The Effect of Cholesterol Content on the Adjuvant Activity of Nucleic-Acid-Free Lipid Nanoparticles
Jessica Anindita,
Hiroki Tanaka,
Takuma Yamakawa,
Yuka Sato,
Chika Matsumoto,
Kota Ishizaki,
Taiji Oyama,
Satoko Suzuki,
Keisuke Ueda,
Kenjirou Higashi,
Kunikazu Moribe,
Kasumi Sasaki,
Yumika Ogura,
Etsuo Yonemochi,
Yu Sakurai,
Hiroto Hatakeyama,
Hidetaka Akita
Affiliations
Jessica Anindita
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan
Hiroki Tanaka
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan
Takuma Yamakawa
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Yuka Sato
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Chika Matsumoto
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan
Kota Ishizaki
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Taiji Oyama
Sales Division, JASCO Corporation, 2967-5 Ishikawa, Hachioji City 192-8537, Tokyo, Japan
Satoko Suzuki
Applicative Solution Lab Division, JASCO Corporation, 2967-5 Ishikawa, Hachioji City 192-8537, Tokyo, Japan
Keisuke Ueda
Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Kenjirou Higashi
Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Kunikazu Moribe
Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Kasumi Sasaki
Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan
Yumika Ogura
Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan
Etsuo Yonemochi
Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan
Yu Sakurai
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan
Hiroto Hatakeyama
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan
Hidetaka Akita
Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan
RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.
