The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects rema...

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Vydané v:iScience Ročník 24; číslo 12; s. 103479
Hlavní autori: Ndeupen, Sonia, Qin, Zhen, Jacobsen, Sonya, Bouteau, Aurélie, Estanbouli, Henri, Igyártó, Botond Z.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Elsevier Inc 17.12.2021
Elsevier
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ISSN:2589-0042, 2589-0042
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Abstract Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature. [Display omitted] •Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory•The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6•The LNPs' inflammatory properties stem from their ionizable lipid component•The LNPs could be responsible for adjuvanticity and some of the side effects Biological sciences; Immunology; Biotechnology
AbstractList Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature. • Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory • The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6 • The LNPs' inflammatory properties stem from their ionizable lipid component • The LNPs could be responsible for adjuvanticity and some of the side effects Biological sciences; Immunology; Biotechnology
Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.
Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature. [Display omitted] •Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory•The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6•The LNPs' inflammatory properties stem from their ionizable lipid component•The LNPs could be responsible for adjuvanticity and some of the side effects Biological sciences; Immunology; Biotechnology
Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.
ArticleNumber 103479
Author Ndeupen, Sonia
Estanbouli, Henri
Qin, Zhen
Bouteau, Aurélie
Igyártó, Botond Z.
Jacobsen, Sonya
Author_xml – sequence: 1
  givenname: Sonia
  surname: Ndeupen
  fullname: Ndeupen, Sonia
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
– sequence: 2
  givenname: Zhen
  surname: Qin
  fullname: Qin, Zhen
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
– sequence: 3
  givenname: Sonya
  surname: Jacobsen
  fullname: Jacobsen, Sonya
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
– sequence: 4
  givenname: Aurélie
  surname: Bouteau
  fullname: Bouteau, Aurélie
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
– sequence: 5
  givenname: Henri
  surname: Estanbouli
  fullname: Estanbouli, Henri
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
– sequence: 6
  givenname: Botond Z.
  surname: Igyártó
  fullname: Igyártó, Botond Z.
  email: botond.igyarto@jefferson.edu
  organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34841223$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1289/ehp.9030
10.1093/bioinformatics/btr260
10.1016/j.jconrel.2006.04.014
10.1038/s41385-020-0334-2
10.1126/scitranslmed.abh0755
10.1016/S0005-2736(97)00126-0
10.3390/vaccines9010065
10.1038/s41467-018-05482-0
10.1186/s13059-014-0550-8
10.1080/10611860400015936
10.1016/j.jaci.2015.04.001
10.1016/j.addr.2020.06.002
10.1016/j.ymthe.2020.04.018
10.1007/s11745-997-0031-2
10.1001/jama.2021.13443
10.1016/j.addr.2012.05.009
10.1016/j.tox.2005.07.023
10.1016/j.coviro.2021.03.008
10.1093/nar/gkr695
10.1016/j.chom.2011.04.006
10.1073/pnas.0506580102
10.1101/cshperspect.a016295
10.4049/jimmunol.2000549
10.1038/s41586-020-2814-7
10.1001/jamacardio.2021.2833
10.1016/S0378-5173(97)00423-7
10.1056/NEJMoa2027906
10.1016/j.nano.2013.12.003
10.1126/scitranslmed.abd2223
10.1093/nar/28.1.27
10.1038/mt.2008.200
10.1016/j.apsb.2021.02.012
10.1016/j.vaccine.2021.05.087
10.1038/nature21428
10.1084/jem.20171450
10.1038/mt.2010.282
10.3389/fimmu.2020.611337
10.1016/S0264-410X(02)00191-3
10.1002/cpim.45
10.1126/science.abg9857
10.1016/j.immuni.2020.11.009
10.1056/NEJMc2102131
10.1016/j.addr.2020.07.024
10.1186/1756-0500-7-233
10.1371/journal.pone.0223397
10.1016/j.biomaterials.2006.01.038
10.1111/imr.12621
10.1038/s41467-019-12275-6
10.1177/13524585211003476
10.1002/eji.201445127
10.1016/j.jconrel.2015.08.007
10.1542/peds.2021-052478
10.2741/1341
10.1001/jamacardio.2021.2821
10.1038/nri3862
10.1177/0300985817738095
10.1038/s41467-021-23333-3
10.1016/j.drudis.2021.07.021
10.1016/j.celrep.2020.02.111
10.1038/srep34215
10.4103/0976-0105.177703
10.1126/sciimmunol.aaw7083
10.1016/j.molimm.2014.06.038
10.1371/journal.pone.0150606
10.1016/j.immuni.2005.06.008
10.3389/fimmu.2019.01134
10.1016/j.immuni.2020.07.019
10.3389/fimmu.2019.03018
10.1089/nat.2018.0721
10.1002/eji.200737998
10.1023/A:1007504613351
10.1056/NEJMoa2022483
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Immunology
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References Chavda, Vora, Pandya, Patravale (bib10) 2021; 26
Lockman, Koziara, Mumper, Allen (bib44) 2004; 12
Marshall, Ferguson, Lewis, Jaggi, Gagliardo, Collins, Shaughnessya, Carona, Fuss, Corbin (bib50) 2021; 148
Filion, Phillips (bib21) 1998; 162
Montgomery, Ryan, Engler, Hoffman, McClenathan, Collins, Loran, Hrncir, Herring, Platzer (bib54) 2021; 6
Hanson, Fine, Svitak, Faltesek (bib25) 2013
Nair, Jacob (bib55) 2016; 7
Li, Ahmet, Sullivan, Brooks, Kent, De Rose, Salazar, Reis e Sousa, Shortman, Lahoud (bib42) 2015; 45
Szebeni (bib75) 2005; 216
Shirai, Shibuya, Kawai, Tamiya, Munakata, Omata, Suzuki, Aoshi, Yoshioka (bib69) 2020; 10
Gao, Tao, Lu, Zhang, Zhang, Jiang, Fu (bib23) 2006; 27
Lund, Randall (bib48) 2021; 373
Filion, Phillips (bib20) 1997; 1329
Yao, Zurawski, Jarrett, Chicoine, Crabtree, Peterson, Zurawski, Kaplan, Igyártó (bib82) 2015; 136
Kashem, Kaplan (bib34) 2018; 121
Tanaka, Legat, Adam, Steuve, Gatot, Vandenbranden, Ulianov, Lonez, Ruysschaert, Muraille (bib77) 2008; 38
Lonez, Vandenbranden, Ruysschaert (bib45) 2012; 64
Dokka, Toledo, Shi, Castranova, Rojanasakul (bib17) 2000; 17
Khayat-Khoei, Bhattacharyya, Katz, Harrison, Tauhid, Bruso, Houtchens, Edwards, Bakshi (bib36) 2021
Shay, Shimabukuro, DeStefano (bib68) 2021; 6
Wherry, Kurachi (bib81) 2015; 15
Walsh, Frenck, Falsey, Kitchin, Absalon, Gurtman, Lockhart, Neuzil, Mulligan, Bailey (bib80) 2020; 383
Grau-Expósito, Sánchez-Gaona, Massana, Suppi, Astorga-Gamaza, Perea, Rosado, Falcó, Kirkegaard, Torrella (bib24) 2021; 12
Lederer, Castaño, Gómez Atria, Oguin, Wang, Manzoni, Muramatsu, Hogan, Amanat, Cherubin (bib41) 2020; 53
Maugeri, Nawaz, Papadimitriou, Angerfors, Camponeschi, Na, Hölttä, Skantze, Johansson, Sundqvist (bib52) 2019; 10
Conti (bib12) 2004; 9
Kato, Steiner, Park, Hitchcock, Zaid, Hor, Devi, Davey, Vremec, Tullett (bib35) 2020; 205
Lonez, Bessodes, Scherman, Vandenbranden, Escriou, Ruysschaert (bib46) 2014; 10
Kulkarni, Cullis, Van Der Meel (bib38) 2018; 28
Lv, Zhang, Wang, Cui, Yan (bib49) 2006; 114
Boncuk, Kaser, Yu, Taeusch (bib7) 1997; 32
Liberzon, Subramanian, Pinchback, Thorvaldsdottir, Tamayo, Mesirov (bib43) 2011; 27
Samaridou, Heyes, Lutwyche (bib66) 2020; 154–155
Alameh, Weissman, Pardi (bib3) 2020
Comirnaty (bib11) 2021
van Doremalen, Purushotham, Schulz, Holbrook, Bushmaker, Carmody, Port, Yinda, Okumura, Saturday (bib18) 2021; 13
Laczkó, Hogan, Toulmin, Hicks, Lederer, Gaudette, Castaño, Amanat, Muramatsu, Oguin (bib39) 2020; 53
Szebeni (bib76) 2014; 61
Zens, Chen, Farber (bib84) 2019; 1
Love, Huber, Anders (bib47) 2014; 15
Moderna (bib53) 2021
Russell, Moldoveanu, Ogra, Mestecky (bib64) 2020; 11
Dinarello (bib16) 2018; 281
Kozma, Shimizu, Ishida, Szebeni (bib37) 2020; 154–155
Abu Mouch, Roguin, Hellou, Ishai, Shoshan, Mahamid, Zoabi, Aisman, Goldschmid, Berar Yanay (bib1) 2021; 39
Ols, Yang, Thompson, Pushparaj, Tran, Liang, Lin, Eriksson, Karlsson Hedestam, Wyatt (bib58) 2020; 30
Sterlin, Mathian, Miyara, Mohr, Anna, Claër, Quentric, Fadlallah, Devilliers, Ghillani (bib71) 2021; 13
Debin, Kravtzoff, Santiago, Cazales, Sperandio, Melber, Janowicz, Betbeder, Moynier (bib14) 2002; 20
Pardi, Parkhouse, Kirkpatrick, McMahon, Zost, Mui, Tam, Karikó, Barbosa, Madden (bib62) 2018; 9
Sahin, Muik, Derhovanessian, Vogler, Kranz, Vormehr, Baum, Pascal, Quandt, Maurus (bib65) 2020; 586
Freyn, Ramos da Silva, Rosado, Bliss, Pine, Mui, Tam, Madden, de Souza Ferreira, Weissman (bib22) 2020; 28
Swaminathan, Thoryk, Cox, Smith, Wolf, Gindy, Casimiro, Bett (bib74) 2016; 6
Karikó, Muramatsu, Welsh, Ludwig, Kato, Akira, Weissman (bib32) 2008; 16
Patone, Handunnetthi, Saatci, Pan, Katikireddi, Razvi, Hunt, Mei, Dixon, Zaccardi (bib63) 2021
Netea, Quintin, van der Meer (bib57) 2011; 9
Yu, O’Koren, Hotten, Kan, Kopin, Nelson, Que, Gunn (bib83) 2016; 11
Diaz, Parsons, Gering, Meier, Hutchinson, Robicsek (bib15) 2021; 326
Janeway, Travers, Walport, Shlomchik (bib29) 2001
Jackson, Anderson, Rouphael, Roberts, Makhene, Coler, McCullough, Chappell, Denison, Stevens (bib28) 2020; 383
Tao, Mao, Davide, Ng, Cai, Burke, Sachs, Sepp-Lorenzino (bib79) 2011; 19
Karikó, Buckstein, Ni, Weissman (bib31) 2005; 23
Kanehisa (bib30) 2000; 28
Costa, Moreira, Sousa Lobo, Silva (bib13) 2021; 11
Pardi, Hogan, Pelc, Muramatsu, Andersen, DeMaso, Dowd, Sutherland, Scearce, Parks (bib60) 2017; 543
Karikó, Muramatsu, Ludwig, Weissman (bib33) 2011; 39
Awasthi, Hook, Pardi, Wang, Myles, Cancro, Cohen, Weissman, Friedman (bib4) 2019; 4
Shrum, Anantha, Xu, Donnelly, Haeryfar, McCormick, Mele (bib70) 2014; 7
Martins, Sarmento, Ferreira, Souto (bib51) 2007; 2
Elder, Gelein, Silva, Feikert, Opanashuk, Carter, Potter, Maynard, Ito, Finkelstein (bib19) 2006; 114
Blumenthal, Freeman, Saff, Robinson, Wolfson, Foreman, Hashimoto, Banerji, Li, Anvari (bib6) 2021; 384
Subramanian, Tamayo, Mootha, Mukherjee, Ebert, Gillette, Paulovich, Pomeroy, Golub, Lander (bib73) 2005; 102
Pardi, Tuyishime, Muramatsu, Karikó, Mui, Tam, Madden, Hope, Weissman (bib59) 2015; 217
Achiron, Dolev, Menascu, Zohar, Dreyer-Alster, Miron, Shirbint, Magalashvili, Flechter, Givon (bib2) 2021; 27
Ndeupen, Bouteau, Herbst, Qin, Hutchins, Kurup, Diba, Igyártó (bib56) 2021
Su, Bouteau, Cardenas, Uthra, Wang, Smitherman, Gu, Igyártó (bib72) 2020; 15
Bernasconi, Norling, Gribonika, Ong, Burazerovic, Parveen, Schön, Stensson, Bally, Larson (bib5) 2021; 14
Bouteau, Kervevan, Su, Zurawski, Contreras, Dereuddre-Bosquet, Le Grand, Zurawski, Cardinaud, Levy (bib8) 2019; 10
Igyártó, Jacobsen, Ndeupen (bib27) 2021; 48
Tanaka, Narazaki, Kishimoto (bib78) 2014; 6
Pardi, Hogan, Naradikian, Parkhouse, Cain, Jones, Moody, Verkerke, Myles, Willis (bib61) 2018; 215
Sedic, Senn, Lynn, Laska, Smith, Platz, Bolen, Hoge, Bulychev, Jacquinet (bib67) 2018; 55
Buschmann, Carrasco, Alishetty, Paige, Alameh, Weissman (bib9) 2021; 9
Abu Mouch (10.1016/j.isci.2021.103479_bib1) 2021; 39
Igyártó (10.1016/j.isci.2021.103479_bib27) 2021; 48
van Doremalen (10.1016/j.isci.2021.103479_bib18) 2021; 13
Pardi (10.1016/j.isci.2021.103479_bib61) 2018; 215
Zens (10.1016/j.isci.2021.103479_bib84) 2019; 1
Kashem (10.1016/j.isci.2021.103479_bib34) 2018; 121
Russell (10.1016/j.isci.2021.103479_bib64) 2020; 11
Lonez (10.1016/j.isci.2021.103479_bib46) 2014; 10
Pardi (10.1016/j.isci.2021.103479_bib60) 2017; 543
Freyn (10.1016/j.isci.2021.103479_bib22) 2020; 28
Montgomery (10.1016/j.isci.2021.103479_bib54) 2021; 6
Hanson (10.1016/j.isci.2021.103479_bib25) 2013
Tao (10.1016/j.isci.2021.103479_bib79) 2011; 19
Awasthi (10.1016/j.isci.2021.103479_bib4) 2019; 4
Diaz (10.1016/j.isci.2021.103479_bib15) 2021; 326
Jackson (10.1016/j.isci.2021.103479_bib28) 2020; 383
Blumenthal (10.1016/j.isci.2021.103479_bib6) 2021; 384
Laczkó (10.1016/j.isci.2021.103479_bib39) 2020; 53
Marshall (10.1016/j.isci.2021.103479_bib50) 2021; 148
Yao (10.1016/j.isci.2021.103479_bib82) 2015; 136
Nair (10.1016/j.isci.2021.103479_bib55) 2016; 7
Love (10.1016/j.isci.2021.103479_bib47) 2014; 15
Lv (10.1016/j.isci.2021.103479_bib49) 2006; 114
Lonez (10.1016/j.isci.2021.103479_bib45) 2012; 64
Sahin (10.1016/j.isci.2021.103479_bib65) 2020; 586
Lederer (10.1016/j.isci.2021.103479_bib41) 2020; 53
Gao (10.1016/j.isci.2021.103479_bib23) 2006; 27
Su (10.1016/j.isci.2021.103479_bib72) 2020; 15
Bernasconi (10.1016/j.isci.2021.103479_bib5) 2021; 14
Costa (10.1016/j.isci.2021.103479_bib13) 2021; 11
Kulkarni (10.1016/j.isci.2021.103479_bib38) 2018; 28
Shay (10.1016/j.isci.2021.103479_bib68) 2021; 6
Conti (10.1016/j.isci.2021.103479_bib12) 2004; 9
Li (10.1016/j.isci.2021.103479_bib42) 2015; 45
Moderna (10.1016/j.isci.2021.103479_bib53) 2021
Swaminathan (10.1016/j.isci.2021.103479_bib74) 2016; 6
Tanaka (10.1016/j.isci.2021.103479_bib77) 2008; 38
Maugeri (10.1016/j.isci.2021.103479_bib52) 2019; 10
Wherry (10.1016/j.isci.2021.103479_bib81) 2015; 15
Kozma (10.1016/j.isci.2021.103479_bib37) 2020; 154–155
Grau-Expósito (10.1016/j.isci.2021.103479_bib24) 2021; 12
Karikó (10.1016/j.isci.2021.103479_bib32) 2008; 16
Debin (10.1016/j.isci.2021.103479_bib14) 2002; 20
Kato (10.1016/j.isci.2021.103479_bib35) 2020; 205
Lockman (10.1016/j.isci.2021.103479_bib44) 2004; 12
Shirai (10.1016/j.isci.2021.103479_bib69) 2020; 10
Tanaka (10.1016/j.isci.2021.103479_bib78) 2014; 6
Comirnaty (10.1016/j.isci.2021.103479_bib11) 2021
Subramanian (10.1016/j.isci.2021.103479_bib73) 2005; 102
Ndeupen (10.1016/j.isci.2021.103479_bib56) 2021
Pardi (10.1016/j.isci.2021.103479_bib62) 2018; 9
Bouteau (10.1016/j.isci.2021.103479_bib8) 2019; 10
Filion (10.1016/j.isci.2021.103479_bib20) 1997; 1329
Filion (10.1016/j.isci.2021.103479_bib21) 1998; 162
Kanehisa (10.1016/j.isci.2021.103479_bib30) 2000; 28
Boncuk (10.1016/j.isci.2021.103479_bib7) 1997; 32
Martins (10.1016/j.isci.2021.103479_bib51) 2007; 2
Sedic (10.1016/j.isci.2021.103479_bib67) 2018; 55
Alameh (10.1016/j.isci.2021.103479_bib3) 2020
Szebeni (10.1016/j.isci.2021.103479_bib75) 2005; 216
Liberzon (10.1016/j.isci.2021.103479_bib43) 2011; 27
Khayat-Khoei (10.1016/j.isci.2021.103479_bib36) 2021
Karikó (10.1016/j.isci.2021.103479_bib31) 2005; 23
Netea (10.1016/j.isci.2021.103479_bib57) 2011; 9
Achiron (10.1016/j.isci.2021.103479_bib2) 2021; 27
Samaridou (10.1016/j.isci.2021.103479_bib66) 2020; 154–155
Dokka (10.1016/j.isci.2021.103479_bib17) 2000; 17
Szebeni (10.1016/j.isci.2021.103479_bib76) 2014; 61
Walsh (10.1016/j.isci.2021.103479_bib80) 2020; 383
Elder (10.1016/j.isci.2021.103479_bib19) 2006; 114
Yu (10.1016/j.isci.2021.103479_bib83) 2016; 11
Lund (10.1016/j.isci.2021.103479_bib48) 2021; 373
Buschmann (10.1016/j.isci.2021.103479_bib9) 2021; 9
Dinarello (10.1016/j.isci.2021.103479_bib16) 2018; 281
Ols (10.1016/j.isci.2021.103479_bib58) 2020; 30
Chavda (10.1016/j.isci.2021.103479_bib10) 2021; 26
Janeway (10.1016/j.isci.2021.103479_bib29) 2001
Karikó (10.1016/j.isci.2021.103479_bib33) 2011; 39
Patone (10.1016/j.isci.2021.103479_bib63) 2021
Pardi (10.1016/j.isci.2021.103479_bib59) 2015; 217
Shrum (10.1016/j.isci.2021.103479_bib70) 2014; 7
Sterlin (10.1016/j.isci.2021.103479_bib71) 2021; 13
33688649 - bioRxiv. 2021 Jul 23
References_xml – start-page: e4440
  year: 2013
  ident: bib25
  article-title: Intranasal administration of CNS Therapeutics to awake mice
  publication-title: J. Vis. Exp.
– volume: 205
  start-page: 1842
  year: 2020
  end-page: 1856
  ident: bib35
  article-title: Display of native antigen on cDC1 that have spatial access to both T and B cells underlies efficient humoral vaccination
  publication-title: J. Immunol.
– volume: 102
  start-page: 15545
  year: 2005
  end-page: 15550
  ident: bib73
  article-title: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 27
  start-page: 3482
  year: 2006
  end-page: 3490
  ident: bib23
  article-title: Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration
  publication-title: Biomaterials
– volume: 136
  start-page: 1387
  year: 2015
  end-page: 1397.e7
  ident: bib82
  article-title: Skin dendritic cells induce follicular helper T cells and protective humoral immune responses
  publication-title: J. Allergy Clin. Immunol.
– volume: 9
  start-page: 1
  year: 2021
  end-page: 30
  ident: bib9
  article-title: Nanomaterial delivery systems for mrna vaccines
  publication-title: Vaccines
– volume: 53
  start-page: 1281
  year: 2020
  end-page: 1295.e5
  ident: bib41
  article-title: SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation
  publication-title: Immunity
– volume: 7
  start-page: 27
  year: 2016
  ident: bib55
  article-title: A simple practice guide for dose conversion between animals and human
  publication-title: J. Basic Clin. Pharm.
– volume: 28
  start-page: 1569
  year: 2020
  end-page: 1584
  ident: bib22
  article-title: A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice
  publication-title: Mol. Ther.
– volume: 2
  start-page: 595
  year: 2007
  end-page: 607
  ident: bib51
  article-title: Lipid-based colloidal carriers for peptide and protein delivery--liposomes versus lipid nanoparticles
  publication-title: Int. J. Nanomed.
– volume: 13
  start-page: 2223
  year: 2021
  ident: bib71
  article-title: IgA dominates the early neutralizing antibody response to SARS-CoV-2
  publication-title: Sci. Transl. Med.
– volume: 586
  start-page: 594
  year: 2020
  end-page: 599
  ident: bib65
  article-title: COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses
  publication-title: Nature
– volume: 6
  start-page: 34215
  year: 2016
  ident: bib74
  article-title: A tetravalent sub-unit dengue vaccine formulated with ionizable cationic lipid nanoparticle induces significant immune responses in rodents and non-human primates
  publication-title: Sci. Rep.
– volume: 10
  start-page: 1134
  year: 2019
  ident: bib8
  article-title: DC subsets regulate humoral immune responses by supporting the differentiation of distinct Tfh cells
  publication-title: Front. Immunol.
– volume: 6
  start-page: 1115
  year: 2021
  end-page: 1117
  ident: bib68
  article-title: Myocarditis occurring after immunization with mRNA-based COVID-19 vaccines
  publication-title: JAMA Cardiol.
– volume: 10
  start-page: 4333
  year: 2019
  ident: bib52
  article-title: Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells
  publication-title: Nat. Commun.
– volume: 19
  start-page: 567
  year: 2011
  end-page: 575
  ident: bib79
  article-title: Mechanistically probing lipid-sirna nanoparticle-associated toxicities identifies jak inhibitors effective in mitigating multifaceted toxic responses
  publication-title: Mol. Ther.
– volume: 39
  start-page: e142
  year: 2011
  ident: bib33
  article-title: Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA
  publication-title: Nucleic Acids Res.
– volume: 154–155
  start-page: 163
  year: 2020
  end-page: 175
  ident: bib37
  article-title: Anti-PEG antibodies: properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals
  publication-title: Adv. Drug Deliv. Rev.
– volume: 16
  start-page: 1833
  year: 2008
  end-page: 1840
  ident: bib32
  article-title: Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability
  publication-title: Mol. Ther.
– volume: 384
  start-page: 1273
  year: 2021
  end-page: 1277
  ident: bib6
  article-title: Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2
  publication-title: N. Engl. J. Med.
– start-page: 1
  year: 2021
  end-page: 169
  ident: bib53
  article-title: Assessment Report COVID-19 Vaccine Moderna Common. EMA/15689/2021 Corr.1∗1 31
– volume: 45
  start-page: 854
  year: 2015
  end-page: 864
  ident: bib42
  article-title: Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates
  publication-title: Eur. J. Immunol.
– start-page: 636
  year: 2001
  end-page: 654
  ident: bib29
  article-title: Self-tolerance and its loss
  publication-title: Immunobiology: The Immune System in Health and Disease
– year: 2021
  ident: bib56
  article-title: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses
  publication-title: BioRxiv Prepr. Serv. Biol.
– volume: 11
  start-page: 611337
  year: 2020
  ident: bib64
  article-title: Mucosal immunity in COVID-19: a neglected but critical aspect of SARS-CoV-2 infection
  publication-title: Front. Immunol.
– volume: 383
  start-page: 1920
  year: 2020
  end-page: 1931
  ident: bib28
  article-title: An mRNA vaccine against SARS-CoV-2 — preliminary report
  publication-title: N. Engl. J. Med.
– volume: 1329
  start-page: 345
  year: 1997
  end-page: 356
  ident: bib20
  article-title: Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells
  publication-title: Biochim. Biophys. Acta. Biomembr.
– volume: 6
  start-page: a016295
  year: 2014
  ident: bib78
  article-title: IL-6 in inflammation, immunity, and disease
  publication-title: Cold Spring Harb. Perspect. Biol.
– year: 2021
  ident: bib36
  article-title: COVID-19 mRNA vaccination leading to CNS inflammation: a case series
  publication-title: J. Neurol.
– volume: 20
  start-page: 2752
  year: 2002
  end-page: 2763
  ident: bib14
  article-title: Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses
  publication-title: Vaccine
– volume: 11
  start-page: e0150606
  year: 2016
  ident: bib83
  article-title: A protocol for the comprehensive flow cytometric analysis of immune cells in normal and inflamed murine non-lymphoid tissues
  publication-title: PLoS One
– volume: 12
  start-page: 3010
  year: 2021
  ident: bib24
  article-title: Peripheral and lung resident memory T cell responses against SARS-CoV-2
  publication-title: Nat. Commun.
– volume: 121
  start-page: e45
  year: 2018
  ident: bib34
  article-title: Isolation of murine skin resident and migratory dendritic cells via enzymatic digestion
  publication-title: Curr. Protoc. Immunol.
– volume: 39
  start-page: 3790
  year: 2021
  end-page: 3793
  ident: bib1
  article-title: Myocarditis following COVID-19 mRNA vaccination
  publication-title: Vaccine
– volume: 30
  start-page: 3964
  year: 2020
  end-page: 3971.e7
  ident: bib58
  article-title: Route of vaccine administration alters antigen trafficking but not innate or adaptive immunity
  publication-title: Cell Rep.
– start-page: 1
  year: 2021
  end-page: 140
  ident: bib11
  article-title: Assessment Report COVID-19 Vaccine Comirnaty. EMA/707383/2020 Corr.1∗ 31
– volume: 28
  start-page: 27
  year: 2000
  end-page: 30
  ident: bib30
  article-title: KEGG: kyoto encyclopedia of genes and genomes
  publication-title: Nucleic Acids Res.
– volume: 281
  start-page: 8
  year: 2018
  end-page: 27
  ident: bib16
  article-title: Overview of the IL-1 family in innate inflammation and acquired immunity
  publication-title: Immunol. Rev.
– volume: 10
  start-page: 775
  year: 2014
  end-page: 782
  ident: bib46
  article-title: Cationic lipid nanocarriers activate Toll-like receptor 2 and NLRP3 inflammasome pathways
  publication-title: Nanomed. Nanotechnol. Biol. Med.
– volume: 7
  start-page: 233
  year: 2014
  ident: bib70
  article-title: A robust scoring system to evaluate sepsis severity in an animal model
  publication-title: BMC Res. Notes
– volume: 12
  start-page: 635
  year: 2004
  end-page: 641
  ident: bib44
  article-title: Nanoparticle surface charges alter blood–brain barrier integrity and permeability
  publication-title: J. Drug Target.
– volume: 26
  start-page: 2619
  year: 2021
  end-page: 2636
  ident: bib10
  article-title: Intranasal vaccines for SARS-CoV-2: from challenges to potential in COVID-19 management
  publication-title: Drug Discov. Today
– volume: 14
  start-page: 523
  year: 2021
  end-page: 536
  ident: bib5
  article-title: A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection
  publication-title: Mucosal Immunol.
– volume: 9
  start-page: 1433
  year: 2004
  ident: bib12
  article-title: Cytokines and fever
  publication-title: Front. Biosci.
– volume: 64
  start-page: 1749
  year: 2012
  end-page: 1758
  ident: bib45
  article-title: Cationic lipids activate intracellular signaling pathways
  publication-title: Adv. Drug Deliv. Rev.
– volume: 326
  start-page: 1210
  year: 2021
  end-page: 1212
  ident: bib15
  article-title: Myocarditis and pericarditis after vaccination for COVID-19
  publication-title: JAMA
– volume: 15
  start-page: 486
  year: 2015
  end-page: 499
  ident: bib81
  article-title: Molecular and cellular insights into T cell exhaustion
  publication-title: Nat. Rev. Immunol.
– volume: 1
  start-page: e85832
  year: 2019
  ident: bib84
  article-title: Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection
  publication-title: JCI Insight
– volume: 11
  start-page: 925
  year: 2021
  end-page: 940
  ident: bib13
  article-title: Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: a current overview of in vivo studies
  publication-title: Acta Pharm. Sin. B
– volume: 154–155
  start-page: 37
  year: 2020
  end-page: 63
  ident: bib66
  article-title: Lipid nanoparticles for nucleic acid delivery: current perspectives
  publication-title: Adv. Drug Deliv. Rev.
– volume: 162
  start-page: 159
  year: 1998
  end-page: 170
  ident: bib21
  article-title: Major Limitations in the Use of Cationic Liposomes for DNA Delivery
  publication-title: Int. J. Pharm.
– year: 2021
  ident: bib63
  article-title: Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection
  publication-title: Nat. Med.
– volume: 217
  start-page: 345
  year: 2015
  end-page: 351
  ident: bib59
  article-title: Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes
  publication-title: J. Control Release
– volume: 216
  start-page: 106
  year: 2005
  end-page: 121
  ident: bib75
  article-title: Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity
  publication-title: Toxicology
– volume: 13
  start-page: eabh0755
  year: 2021
  ident: bib18
  article-title: Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models
  publication-title: Sci. Transl. Med.
– volume: 543
  start-page: 248
  year: 2017
  end-page: 251
  ident: bib60
  article-title: Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
  publication-title: Nature
– volume: 15
  start-page: 550
  year: 2014
  ident: bib47
  article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
  publication-title: Genome Biol.
– volume: 114
  start-page: 100
  year: 2006
  end-page: 109
  ident: bib49
  article-title: Toxicity of cationic lipids and cationic polymers in gene delivery
  publication-title: J. Control Release
– volume: 27
  start-page: 864
  year: 2021
  end-page: 870
  ident: bib2
  article-title: COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021
  publication-title: Mult. Scler. J.
– volume: 53
  start-page: 724
  year: 2020
  end-page: 732.e7
  ident: bib39
  article-title: A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice
  publication-title: Immunity
– volume: 215
  start-page: 1571
  year: 2018
  end-page: 1588
  ident: bib61
  article-title: Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
  publication-title: J. Exp. Med.
– volume: 55
  start-page: 341
  year: 2018
  end-page: 354
  ident: bib67
  article-title: Safety evaluation of lipid nanoparticle–formulated modified mRNA in the sprague-dawley rat and cynomolgus monkey
  publication-title: Vet. Pathol.
– volume: 17
  start-page: 521
  year: 2000
  end-page: 525
  ident: bib17
  article-title: Oxygen Radical-Mediated Pulmonary lack of immunogenicity, simplicity and ease of production make
  publication-title: Pharm. Res.
– volume: 148
  year: 2021
  ident: bib50
  article-title: Symptomatic acute myocarditis in seven adolescents following pfizer-BioNTech COVID-19 vaccination
  publication-title: Pediatrics
– volume: 9
  start-page: 355
  year: 2011
  end-page: 361
  ident: bib57
  article-title: Trained immunity: a memory for innate host defense
  publication-title: Cell Host Microbe.
– start-page: 1
  year: 2020
  end-page: 35
  ident: bib3
  article-title: Messenger RNA-based vaccines against infectious diseases
  publication-title: Curr. Top. Microbiol. Immunol.
– volume: 15
  start-page: e0223397
  year: 2020
  ident: bib72
  article-title: Brief communication: long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells
  publication-title: PLoS One
– volume: 61
  start-page: 163
  year: 2014
  end-page: 173
  ident: bib76
  article-title: Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals
  publication-title: Mol. Immunol.
– volume: 38
  start-page: 1351
  year: 2008
  end-page: 1357
  ident: bib77
  article-title: DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4
  publication-title: Eur. J. Immunol.
– volume: 48
  start-page: 65
  year: 2021
  end-page: 72
  ident: bib27
  article-title: Future considerations for the mRNA-lipid nanoparticle vaccine platform
  publication-title: Curr. Opin. Virol.
– volume: 27
  start-page: 1739
  year: 2011
  end-page: 1740
  ident: bib43
  article-title: Molecular signatures database (MSigDB) 3.0
  publication-title: Bioinformatics
– volume: 4
  start-page: eaaw7083
  year: 2019
  ident: bib4
  article-title: Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes
  publication-title: Sci. Immunol.
– volume: 114
  start-page: 1172
  year: 2006
  end-page: 1178
  ident: bib19
  article-title: Translocation of inhaled ultrafine manganese oxide particles to the central nervous system
  publication-title: Environ. Health Perspect.
– volume: 6
  start-page: 1202
  year: 2021
  end-page: 1206
  ident: bib54
  article-title: Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military
  publication-title: JAMA Cardiol.
– volume: 28
  start-page: 146
  year: 2018
  end-page: 157
  ident: bib38
  article-title: Lipid nanoparticles enabling gene therapies: from concepts to clinical utility
  publication-title: Nucleic Acid Ther.
– volume: 373
  start-page: 397
  year: 2021
  end-page: 399
  ident: bib48
  article-title: Scent of a vaccine
  publication-title: Science
– volume: 23
  start-page: 165
  year: 2005
  end-page: 175
  ident: bib31
  article-title: Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA
  publication-title: Immunity
– volume: 32
  start-page: 247
  year: 1997
  end-page: 253
  ident: bib7
  article-title: Effects of cationic liposome-DNA complexes on pulmonary surfactant function in vitro and in vivo
  publication-title: Lipids
– volume: 10
  start-page: 3018
  year: 2020
  ident: bib69
  article-title: Lipid nanoparticles potentiate CpG-oligodeoxynucleotide-based vaccine for influenza virus
  publication-title: Front. Immunol.
– volume: 9
  start-page: 3361
  year: 2018
  ident: bib62
  article-title: Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies
  publication-title: Nat. Commun.
– volume: 383
  start-page: 2439
  year: 2020
  end-page: 2450
  ident: bib80
  article-title: Safety and immunogenicity of two RNA-based covid-19 vaccine candidates
  publication-title: N. Engl. J. Med.
– volume: 114
  start-page: 1172
  year: 2006
  ident: 10.1016/j.isci.2021.103479_bib19
  article-title: Translocation of inhaled ultrafine manganese oxide particles to the central nervous system
  publication-title: Environ. Health Perspect.
  doi: 10.1289/ehp.9030
– volume: 27
  start-page: 1739
  year: 2011
  ident: 10.1016/j.isci.2021.103479_bib43
  article-title: Molecular signatures database (MSigDB) 3.0
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btr260
– volume: 114
  start-page: 100
  year: 2006
  ident: 10.1016/j.isci.2021.103479_bib49
  article-title: Toxicity of cationic lipids and cationic polymers in gene delivery
  publication-title: J. Control Release
  doi: 10.1016/j.jconrel.2006.04.014
– volume: 14
  start-page: 523
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib5
  article-title: A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection
  publication-title: Mucosal Immunol.
  doi: 10.1038/s41385-020-0334-2
– volume: 13
  start-page: eabh0755
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib18
  article-title: Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.abh0755
– volume: 1329
  start-page: 345
  year: 1997
  ident: 10.1016/j.isci.2021.103479_bib20
  article-title: Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells
  publication-title: Biochim. Biophys. Acta. Biomembr.
  doi: 10.1016/S0005-2736(97)00126-0
– volume: 9
  start-page: 1
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib9
  article-title: Nanomaterial delivery systems for mrna vaccines
  publication-title: Vaccines
  doi: 10.3390/vaccines9010065
– volume: 9
  start-page: 3361
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib62
  article-title: Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-05482-0
– volume: 15
  start-page: 550
  year: 2014
  ident: 10.1016/j.isci.2021.103479_bib47
  article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
  publication-title: Genome Biol.
  doi: 10.1186/s13059-014-0550-8
– volume: 12
  start-page: 635
  year: 2004
  ident: 10.1016/j.isci.2021.103479_bib44
  article-title: Nanoparticle surface charges alter blood–brain barrier integrity and permeability
  publication-title: J. Drug Target.
  doi: 10.1080/10611860400015936
– volume: 136
  start-page: 1387
  year: 2015
  ident: 10.1016/j.isci.2021.103479_bib82
  article-title: Skin dendritic cells induce follicular helper T cells and protective humoral immune responses
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/j.jaci.2015.04.001
– volume: 154–155
  start-page: 37
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib66
  article-title: Lipid nanoparticles for nucleic acid delivery: current perspectives
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/j.addr.2020.06.002
– volume: 28
  start-page: 1569
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib22
  article-title: A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2020.04.018
– volume: 32
  start-page: 247
  year: 1997
  ident: 10.1016/j.isci.2021.103479_bib7
  article-title: Effects of cationic liposome-DNA complexes on pulmonary surfactant function in vitro and in vivo
  publication-title: Lipids
  doi: 10.1007/s11745-997-0031-2
– volume: 326
  start-page: 1210
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib15
  article-title: Myocarditis and pericarditis after vaccination for COVID-19
  publication-title: JAMA
  doi: 10.1001/jama.2021.13443
– start-page: 1
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib53
– volume: 64
  start-page: 1749
  year: 2012
  ident: 10.1016/j.isci.2021.103479_bib45
  article-title: Cationic lipids activate intracellular signaling pathways
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/j.addr.2012.05.009
– volume: 216
  start-page: 106
  year: 2005
  ident: 10.1016/j.isci.2021.103479_bib75
  article-title: Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity
  publication-title: Toxicology
  doi: 10.1016/j.tox.2005.07.023
– volume: 48
  start-page: 65
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib27
  article-title: Future considerations for the mRNA-lipid nanoparticle vaccine platform
  publication-title: Curr. Opin. Virol.
  doi: 10.1016/j.coviro.2021.03.008
– start-page: 1
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib3
  article-title: Messenger RNA-based vaccines against infectious diseases
  publication-title: Curr. Top. Microbiol. Immunol.
– volume: 39
  start-page: e142
  year: 2011
  ident: 10.1016/j.isci.2021.103479_bib33
  article-title: Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkr695
– volume: 9
  start-page: 355
  year: 2011
  ident: 10.1016/j.isci.2021.103479_bib57
  article-title: Trained immunity: a memory for innate host defense
  publication-title: Cell Host Microbe.
  doi: 10.1016/j.chom.2011.04.006
– volume: 102
  start-page: 15545
  year: 2005
  ident: 10.1016/j.isci.2021.103479_bib73
  article-title: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.0506580102
– volume: 6
  start-page: a016295
  year: 2014
  ident: 10.1016/j.isci.2021.103479_bib78
  article-title: IL-6 in inflammation, immunity, and disease
  publication-title: Cold Spring Harb. Perspect. Biol.
  doi: 10.1101/cshperspect.a016295
– volume: 205
  start-page: 1842
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib35
  article-title: Display of native antigen on cDC1 that have spatial access to both T and B cells underlies efficient humoral vaccination
  publication-title: J. Immunol.
  doi: 10.4049/jimmunol.2000549
– volume: 586
  start-page: 594
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib65
  article-title: COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses
  publication-title: Nature
  doi: 10.1038/s41586-020-2814-7
– volume: 6
  start-page: 1202
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib54
  article-title: Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military
  publication-title: JAMA Cardiol.
  doi: 10.1001/jamacardio.2021.2833
– volume: 162
  start-page: 159
  year: 1998
  ident: 10.1016/j.isci.2021.103479_bib21
  article-title: Major Limitations in the Use of Cationic Liposomes for DNA Delivery
  publication-title: Int. J. Pharm.
  doi: 10.1016/S0378-5173(97)00423-7
– volume: 383
  start-page: 2439
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib80
  article-title: Safety and immunogenicity of two RNA-based covid-19 vaccine candidates
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa2027906
– volume: 10
  start-page: 775
  year: 2014
  ident: 10.1016/j.isci.2021.103479_bib46
  article-title: Cationic lipid nanocarriers activate Toll-like receptor 2 and NLRP3 inflammasome pathways
  publication-title: Nanomed. Nanotechnol. Biol. Med.
  doi: 10.1016/j.nano.2013.12.003
– volume: 13
  start-page: 2223
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib71
  article-title: IgA dominates the early neutralizing antibody response to SARS-CoV-2
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.abd2223
– volume: 28
  start-page: 27
  year: 2000
  ident: 10.1016/j.isci.2021.103479_bib30
  article-title: KEGG: kyoto encyclopedia of genes and genomes
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/28.1.27
– start-page: 1
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib11
– volume: 16
  start-page: 1833
  year: 2008
  ident: 10.1016/j.isci.2021.103479_bib32
  article-title: Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2008.200
– year: 2021
  ident: 10.1016/j.isci.2021.103479_bib63
  article-title: Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection
  publication-title: Nat. Med.
– volume: 11
  start-page: 925
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib13
  article-title: Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: a current overview of in vivo studies
  publication-title: Acta Pharm. Sin. B
  doi: 10.1016/j.apsb.2021.02.012
– volume: 39
  start-page: 3790
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib1
  article-title: Myocarditis following COVID-19 mRNA vaccination
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2021.05.087
– volume: 543
  start-page: 248
  year: 2017
  ident: 10.1016/j.isci.2021.103479_bib60
  article-title: Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
  publication-title: Nature
  doi: 10.1038/nature21428
– year: 2021
  ident: 10.1016/j.isci.2021.103479_bib36
  article-title: COVID-19 mRNA vaccination leading to CNS inflammation: a case series
  publication-title: J. Neurol.
– volume: 215
  start-page: 1571
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib61
  article-title: Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
  publication-title: J. Exp. Med.
  doi: 10.1084/jem.20171450
– volume: 19
  start-page: 567
  year: 2011
  ident: 10.1016/j.isci.2021.103479_bib79
  article-title: Mechanistically probing lipid-sirna nanoparticle-associated toxicities identifies jak inhibitors effective in mitigating multifaceted toxic responses
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2010.282
– volume: 11
  start-page: 611337
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib64
  article-title: Mucosal immunity in COVID-19: a neglected but critical aspect of SARS-CoV-2 infection
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2020.611337
– volume: 20
  start-page: 2752
  year: 2002
  ident: 10.1016/j.isci.2021.103479_bib14
  article-title: Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses
  publication-title: Vaccine
  doi: 10.1016/S0264-410X(02)00191-3
– volume: 121
  start-page: e45
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib34
  article-title: Isolation of murine skin resident and migratory dendritic cells via enzymatic digestion
  publication-title: Curr. Protoc. Immunol.
  doi: 10.1002/cpim.45
– volume: 373
  start-page: 397
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib48
  article-title: Scent of a vaccine
  publication-title: Science
  doi: 10.1126/science.abg9857
– volume: 53
  start-page: 1281
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib41
  article-title: SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation
  publication-title: Immunity
  doi: 10.1016/j.immuni.2020.11.009
– volume: 384
  start-page: 1273
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib6
  article-title: Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMc2102131
– volume: 154–155
  start-page: 163
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib37
  article-title: Anti-PEG antibodies: properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/j.addr.2020.07.024
– volume: 7
  start-page: 233
  year: 2014
  ident: 10.1016/j.isci.2021.103479_bib70
  article-title: A robust scoring system to evaluate sepsis severity in an animal model
  publication-title: BMC Res. Notes
  doi: 10.1186/1756-0500-7-233
– volume: 15
  start-page: e0223397
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib72
  article-title: Brief communication: long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0223397
– volume: 27
  start-page: 3482
  year: 2006
  ident: 10.1016/j.isci.2021.103479_bib23
  article-title: Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration
  publication-title: Biomaterials
  doi: 10.1016/j.biomaterials.2006.01.038
– volume: 281
  start-page: 8
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib16
  article-title: Overview of the IL-1 family in innate inflammation and acquired immunity
  publication-title: Immunol. Rev.
  doi: 10.1111/imr.12621
– volume: 10
  start-page: 4333
  year: 2019
  ident: 10.1016/j.isci.2021.103479_bib52
  article-title: Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-019-12275-6
– volume: 27
  start-page: 864
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib2
  article-title: COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021
  publication-title: Mult. Scler. J.
  doi: 10.1177/13524585211003476
– volume: 45
  start-page: 854
  year: 2015
  ident: 10.1016/j.isci.2021.103479_bib42
  article-title: Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates
  publication-title: Eur. J. Immunol.
  doi: 10.1002/eji.201445127
– volume: 217
  start-page: 345
  year: 2015
  ident: 10.1016/j.isci.2021.103479_bib59
  article-title: Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes
  publication-title: J. Control Release
  doi: 10.1016/j.jconrel.2015.08.007
– volume: 148
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib50
  article-title: Symptomatic acute myocarditis in seven adolescents following pfizer-BioNTech COVID-19 vaccination
  publication-title: Pediatrics
  doi: 10.1542/peds.2021-052478
– volume: 9
  start-page: 1433
  year: 2004
  ident: 10.1016/j.isci.2021.103479_bib12
  article-title: Cytokines and fever
  publication-title: Front. Biosci.
  doi: 10.2741/1341
– start-page: 636
  year: 2001
  ident: 10.1016/j.isci.2021.103479_bib29
  article-title: Self-tolerance and its loss
– volume: 6
  start-page: 1115
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib68
  article-title: Myocarditis occurring after immunization with mRNA-based COVID-19 vaccines
  publication-title: JAMA Cardiol.
  doi: 10.1001/jamacardio.2021.2821
– volume: 15
  start-page: 486
  year: 2015
  ident: 10.1016/j.isci.2021.103479_bib81
  article-title: Molecular and cellular insights into T cell exhaustion
  publication-title: Nat. Rev. Immunol.
  doi: 10.1038/nri3862
– volume: 55
  start-page: 341
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib67
  article-title: Safety evaluation of lipid nanoparticle–formulated modified mRNA in the sprague-dawley rat and cynomolgus monkey
  publication-title: Vet. Pathol.
  doi: 10.1177/0300985817738095
– volume: 12
  start-page: 3010
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib24
  article-title: Peripheral and lung resident memory T cell responses against SARS-CoV-2
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-23333-3
– volume: 26
  start-page: 2619
  year: 2021
  ident: 10.1016/j.isci.2021.103479_bib10
  article-title: Intranasal vaccines for SARS-CoV-2: from challenges to potential in COVID-19 management
  publication-title: Drug Discov. Today
  doi: 10.1016/j.drudis.2021.07.021
– volume: 30
  start-page: 3964
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib58
  article-title: Route of vaccine administration alters antigen trafficking but not innate or adaptive immunity
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2020.02.111
– start-page: e4440
  year: 2013
  ident: 10.1016/j.isci.2021.103479_bib25
  article-title: Intranasal administration of CNS Therapeutics to awake mice
  publication-title: J. Vis. Exp.
– volume: 6
  start-page: 34215
  year: 2016
  ident: 10.1016/j.isci.2021.103479_bib74
  article-title: A tetravalent sub-unit dengue vaccine formulated with ionizable cationic lipid nanoparticle induces significant immune responses in rodents and non-human primates
  publication-title: Sci. Rep.
  doi: 10.1038/srep34215
– volume: 7
  start-page: 27
  year: 2016
  ident: 10.1016/j.isci.2021.103479_bib55
  article-title: A simple practice guide for dose conversion between animals and human
  publication-title: J. Basic Clin. Pharm.
  doi: 10.4103/0976-0105.177703
– volume: 4
  start-page: eaaw7083
  year: 2019
  ident: 10.1016/j.isci.2021.103479_bib4
  article-title: Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes
  publication-title: Sci. Immunol.
  doi: 10.1126/sciimmunol.aaw7083
– volume: 61
  start-page: 163
  year: 2014
  ident: 10.1016/j.isci.2021.103479_bib76
  article-title: Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals
  publication-title: Mol. Immunol.
  doi: 10.1016/j.molimm.2014.06.038
– volume: 11
  start-page: e0150606
  year: 2016
  ident: 10.1016/j.isci.2021.103479_bib83
  article-title: A protocol for the comprehensive flow cytometric analysis of immune cells in normal and inflamed murine non-lymphoid tissues
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0150606
– volume: 23
  start-page: 165
  year: 2005
  ident: 10.1016/j.isci.2021.103479_bib31
  article-title: Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA
  publication-title: Immunity
  doi: 10.1016/j.immuni.2005.06.008
– volume: 10
  start-page: 1134
  year: 2019
  ident: 10.1016/j.isci.2021.103479_bib8
  article-title: DC subsets regulate humoral immune responses by supporting the differentiation of distinct Tfh cells
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2019.01134
– volume: 53
  start-page: 724
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib39
  article-title: A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice
  publication-title: Immunity
  doi: 10.1016/j.immuni.2020.07.019
– volume: 2
  start-page: 595
  year: 2007
  ident: 10.1016/j.isci.2021.103479_bib51
  article-title: Lipid-based colloidal carriers for peptide and protein delivery--liposomes versus lipid nanoparticles
  publication-title: Int. J. Nanomed.
– year: 2021
  ident: 10.1016/j.isci.2021.103479_bib56
  article-title: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses
  publication-title: BioRxiv Prepr. Serv. Biol.
– volume: 10
  start-page: 3018
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib69
  article-title: Lipid nanoparticles potentiate CpG-oligodeoxynucleotide-based vaccine for influenza virus
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2019.03018
– volume: 1
  start-page: e85832
  year: 2019
  ident: 10.1016/j.isci.2021.103479_bib84
  article-title: Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection
  publication-title: JCI Insight
– volume: 28
  start-page: 146
  year: 2018
  ident: 10.1016/j.isci.2021.103479_bib38
  article-title: Lipid nanoparticles enabling gene therapies: from concepts to clinical utility
  publication-title: Nucleic Acid Ther.
  doi: 10.1089/nat.2018.0721
– volume: 38
  start-page: 1351
  year: 2008
  ident: 10.1016/j.isci.2021.103479_bib77
  article-title: DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4
  publication-title: Eur. J. Immunol.
  doi: 10.1002/eji.200737998
– volume: 17
  start-page: 521
  year: 2000
  ident: 10.1016/j.isci.2021.103479_bib17
  article-title: Oxygen Radical-Mediated Pulmonary lack of immunogenicity, simplicity and ease of production make
  publication-title: Pharm. Res.
  doi: 10.1023/A:1007504613351
– volume: 383
  start-page: 1920
  year: 2020
  ident: 10.1016/j.isci.2021.103479_bib28
  article-title: An mRNA vaccine against SARS-CoV-2 — preliminary report
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa2022483
– reference: 33688649 - bioRxiv. 2021 Jul 23;:
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Snippet Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and...
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SubjectTerms Biological sciences
Biotechnology
Immunology
Title The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
URI https://dx.doi.org/10.1016/j.isci.2021.103479
https://www.ncbi.nlm.nih.gov/pubmed/34841223
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