Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

Authors: S. Shirai, A. Kawai, M. Shibuya, L. Munakata, D. Omata, R. Suzuki and Y. Yoshioka

Journal: Vaccines

DOI: 10.3390/vaccines8030433

Publication - Abstract

August 03, 2020


In this in vitro and in vivo study, the Yoshioka lab at Osaka University investigated cytosine–phosphate–guanine oligodeoxynucleotides (CpG ODN) lipid nanoparticles (LNPs) as an adjuvant for seasonal split vaccines (SV) for the influenza virus. Earlier work by Shirai et. al. demonstrated that CpG ODN LNPs produce stronger immune-activating activity than CpG ODN alone.

The researchers found in this paper that split vaccines adjuvanted with LNPs produced better antigen-specific IgG1 and IgG2 responses, and that the Th1 response and does not induce inflammatory response with alum. Though the LNPs were able to induce SV-specific IgG1, IgG2b, IgG2c and Th1 responses, the LNPs did not enhance T-cell and antigen-specific antibody responses when rHA antigens were used. However, LNP-CpG/alum was found to improve T-cell and rHA-specific antibody responses. This difference could be due to difference in the adjuvant mechanism of LNPs and LNP-CpG/alum and requires further investigation. The LNPs were produced using NanoAssemblr technology.

This study showcases the ability of LNPs as an adjuvant and their potential to be utilized for improving efficacy and safety of influenza vaccines.


Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.

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