A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens

Swaminathan, Gokul; Thoryk, Elizabeth; Cox, Kara S.; Meschino, Steven; Dubey, Sheri; Vora, Kalpit A.; Celano, Robert; Gindy, Marian E.; Casimiro, Danilo R.; Bett, Andrew J.

doi:10.1016/j.vaccine.2015.10.132

Cited by 90 publications

(71 citation statements)

References 84 publications

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“…Emerging evidence suggests that nanoparticle-based immune-modulators have promising potential applications in the development of novel cancer vaccines and cancer directed immune-therapies [24]. We recently reported novel ionizable lipid nanoparticle formulations that—when combined with sub-unit vaccine antigens—did not require co-administration of immune agonists to generate strong B-cell and T-cell responses, including CD8+ T-cell responses [17]. However, the specific vaccination regimes required for the LNPs to boost antigen-specific responses were not thoroughly evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Lipid Nanoparticles were prepared at Merck (West Point, PA, USA) and characterized as previously described [17,20]. The LNPs are comprised of an ionizable amino lipid ((13Z,16Z)- N , N -dimethyl-3-nonyldocosa-13,16-dien-1-amine), distearoylphosphatidylcholine (DSPC), cholesterol, and poly(ethylene glycol)2000-dimyristoylglycerol (PEG2000-DMG), in a molar ratio of 58:30:10:2, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Then, using a sterile syringe, the specified volume of vaccination mixture was retrieved and administered to mice. Our group has recently published two papers where such detailed protocols are provided [17,22]. In addition, our group’s recent publication reported our characterization of antigen and adjuvant′s physio-chemical properties and stability [17].…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that co-administration of specific ionizable lipid nanoparticles (LNPs) with Hepatitis B surface antigen (HBsAg), and Ovalbumin (OVA) significantly enhances antigen-specific B-cell, CD4+ T-cell, and CD8+ T-cell responses in BALB/c (HBsAg) and C57BL/6 mice (OVA) [17]. While some reports have characterized the advantage of using nanoparticles to encapsulate/deliver antigens and TLR agonists such as PolyIC to induce strong antigen-specific CD8+ T cell responses [18,19], our LNPs do not require the encapsulation of TLR agonists or antigen to stimulate strong antigen-specific immune responses [17].…”

Section: Introductionmentioning

confidence: 99%

“…While some reports have characterized the advantage of using nanoparticles to encapsulate/deliver antigens and TLR agonists such as PolyIC to induce strong antigen-specific CD8+ T cell responses [18,19], our LNPs do not require the encapsulation of TLR agonists or antigen to stimulate strong antigen-specific immune responses [17]. However, the specific requirement for the co-administration of LNPs and antigen and the specific formulation characteristics that dictate the successful generation of strong antigen-specific immune responses by LNPs were not evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice

et al. 2016

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A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs) markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg) and Ovalbumin (OVA), respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h. We also evaluated formulations combining antigen, LNP, and aluminum-based adjuvant amorphous aluminum hydroxylphosphate sulfate (MAA) to look for synergistic adjuvant effects. Analyses of antigen-specific B-cell and T-cell responses from immunized mice revealed that the LNPs and antigens must be co-administered—both at the same time and in the same location—in order to boost antigen-specific immune responses. Mixing of antigen with MAA prior to formulation with LNP did not impact the generation of antigen-specific B-cell responses, but drastically reduced the ability of LNPs to boost antigen-specific T-cell responses. Overall, our data demonstrate that the administration of LNPs and vaccine antigen together enables their immune-stimulatory properties.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice

et al. 2016

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An Aggregation‐Induced Emission Molecule‐Assembled Nanovaccine with Self‐Adjuvanted Function for Cancer Immunotherapy

Zhang,

Wang,

Gao

et al. 2023

Adv Funct Materials

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Cancer nanovaccine is a promising therapeutic strategy; however, the complicated composition and ambiguous structure of cancer nanovaccines hinder their clinical application. Thus, developing minimalist nanovaccine with simple structural molecule and potent immunostimulatory function is with great value. Herein, an organic small molecule with well‐defined molecular structure and strong aggregation‐induced emission (AIE) activity is synthesized. This molecule can self‐assemble into nanoparticle (NM‐7) acting as not only adjuvant but also carrier to capture model antigen ovalbumin to form nanovaccine, which can effectively deliver and chronically release antigens and induce effective antigen cross‐presentation in draining lymph nodes. Additionally, the photophysical property of AIE molecule facilitates the determination of in vivo tissue distribution of NM‐7. Notably, NM‐7/ovalbumin (OVA) nanovaccine induces robust tumor‐specific CD8+ T‐cell responses with greatly reduced cell exhaustion. Accordingly, NM‐7/OVA nanovaccine shows potent efficacy in both prevention and therapeutic tumor models, and produces an impressive synergistic therapeutic effect when combined with immune checkpoint blockade (ICB) therapy. Therefore, AIE nanomaterial NM‐7 with simple synthesis, well‐defined molecular structure and self‐adjuvanted function provides a new reference and general strategy for cancer vaccine development.

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Determination of lipid content and stability in lipid nanoparticles using ultra high‐performance liquid chromatography in combination with a Corona Charged Aerosol Detector

Kinsey

Deiss

et al. 2021

Electrophoresis

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For many years, lipid nanoparticles (LNPs) have been used as delivery vehicles for various payloads (especially various oligonucleotides and mRNA), finding numerous applications in drug and vaccine development. LNP stability and bilayer fluidity are determined by the identities and the amounts of the various lipids employed in the formulation and LNP efficacy is determined in large part by the lipid composition which usually contains a cationic lipid, a PEG‐lipid conjugate, cholesterol, and a zwitterionic helper phospholipid. Analytical methods developed for LNP characterization must be able to determine not only the identity and content of each individual lipid component (i.e., the parent lipids), but also the associated impurities and degradants. In this work, we describe an efficient and sensitive reversed‐phase chromatographic method with charged aerosol detection (CAD) suitable for this purpose. Sample preparation diluent and mobile phase pH conditions are critical and have been optimized for the lipids of interest. This method was validated for its linearity, accuracy, precision, and specificity for lipid analysis to support process and formulation development for new drugs and vaccines. This article is protected by copyright. All rights reserved

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A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens

Cited by 90 publications

References 84 publications

Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice

Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice

An Aggregation‐Induced Emission Molecule‐Assembled Nanovaccine with Self‐Adjuvanted Function for Cancer Immunotherapy

Determination of lipid content and stability in lipid nanoparticles using ultra high‐performance liquid chromatography in combination with a Corona Charged Aerosol Detector

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