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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 Nanoparticles Containing a Specific Lipid Boost Th1 Cell and Antibody Responses to a Vaccine
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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 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 (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. 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. Streptococcus pneumoniae
Key numbers
60×
Increase in IFN-γ Production
IFN-γ levels in mice vaccinated with plus vs. plus CpG ODNs.
4 of 5
Total IgG Response Increase
Mice vaccinated with plus showed higher -specific total IgG compared to alone.