Lipid Nanoparticles Potentiate CpG-Oligodeoxynucleotide-Based Vaccine for Influenza Virus

Shirai, Seiki; Shibuya, Meito; Kawai, Atsushi; Tamiya, Shigeyuki; Munakata, Lisa; Omata, Daiki; Suzuki, Ryo; Aoshi, Taiki; Yoshioka, Yasuo

doi:10.3389/fimmu.2019.03018

Cited by 30 publications

(37 citation statements)

References 58 publications

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“…The hydrodynamic diameter of the LNP was 86.5 nm (polydispersity index: 0.277), and the zeta potential of the LNP was 67.9 ± 12.1 mV. We had already confirmed the physical properties of LNP-CpG: The hydrodynamic diameter of LNP-CpG was 54.0 nm (polydispersity index: 0.157), and the zeta potential of LNP-CpG was 1.12 ± 8.26 mV [ 26 , 27 ].…”

Section: Resultsmentioning

confidence: 89%

“…We investigated the usefulness of the LNP as an adjuvant and compared the immune responses induced by the LNP, LNP-CpG, and alum. The LNP and LNP-CpG were prepared by using a microfluidic mixer system, NanoAssemblr, as described previously [ 26 , 27 ]. The hydrodynamic diameter of the LNP was 86.5 nm (polydispersity index: 0.277), and the zeta potential of the LNP was 67.9 ± 12.1 mV.…”

Section: Resultsmentioning

confidence: 99%

“…The prepared LNP was filtered through a 0.22-μm PVDF filter (Merck KGaA, Darmstadt, Germany). An LNP containing CpG ODN (LNP-CpG) was also prepared by using NanoAssemblr Benchtop, as described previously [ 26 , 27 ]. All LNP preparation work was performed at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…We have demonstrated the potential of the LNP we developed as a CpG ODN delivery vehicle [ 26 , 27 ]. We have already demonstrated that LNP containing CpG ODN (LNP-CpG) has stronger immune-activating activity in vitro and in vivo than CpG ODN [ 26 , 27 ]. In addition, LNP-CpG induces stronger antigen-specific antibody responses than CpG ODN in mice vaccinated with SV generated from influenza virus [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have already demonstrated that LNP containing CpG ODN (LNP-CpG) has stronger immune-activating activity in vitro and in vivo than CpG ODN [ 26 , 27 ]. In addition, LNP-CpG induces stronger antigen-specific antibody responses than CpG ODN in mice vaccinated with SV generated from influenza virus [ 27 ]. However, the usefulness of our LNP as an antigen-delivery vehicle remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2020

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Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue

Zhong,

Chen,

Deswarte

et al. 2023

Adv Healthcare Materials

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Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG‐ODNs) are short single‐stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9‐dependent NF‐κB signaling pathway. This feature is attractive to exploit in the context of vaccine design and cancer immunotherapy. Soluble CpG‐ODNs cause hepatic toxicity, which reduces its therapeutic applicability. The formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs) containing an ionizable cationic lipid that complexes CpG through electrostatic interaction is reported. Upon local administration, LNP‐formulated CpG drains to lymph nodes and triggers robust innate immune activation. Unformulated, soluble, CpG, by contrast, is unable to induce robust innate activation in draining lymph nodes and is distributed systemically. In a vaccination setting, LNP‐formulated CpG, admixed with a protein antigen, induces higher antigen‐specific antibody titers and T cell responses than antigen admixed with unformulated soluble CpG.

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Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

Dong

Wang

2021

Advanced NanoBiomed Research

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Influenza is one of the most severe and contagious respiratory infectious diseases. Influenza virus infection causes annual epidemics and occasional pandemics, resulting in an enormous health and economic burden worldwide. During the 2019-2020 flu season, the centers for disease control and prevention (CDC) estimates that flu caused 38 million illnesses, including 18 million medical visits, 405 000 hospitalizations, and 22 000 deaths in the United States. [1] Influenza viruses are enveloped RNA viruses of the Orthomyxoviridae family. Because the RNA polymerases lack the proofreading function, influenza viruses undergo constant antigenic drift and shift within animal and human reservoirs. [2] Influenza A viruses (IAVs) and influenza B viruses (IBVs) are the main circulating viruses that affect human health. So far, 18 hemagglutinin (HA) subtypes belonging to two HA phylogenetic groups and 11 neuraminidase (NA) subtypes have been identified for IAVs. [3] The IAVs H1N1 and H3N2 currently cause most epidemic diseases in humans. IBVs form a single antigenic group with two distinct lineages: Victoria and Yamagata.Seasonal vaccination is the most cost-effective method to combat influenza infection. However, current seasonal flu vaccines induce strain-specific immunity that rapidly wanes and displays low efficiencies against mismatched circulating strains and no effect on pandemics. The vaccines need annual reformulation based on the prediction by the WHO Global Influenza Surveillance and Response System to counter antigenic variations. [4] This uncertainty makes mismatches occur, resulting in suboptimal immunity. Fewer influenza cases occurred in the past 2020-2021 flu season in the United States than in any on record, [5] probably due to the widespread use of face masks and social distance to control COVID-19. The lack of exposure to the flu may make the population more susceptible to the virus when it returns. [6] Parallelly, predicting which strains will be circulating in the upcoming flu season and selecting vaccine manufacturing will be more challenging than ever.A next-generation universal influenza vaccine that elicits long-lasting cross-protective immunity against variant influenza strains will overcome the limitations of the current flu v accines. [7,8] Nanotechnology plays an indispensable role in the development of such vaccines. [9][10][11] Influenza viruses are nanosized particles enveloped by lipid membranes inserted with surface glycoprotein spikes. Nanoparticle vaccines can optimally mimic the influenza virus nanostructure with high antigen loads, facilitate targeted delivery and controlled antigen release, and synergize with molecular adjuvants to improve vaccine potency and breadth. Moreover, nanoparticle vaccines can facilitate rapid and scalable production, minimize cold-chain dependence, incorporate antigens in a flexibly modular fashion, and be affordably produced. Up to date, a variety of nanoparticle formulations have shown promising results in generating cross-reactive influenza immunity.

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Lipid Nanoparticles Potentiate CpG-Oligodeoxynucleotide-Based Vaccine for Influenza Virus

Cited by 30 publications

References 58 publications

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

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

Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

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