother. Cancer 3, 26 (2015).
Google Scholar
Papachristofilou, A. et al. Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. J. Immunother. Cancer 7, 38–38 (2019).
Google Scholar
Brito, L. A. et al. A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol. Ther. 22, 2118–2129 (2014).
Google Scholar
Tsai, T. F. Fluad®-MF59®-adjuvanted influenza vaccine in older adults. Infect. Chemother. 45, 159–174 (2013).
Google Scholar
O’Hagan, D. T., Ott, G. S., De Gregorio, E. & Seubert, A. The mechanism of action of MF59 – an innately attractive adjuvant formulation. Vaccine 30, 4341–4348 (2012).
Google Scholar
Mosca, F. et al. Molecular and cellular signatures of human vaccine adjuvants. Proc. Natl Acad. Sci. USA 105, 10501–10506 (2008).
Google Scholar
Seubert, A., Monaci, E., Pizza, M., O’Hagan, D. T. & Wack, A. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J. Immunol. 180, 5402–5412 (2008).
Google Scholar
Gómez-Aguado, I. et al. Nanomedicines to deliver mRNA: state of the art and future perspectives. Nanomaterials 10, 364 (2020).
Google Scholar
Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). The first report of the discovery of SARS-CoV-2.
Google Scholar
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A. & Ng, L. F. P. The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 20, 363–374 (2020).
Google Scholar
Alon, R. et al. Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19. Nat. Rev. Immunol. 21, 49–64 (2021).
Google Scholar
Shang, J. et al. Cell entry mechanisms of SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 11727–11734 (2020). This study describes the cell-entry mechanism of SARS-CoV-2.
Google Scholar
Knezevic, I., Liu, M. A., Peden, K., Zhou, T. & Kang, H.-N. Development of mRNA vaccines: scientific and regulatory issues. Vaccines 9, 81 (2021).
Google Scholar
Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260–1263 (2020).
Google Scholar
Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell 181, 281–292.e6 (2020).
Google Scholar
Vogel, A. B. et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature 592, 283–289 (2021).
Google Scholar
Mulligan, M. J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586, 589–593 (2020).
Google Scholar
Walsh, E. E. et al. Safety and immunogenicity of two RNA-based covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020).
Google Scholar
Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
Google Scholar
Dagan, N. et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N. Engl. J. Med. 384, 1412–1423 (2021).
Google Scholar
Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586, 567–571 (2020). This study reports the development process of mRNA-1273.
Google Scholar
Corbett, K. S. et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 383, 1544–1555 (2020).
Google Scholar
Corbett, K. S. et al. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science eabj0299 (2021).
Jackson, L. A. et al. An mRNA vaccine against SARS-CoV-2 — preliminary report. N. Engl. J. Med. 383, 1920–1931 (2020).
Google Scholar
Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2020).
Google Scholar
Thompson, M. G. et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — eight U.S. locations, December 2020–March 2021. Morb. Mortal. Wkly Rep. 70, 495–500 (2021).
Google Scholar
Kremsner, P. et al. Phase 1 assessment of the safety and immunogenicity of an mRNA- lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. medRxiv https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1 (2020).
Roth, N. et al. CV2CoV, an enhanced mRNA-based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats. bioRxiv, https://www.biorxiv.org/content/10.1101/2021.05.13.443734v1.full (2021).
Zhang, N. N. et al. A thermostable mRNA vaccine against COVID-19. Cell 182, 1271–1283.e16 (2020).
Google Scholar
McKay, P. F. et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat. Commun. 11, 3–9 (2020).
Google Scholar
de Alwis, R. et al. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol. Ther. 29, 1970–1983 (2021).
Google Scholar
Iuliano, A. et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 391, 1285–1300 (2018).
Google Scholar
Zost, S. J. et al. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc. Natl Acad. Sci. USA 114, 12578–12583 (2017).
Google Scholar
Hekele, A. et al. Rapidly produced SAM® vaccine against H7N9 influenza is immunogenic in mice. Emerg. Microbes Infect. 2, e52 (2013).
Google Scholar
Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012).
Google Scholar
Brazzoli, M. et al. Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. J. Virol. 90, 332–344 (2016).
Google Scholar
Magini, D. et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS ONE 11, e0161193 (2016).
Google Scholar
Vogel, A. B. et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol. Ther. 26, 446–455 (2018).
Google Scholar
Goswami, R. et al. Mannosylation of LNP results in improved potency for self-amplifying RNA (SAM) vaccines. ACS Infect. Dis. 5, 1546–1558 (2019).
Google Scholar
Zhuang, X. et al. mRNA vaccines encoding the HA protein of influenza A H1N1 virus delivered by cationic lipid nanoparticles induce protective immune responses in mice. Vaccines 8, 123 (2020).
Google Scholar
Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mrna vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 25, 1316–1327 (2017).
Google Scholar
Nachbagauer, R. et al. A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies. NPJ Vaccines 2, 26 (2017).
Google Scholar
Pardi, N. et al. Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nat. Commun. 9, 3361 (2018).
Google Scholar
Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019).
Google Scholar
Poland, G. A. et al. Development of vaccines against Zika virus. Lancet Infect. Dis. 18, e211–e219 (2018).
Google Scholar
Dowd, K. A. et al. Broadly neutralizing activity of zika virus-immune sera identifies a single viral serotype. Cell Rep. 16, 1485–1491 (2016).
Google Scholar
Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543, 248–251 (2017).
Google Scholar
Wollner, C. J. & Richner, J. M. mRNA vaccines against flaviviruses. Vaccines 9, 1–13 (2021).
Google Scholar
Dejnirattisai, W. et al. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with Zika virus. Nat. Immunol. 17, 1102–1108 (2016).
Google Scholar
Richner, J. M. et al. Modified mRNA vaccines protect against Zika virus infection. Cell 168, 1114–1125.e10 (2017).
Google Scholar
Erasmus, J. H. et al. Intramuscular delivery of replicon RNA encoding ZIKV-117 human monoclonal antibody protects against Zika virus. Infect. Mol. Ther. Methods Clin. Dev. 18, 402–414 (2020).
Google Scholar
Kose, N. et al. A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against Chikungunya infection. Sci. Immunol. 4, 6647 (2019).
Google Scholar
Dybul, M. et al. The case for an HIV cure and how to get there. Lancet HIV 8, e51–e58 (2021).
Google Scholar
Mascola, J. R. The modern era of HIV-1 vaccine development. Science 349, 139–140 (2015).
Google Scholar
Bogers, W. M. 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. 211, 947–955 (2015).
Google Scholar
Pollard, C. et al. Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. Mol. Ther. 21, 251–259 (2013).
Google Scholar
Moyo, N. 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. 12, 32–46 (2019).
Google Scholar
Zhao, M., Li, M., Zhang, Z., Gong, T. & Sun, X. Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA. Drug Deliv. 23, 2596–2607 (2016).
Google Scholar
Blakney, A. K., McKay, P. F., Yus, B. I., Aldon, Y. & Shattock, R. J. Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther. 26, 363–372 (2019).
Google Scholar
Pardi, N. et al. Characterization of HIV-1 nucleoside-modified mRNA vaccines in rabbits and rhesus macaques. Mol. Ther. Nucleic Acids 15, 36–47 (2019).
Google Scholar
Singh, A. Eliciting B cell immunity against infectious diseases using nanovaccines. Nat. Nanotechnol. 16, 16–24 (2021).
Google Scholar
Corey, L. et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N. Engl. J. Med. 384, 1003–1014 (2021).
Google Scholar
Pardi, N. et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat. Commun. 8, 6–13 (2017).
Google Scholar
Shi, T. et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390, 946–958 (2017).
Google Scholar
Falsey, A. R., Hennessey, P. A., Formica, M. A., Cox, C. & Walsh, E. E. Respiratory syncytial virus infection in elderly and high-risk adults. N. Engl. J. Med. 352, 1749–1759 (2005).
Google Scholar
Kim, H. W. et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am. J. Epidemiol. 89, 422–434 (1969).
Google Scholar
Haynes, B. F. et al. Prospects for a safe COVID-19 vaccine. Sci. Transl. Med. 12, 1–13 (2020).
Google Scholar
Mazur, N. I. et al. The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect. Dis. 18, e295–e311 (2018).
Google Scholar
Crank, M. C. et al. A proof of concept for structure-based vaccine design targeting RSV in humans. Science 365, 505–509 (2019).
Google Scholar
McLellan, J. S. et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340, 1113–1117 (2013).
Google Scholar
McLellan, J. S. et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 342, 592–598 (2013).
Google Scholar
Krarup, A. et al. A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat. Commun. 6, 1–12 (2015).
Google Scholar
Espeseth, A. S. et al. Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protective in rodent models of RSV infection. NPJ Vaccines 5, 1–14 (2020).
Google Scholar
Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109, 14604–14609 (2012).
Google Scholar
Aliprantis, A. O. et al. A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. Hum. Vaccines Immunother. 17, 1248–1261 (2021).
Google Scholar
Kaner, J. & Schaack, S. Understanding Ebola: the 2014 epidemic. Glob. Heal. 12, 53 (2016).
Google Scholar
Agnandji, S. T. et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe. N. Engl. J. Med. 374, 1647–1660 (2016).
Google Scholar
Chahal, J. S. 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 113, E5250 (2016).
Google Scholar
Meyer, M. et al. Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 217, 451–455 (2018).
Google Scholar
Hampson, K. et al. Estimating the global burden of endemic canine rabies. PLoS Negl. Trop. Dis. 9, e0003709 (2015).
Google Scholar
Schnee, M. et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl. Trop. Dis. 10, e0004746 (2016).
Google Scholar
Alberer, M. et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet 390, 1511–1520 (2017).
Google Scholar
Lutz, J. et al. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines 2, 29 (2017).
Google Scholar
Aldrich, C. et al. Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: a phase 1 trial. Vaccine 39, 1310–1318 (2021).
Google Scholar
Sun, T. et al. A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria. Proc. Natl Acad. Sci. USA 109, E2117 (2012).
Google Scholar
Baeza Garcia, A. et al. Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Nat. Commun. 9, 2714 (2018).
Google Scholar
Raj, D. K. et al. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature 582, 104–108 (2020).
Google Scholar
Kedmi, R. et al. A modular platform for targeted RNAi therapeutics. Nat. Nanotechnol. 13, 214–219 (2018).
Google Scholar
Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396–401 (2016).
Google Scholar
Irvine, D. J., Aung, A. & Silva, M. Controlling timing and location in vaccines. Adv. Drug Deliv. Rev. 158, 91–115 (2020).
Google Scholar
Cirelli, K. M. & Crotty, S. Germinal center enhancement by extended antigen availability. Curr. Opin. Immunol. 47, 64–69 (2017).
Google Scholar
Hu, J. K. et al. Murine antibody responses to cleaved soluble HIV-1 envelope trimers are highly restricted in specificity. J. Virol. 89, 10383–10398 (2015).
Google Scholar
Tam, H. H. et al. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. Proc. Natl Acad. Sci. USA 113, E6639–E6648 (2016).
Google Scholar
Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018).
Google Scholar
Laczkó, D. et al. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity 53, 724–732.e7 (2020).
Google Scholar
Lederer, K. et al. SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. Immunity 53, 1281–1295.e5 (2020).
Google Scholar
Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce robust plasmablast and germinal centre responses in humans. Nature https://doi.org/10.1038/s41586-021-03738-2 (2021).
Google Scholar
Turner, J. S. et al. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 586, 127–132 (2020).
Google Scholar
Doria-Rose, N. et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for covid-19. N. Engl. J. Med. 384, 2259–2261 (2021).
Google Scholar
Li, Y. et al. Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. J. Virol. 85, 8954–8967 (2011).
Google Scholar
Yuan, M. et al. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants. Science https://doi.org/10.1101/2021.02.16.430500 (2021).
Google Scholar
Wang, Z. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616–622 (2021).
Google Scholar
Liu, Y. et al. Neutralizing activity of BNT162b2-elicited serum. N. Engl. J. Med. 384, 1466–1468 (2021).
Google Scholar
Wu, K. et al. Serum neutralizing activity elicited by mRNA-1273 vaccine. N. Engl. J. Med. 384, 1468–1470 (2021).
Google Scholar
Pegu, A. et al. Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants. Science 12, eabj4176 (2021).
Google Scholar
Saunders, K. O. et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature 594, 553–559 (2021). This study suggests that mRNA vaccines can be used as a platform to develop pancoronavirus vaccines.
Google Scholar
Shimabukuro, T. T., Cole, M. & Su, J. R. Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US — December 14, 2020-January 18, 2021. JAMA 325, 1101–1102 (2021).
Google Scholar
McNeil, M. M. et al. Risk of anaphylaxis after vaccination in children and adults. J. Allergy Clin. Immunol. 137, 868–878 (2016).
Google Scholar
Vrieze, J. Suspicions grow that nanoparticles in Pfizer’s COVID-19 vaccine trigger rare allergic reactions. Science https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions (2020).
Besin, G. et al. Accelerated blood clearance of lipid nanoparticles entails a biphasic humoral response of B-1 followed by B-2 lymphocytes to distinct antigenic moieties. ImmunoHorizons 3, 282–293 (2019). This study describes the potential mechanism of anti-PEG-mediated accelerated blood clearance of LNPs.
Google Scholar
Abu Lila, A. S., Kiwada, H. & Ishida, T. The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. J. Control. Rel. 172, 38–47 (2013).
Google Scholar
Kozma, G. T., Shimizu, T., Ishida, T. & Szebeni, J. Anti-PEG antibodies: properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals. Adv. Drug Deliv. Rev. 154–155, 163–175 (2020).
Google Scholar
Vermillion, M. S. & Klein, S. L. Pregnancy and infection: using disease pathogenesis to inform vaccine strategy. NPJ Vaccines 3, 6 (2018).
Google Scholar
Bialas, K. M., Swamy, G. K. & Permar, S. R. Perinatal cytomegalovirus and varicella zoster virus infections: epidemiology, prevention, and treatment. Clin. Perinatol. 42, 61–75 (2015).
Google Scholar
Yockey, L. J., Lucas, C. & Iwasaki, A. Contributions of maternal and fetal antiviral immunity in congenital disease. Science 368, 608–612 (2020).
Google Scholar
Barrero-Castillero, A. et al. COVID-19: neonatal-perinatal perspectives. J. Perinatol. 41, 940–951 (2021).
Google Scholar
Fenizia, C. et al. Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nat. Commun. 11, 5128 (2020).
Google Scholar
Roopenian, D. C. & Akilesh, S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7, 715–725 (2007).
Google Scholar
Richner, J. M. et al. Vaccine mediated protection against Zika virus-induced congenital disease. Cell 170, 273–283.e12 (2017).
Google Scholar
Jagger, B. W. et al. Protective efficacy of nucleic acid vaccines against transmission of Zika virus during pregnancy in mice. J. Infect. Dis. 220, 1577–1588 (2019).
Google Scholar
LaTourette, P. C. et al. Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine. Vaccine 38, 7409–7413 (2020).
Google Scholar
Maruggi, G. et al. Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens. Vaccine 35, 361–368 (2017).
Google Scholar
Willis, E. et al. Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice. Sci. Transl. Med. 12, eaav5701 (2020).
Google Scholar
Collier, A. Y. et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA 325, 2370–2380 (2021).
Google Scholar
Shimabukuro, T. T. et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N. Engl. J. Med. 384, 2273–2282 (2021).
Google Scholar
Crooke, S. N., Ovsyannikova, I. G., Poland, G. A. & Kennedy, R. B. Immunosenescence and human vaccine immune responses. Immun. Ageing 16, 25 (2019).
Google Scholar
Yanez, N. D., Weiss, N. S., Romand, J. A. & Treggiari, M. M. COVID-19 mortality risk for older men and women. BMC Public Health 20, 1742 (2020).
Google Scholar
Van Den Biggelaar, A. H. J. et al. Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study. Exp. Gerontol. 39, 1407–1414 (2004).
Google Scholar
Palmer, D. B. The effect of age on thymic function. Front. Immunol. 4, 316 (2013).
Google Scholar
Lazuardi, L. et al. Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology 114, 37–43 (2005).
Google Scholar
Qi, Q. et al. Diversity and clonal selection in the human T-cell repertoire. Proc. Natl Acad. Sci. USA 111, 13139–13144 (2014).
Google Scholar
Fang, F. et al. Expression of CD39 on activated T cells impairs their survival in older individuals. Cell Rep. 14, 1218–1231 (2016).
Google Scholar
Boucher, N. et al. CD28 expression in T cell aging and human longevity. Exp. Gerontol. 33, 267–282 (1998).
Google Scholar
Yang, J. et al. Effectiveness, immunogenicity, and safety of influenza vaccines with MF59 adjuvant in healthy people of different age groups. Medicine 99, e19095 (2020).
Google Scholar
Ansaldi, F. et al. Cross-protection by MF59TM-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. Vaccine 26, 1525–1529 (2008).
Google Scholar
Kaiser, J. Temperature concerns could slow the rollout of new coronavirus vaccines. Science https://www.sciencemag.org/news/2020/11/temperature-concerns-could-slow-rollout-new-coronavirus-vaccines (2020).
Stitz, L. et al. A thermostable messenger RNA based vaccine against rabies. PLoS Negl. Trop. Dis. 11, e0006108 (2017).
Google Scholar
Lazarus, J. V. et al. A global survey of potential acceptance of a COVID-19 vaccine. Nat. Med. 27, 225–228 (2020).
Google Scholar
Sallam, M. Covid-19 vaccine hesitancy worldwide: a concise systematic review of vaccine acceptance rates. Vaccines 9, 1–15 (2021).
Lippi, G. & Henry, B. M. How will emerging SARS-CoV-2 variants impact herd immunity? Ann. Transl. Med. 9, 585–585 (2021).
Google Scholar
Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).
Google Scholar
Goldberg, M. S. Improving cancer immunotherapy through nanotechnology. Nat. Rev. Cancer 19, 587–602 (2019).
Google Scholar
Beck, J. D. et al. mRNA therapeutics in cancer immunotherapy. Mol. Cancer 20, 69 (2021).
Google Scholar
Krienke, C. et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 371, 145–153 (2021).
Google Scholar
Wu, K. et al. Preliminary analysis of safety and immunogenicity of a SARS-CoV-2 variant vaccine booster. medRxiv https://www.medrxiv.org/content/10.1101/2021.05.05.21256716v1.full (2021).
Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409–424 (2021).
Google Scholar
Boni, M. F. Vaccination and antigenic drift in influenza. Vaccine 26, C8–C14 (2008).
Google Scholar
Jusu, M. O. et al. Rapid establishment of a cold chain capacity of −60 °C or colder for the STRIVE Ebola vaccine trial during the Ebola outbreak in Sierra Leone. J. Infect. Dis. 217, S48–S55 (2018).
Google Scholar
Panchaud, A., Stojanov, M., Ammerdorffer, A., Vouga, M. & Baud, D. Emerging role of Zika virus in adverse fetal and neonatal outcomes. Clin. Microbiol. Rev. 29, 659–694 (2016).
Google Scholar
Cuevas, J. M., Geller, R., Garijo, R., López-Aldeguer, J. & Sanjuán, R. Extremely high mutation rate of HIV-1 in vivo. PLoS Biol. 13, e1002251 (2015).
Google Scholar
Berndsen, Z. T. et al. Visualization of the HIV-1 Env glycan shield across scales. Proc. Natl Acad. Sci. USA 117, 28014–28025 (2020).
Google Scholar
Kirtane, A. R. et al. Nanotechnology approaches for global infectious diseases. Nat. Nanotechnol. 16, 369–384 (2021).
Google Scholar
Kim, Y. C., Dema, B. & Reyes-Sandoval, A. COVID-19 vaccines: breaking record times to first-in-human trials. NPJ Vaccines 5, 34 (2020).
Google Scholar
Shepherd, S. J., Issadore, D. & Mitchell, M. J. Microfluidic formulation of nanoparticles for biomedical applications. Biomaterials 274, 120826 (2021).
Google Scholar
Belliveau, N. M. et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol. Ther. Nucleic Acids 1, e37 (2012).
Google Scholar

