Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen
Source abstract
Abstract
High Resolution Image Download MS PowerPoint Slide Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae . Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: RNA Interference and Gene Delivery · SARS-CoV-2 and COVID-19 Research · Immunotherapy and Immune Responses
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Laboratory of Drug and Gene Delivery Research, Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan
Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Center for Advanced Modalities and DDS, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Center for Infectious Disease Education and Research, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Global Center for Medical Engineering and Informatics, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Funding
Osaka University · BIKEN Foundation · Japan Agency for Medical Research and Development · Nippon Foundation · Ministry of Education, Culture, Sports, Science and Technology
References (95)
Show source-provided references
1. 10.1056/NEJMoa211618510.1056/NEJMoa2116185 ↗
2. 10.1056/NEJMoa210765910.1056/NEJMoa2107659 ↗
3. 10.1056/NEJMoa202790610.1056/NEJMoa2027906 ↗
4. 10.1056/NEJMoa210154410.1056/NEJMoa2101544 ↗
5. 10.1016/j.cell.2022.05.02210.1016/j.cell.2022.05.022 ↗
6. 10.3390/vaccines1009149810.3390/vaccines10091498 ↗
7. 10.3390/biom1108107210.3390/biom11081072 ↗
8. 10.1126/scitranslmed.abd152510.1126/scitranslmed.abd1525 ↗
9. 10.1126/scitranslmed.abj530510.1126/scitranslmed.abj5305 ↗
10. 10.1016/j.smim.2018.05.00110.1016/j.smim.2018.05.001 ↗
11. 10.1073/pnas.140047211110.1073/pnas.1400472111 ↗
12. 10.1007/s11906-018-0820-z10.1007/s11906-018-0820-z ↗
13. 10.1038/s41541-018-0089-x10.1038/s41541-018-0089-x ↗
14. 10.1016/j.coi.2013.12.00710.1016/j.coi.2013.12.007 ↗
15. 10.1038/s41573-021-00163-y10.1038/s41573-021-00163-y ↗
16. 10.1038/nature1315710.1038/nature13157 ↗
17. 10.4049/jimmunol.130149010.4049/jimmunol.1301490 ↗
18. 10.4049/jimmunol.162.9.540710.4049/jimmunol.162.9.5407 ↗
19. 10.4049/jimmunol.177.5.288810.4049/jimmunol.177.5.2888 ↗
20. 10.1016/j.isci.2021.10313110.1016/j.isci.2021.103131 ↗
21. 10.1016/j.coi.2017.06.00510.1016/j.coi.2017.06.005 ↗
22. 10.1038/ncomms756510.1038/ncomms7565 ↗
23. 10.1126/scitranslmed.300062410.1126/scitranslmed.3000624 ↗
24. 10.1016/j.clim.2016.05.00710.1016/j.clim.2016.05.007 ↗
25. 10.1586/14760584.2014.86371510.1586/14760584.2014.863715 ↗
26. 10.15585/mmwr.mm6715a510.15585/mmwr.mm6715a5 ↗
27. 10.1038/nm98710.1038/nm987 ↗
28. 10.1111/cas.1282410.1111/cas.12824 ↗
29. 10.4049/jimmunol.181.5.299010.4049/jimmunol.181.5.2990 ↗
30. 10.1016/j.ymthe.2017.03.01310.1016/j.ymthe.2017.03.013 ↗
31. 10.1089/nat.2018.072110.1089/nat.2018.0721 ↗
32. 10.1016/j.jconrel.2011.07.02910.1016/j.jconrel.2011.07.029 ↗
33. 10.1016/j.vaccine.2019.05.06810.1016/j.vaccine.2019.05.068 ↗
34. 10.1016/j.vaccine.2015.10.13210.1016/j.vaccine.2015.10.132 ↗
35. 10.3390/vaccines803043310.3390/vaccines8030433 ↗
36. 10.3892/mmr.2022.1276910.3892/mmr.2022.12769 ↗
37. 10.1016/j.ijpharm.2020.12003310.1016/j.ijpharm.2020.120033 ↗
38. 10.1016/j.copbio.2021.09.01610.1016/j.copbio.2021.09.016 ↗
39. 10.1038/nature1297810.1038/nature12978 ↗
40. 10.1186/1465-9921-10-4310.1186/1465-9921-10-43 ↗
41. 10.4049/jimmunol.090320110.4049/jimmunol.0903201 ↗
42. 10.1038/3509956010.1038/35099560 ↗
43. 10.1016/j.jconrel.2006.04.01410.1016/j.jconrel.2006.04.014 ↗
44. 10.1016/j.ejpb.2023.08.00210.1016/j.ejpb.2023.08.002 ↗
45. 10.1016/j.jconrel.2018.08.02010.1016/j.jconrel.2018.08.020 ↗
46. 10.1007/s00018-015-1915-110.1007/s00018-015-1915-1 ↗
47. 10.1515/bmc-2018-000710.1515/bmc-2018-0007 ↗
48. 10.1016/S1369-5274(00)00199-510.1016/S1369-5274(00)00199-5 ↗
49. 10.4110/in.2018.18.e3310.4110/in.2018.18.e33 ↗
50. 10.1016/j.immuni.2021.11.00110.1016/j.immuni.2021.11.001 ↗
51. 10.1586/erv.11.1710.1586/erv.11.17 ↗
52. 10.1016/j.addr.2012.05.00910.1016/j.addr.2012.05.009 ↗
53. 10.1007/s00262-011-0970-110.1007/s00262-011-0970-1 ↗
54. 10.1080/0968786060079053710.1080/09687860600790537 ↗
55. 10.4049/jimmunol.180163410.4049/jimmunol.1801634 ↗
56. 10.1038/s41577-019-0143-610.1038/s41577-019-0143-6 ↗
57. 10.1038/s41573-019-0056-x10.1038/s41573-019-0056-x ↗
58. 10.1016/S1473-3099(11)70295-X10.1016/S1473-3099(11)70295-X ↗
59. 10.1016/j.coi.2018.03.02410.1016/j.coi.2018.03.024 ↗
60. 10.1038/nri.2017.10610.1038/nri.2017.106 ↗
61. 10.1038/nrd452910.1038/nrd4529 ↗
62. 10.1128/JVI.07172-1110.1128/JVI.07172-11 ↗
63. 10.1016/j.nano.2013.12.00310.1016/j.nano.2013.12.003 ↗
64. 10.1038/s41590-022-01160-y10.1038/s41590-022-01160-y ↗
65. 10.1186/s40425-019-0724-810.1186/s40425-019-0724-8 ↗
66. 10.1016/j.immuni.2016.10.01210.1016/j.immuni.2016.10.012 ↗
67. 10.1155/2012/83648510.1155/2012/836485 ↗
68. 10.1021/acs.jmedchem.9b0104410.1021/acs.jmedchem.9b01044 ↗
69. 10.1074/jbc.M90042920010.1074/jbc.M900429200 ↗
70. 10.3390/biology1102024610.3390/biology11020246 ↗
71. 10.1016/j.it.2016.10.00910.1016/j.it.2016.10.009 ↗
72. 10.1093/intimm/dxab07410.1093/intimm/dxab074 ↗
73. 10.1002/btm2.1028810.1002/btm2.10288 ↗
74. 10.1038/s41467-022-28417-210.1038/s41467-022-28417-2 ↗
75. 10.1146/annurev-immunol-030409-10121210.1146/annurev-immunol-030409-101212 ↗
76. 10.1038/nri100110.1038/nri1001 ↗
77. 10.1016/S0092-8674(04)00451-910.1016/S0092-8674(04)00451-9 ↗
78. 10.1038/ni1209x10.1038/ni1209x ↗
79. 10.1016/S1074-7613(03)00270-X10.1016/S1074-7613(03)00270-X ↗
80. 10.1016/j.imlet.2019.01.00310.1016/j.imlet.2019.01.003 ↗
81. 10.1084/jem.2006230510.1084/jem.20062305 ↗
82. 10.1084/jem.2007017610.1084/jem.20070176 ↗
83. 10.1016/j.jcis.2012.11.06110.1016/j.jcis.2012.11.061 ↗
84. 10.1586/erv.10.8910.1586/erv.10.89 ↗
85. 10.1021/acs.analchem.1c0042010.1021/acs.analchem.1c00420 ↗
86. 10.1016/S0264-410X(99)00526-510.1016/S0264-410X(99)00526-5 ↗
87. 10.1021/mp100208f10.1021/mp100208f ↗
88. 10.1038/s41467-024-44814-110.1038/s41467-024-44814-1 ↗
89. 10.1038/s41467-023-40015-410.1038/s41467-023-40015-4 ↗
90. 10.1021/acsnano.7b0174410.1021/acsnano.7b01744 ↗
91. 10.1056/NEJMoa202248310.1056/NEJMoa2022483 ↗
92. 10.1056/NEJMc203624210.1056/NEJMc2036242 ↗
93. 10.1016/j.ijpharm.2021.12058610.1016/j.ijpharm.2021.120586 ↗
94. 10.1016/j.addr.2022.11441610.1016/j.addr.2022.114416 ↗
95. 10.4049/jimmunol.120106510.4049/jimmunol.1201065 ↗