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

Abstract

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.

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

“…Besides, the developing strategy of vaccines has still studied for other diseases. Shirai et al demonstrated that LNPs could act as an adjuvant for influenza vaccines [ 162 ]. This was confirmed through the results about the immune-stimulatory effects on dendritic cells in mice and the protection ability of LNPs encapsulating the conventional seasonal split vaccine (SV) in comparison with bare SVs and SVs combined Alum.…”

“…Alum induced a high inflammatory response, which is considered a limitation of traditional adjuvants. In contrary, LNPs were able to induce SV-specific immune responses without inflammation [ 162 ]. Swaminathan et al also assessed the adjuvant activity of LNPs alone and of LNPs incorporating the synthetic TLR9 agonist, IMO-2125 adjuvant, in a mouse model [ 163 ].…”

State-of-the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2

“…Indeed, some NPs such as VLPs, lipid NPs, and Au NPs may serve as costimulatory (adjuvant) agents. 146 − 148 Also, polymeric or self-assembling protein NPs could encapsulate and preserve antigens against early biodegradation and elimination. 24 , 149 Moreover, NPs would be targeted toward the immune cells for enhanced responses.…”

Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery

“…[47]. Excessive immune reaction to LNPs is not desirable because uncontrolled cytokine release can lead to life-threating conditions; however, carefully designed im-mune response activation can be used as an adjuvant in RNA-LNP-based vaccines [48,49]. Though using cationic lipids has disadvantages, as detailed above, the positive charge very efficiently entraps nucleic acids.…”