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

• Published in: ACS nano 2024-07, Vol.18 (26), p.16589-16609
• Main Authors: Kawai, Atsushi, Noda, Masahiro, Hirata, Haruki, Munakata, Lisa, Matsuda, Teppei, Omata, Daiki, Takemura, Naoki, Onoe, Sakura, Hirose, Mika, Kato, Takayuki, Saitoh, Tatsuya, Hirai, Toshiro, Suzuki, Ryo, Yoshioka, Yasuo
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacology; Adjuvants, Vaccine - chemistry; Adjuvants, Vaccine - pharmacology; Animals; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - chemistry; COVID-19 Vaccines - immunology; Female; Influenza Vaccines - chemistry; Influenza Vaccines - immunology; Lipids - chemistry; Liposomes; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology; Th1 Cells - drug effects; Th1 Cells - immunology
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/acsnano.4c00278

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.