2. Academic Validation
  3. 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

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

  • ACS Nano. 2024 Jul 2;18(26):16589-16609. doi: 10.1021/acsnano.4c00278.
Atsushi Kawai 1 2 3,  Masahiro Noda 1 2 3,  Haruki Hirata 1 2 3,  Lisa Munakata 4,  Teppei Matsuda 1 2 3,  Daiki Omata 4,  Naoki Takemura 5,  Sakura Onoe 6,  Mika Hirose 6,  Takayuki Kato 6 7,  Tatsuya Saitoh 5 8 9,  Toshiro Hirai 1 2 3,  Ryo Suzuki 4,  Yasuo Yoshioka 1 2 3 7 8 9 10
Affiliations

Affiliations

  • 1 Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 2 Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 3 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.
  • 4 Laboratory of Drug and Gene Delivery Research, Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
  • 5 Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 6 Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 7 Center for Advanced Modalities and DDS, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 8 Center for Infectious Disease Education and Research, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 9 Global Center for Medical Engineering and Informatics, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 10 Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
PMID: 38885198 DOI: 10.1021/acsnano.4c00278
Abstract

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.

Keywords

Th1-type responses; adjuvant; influenza virus; interferon-γ; lipid nanoparticle; vaccine.

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