Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice

Sunay, Melek M.E.; Martins, Karen; Steffens, Jesse; Gregory, Melissa K.; Vantongeren, Sean A.; Hoeven, Neal Van; Garnes, Preston G.; Bavari, Sina

doi:10.1016/j.vaccine.2019.05.026

Cited by 17 publications

(12 citation statements)

References 45 publications

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“…Mice are a commonly used animal research model for investigating the regulatory and adjuvant functions of biologically active peptides in immune responses [14, 24, 25]. To evaluate the inducing effects on immune responses, in this paper, we primarily selected BALB/c female mice as the experimental animal model.…”

Section: Discussionmentioning

confidence: 99%

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

Feng

Zheng

Zong

et al. 2019

Vet Res

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The bursa of Fabricius (BF) is the acknowledged central humoural immune organ unique to birds and plays a vital role in B lymphocyte development. In addition, the unique molecular immune features of bursal-derived biological peptides involved in B cell development are rarely reported. In this paper, a novel bursal heptapeptide (BP7) with the sequence GGCDGAA was isolated from the BF and was shown to enhance the monoclonal antibody production of a hybridoma. A mouse immunization experiment showed that mice immunized with an AIV antigen and BP7 produced strong antibody responses and cell-mediated immune responses. Additionally, BP7 stimulated increased mRNA levels of sIgM in immature mouse WEHI-231 B cells. Gene microarray results confirmed that BP7 regulated 2465 differentially expressed genes in BP7-treated WEHI-231 cells and induced 13 signalling pathways and various immune-related functional processes. Furthermore, we found that BP7 stimulated WEHI-231 cell autophagy and AMPK-ULK1 phosphorylation and regulated Bcl-2 protein expression. Finally, chicken immunization showed that BP7 enhanced the potential antibody and cytokine responses to the AIV antigen. These results suggested that BP7 might be an active biological factor that functions as a potential immunopotentiator, which provided some novel insights into the molecular mechanisms of the effects of bursal peptides on immune functions and B cell differentiation.

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Section: Discussionmentioning

confidence: 99%

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

Feng

Zheng

Zong

et al. 2019

Vet Res

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that Ebola VLPs activate dendritic cells, induce neutralizing antibodies, and confer effective protection against lethal challenge of Ebola virus in animal models [ 19 , 20 , 21 , 23 , 34 , 49 , 50 ]. High-dose Ebola VLP vaccines have been shown to provide complete protection from Ebola virus infection in mouse and nonhuman primate models [ 19 , 21 , 23 ]; however, the addition of appropriate adjuvants would reduce the vaccine doses and elicit enhanced immune responses [ 51 , 52 ]. Ideal adjuvants would be safe in humans and effectively enhance vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Adjuvants for Ebola Virus-Like Particle Vaccine

et al. 2020

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Ebola virus disease is a severe disease, often fatal, with a mortality rate of up to 90%. Presently, effective treatment and safe prevention options for Ebola virus disease are not available. Therefore, there is an urgent need to develop control measures to prevent or limit future Ebola virus outbreaks. Ebola virus protein-based virus-like particle (VLP) and inactivated whole virion vaccines have demonstrated efficacy in animal models, and the addition of appropriate adjuvants may provide additional benefits to these vaccines, including enhanced immune responses. In this study, we screened 24 compounds from injectable excipients approved for human use in Japan and identified six compounds that significantly enhanced the humoral response to Ebola VLP vaccine in a murine model. Our novel adjuvant candidates for Ebola VLP vaccine have already been demonstrated to be safe when administered intramuscularly or subcutaneously, and therefore, they are closer to clinical trials than adjuvants whose safety profiles are unknown.

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“…The superior IgG titers of developed nanocarriers confirms its delivery effectiveness for venom immunogens, possibly increasing cell recognition or even cell uptake of these immunogens. Vaccine field may be benefitted of this type of nanocarriers adjuvants, as literature investigations demonstrated for immunogens and also nanocarrier association with immune agonists adjuvants to potentialize the effect associating two adjuvants mechanisms [ 14 , 15 , 16 ]. The PEI-covered nanoemulsions with superior IgG stimulant production showed that this biocompatible polymer capable of enhance cell uptake of nucleic acids and drugs [ 42 , 43 , 44 ] also may enhance protein cell recognition and be applied as vaccine adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…These systems potentially increase the adjuvant efficiency regarding to the expected immune response. Specifically, the nanoemulsions can induce a Th1 response due to the enhanced CpG agonist of toll like receptor (TLR) [ 14 ] and glucopyranosyl lipid [ 16 ], both agonists adjuvants that induces Th1 responses for influenza and Ebola vaccines, respectively. Particle-based adjuvants can induce the innate immunity activation through patterns receptor recognition (PRRs), which are receptors that recognize the secondary danger-associated signals.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against Tityus serrulatus Scorpion Venom

et al. 2020

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This study assesses the efficacy of different nanoemulsion formulations as new and innovative adjuvants for improving the in vivo immunization against the Tityus serrulatus scorpion venom. Nanoemulsions were designed testing key-variables such as surfactants, co-solvents, and the influence of the temperature, which would be able to induce the phase transition from a liquid crystal to a stable nanoemulsion, assessed for four months. Additionally, cationic-covered nanoemulsion with hyper-branched poly(ethyleneimine) was prepared and its performance was compared to the non-cationic ones. The physicochemical properties of the selected nanoemulsions and the interactions among their involved formulation compounds were carefully monitored. The cytotoxicity studies in murine macrophages (RAW 264.7) and red blood cells were used to compare different formulations. Moreover, the performance of the nanoemulsion systems as biocompatible adjuvants was evaluated using mice immunization protocol. The FTIR shifts and the zeta potential changes (from −18.3 ± 1.0 to + 8.4 ± 1.4) corroborated with the expected supramolecular anchoring of venom proteins on the surface of the nanoemulsion droplets. Cell culture assays demonstrated the non-toxicity of the formulations at concentrations less than 1.0 mg/mL, which were able to inhibit the hemolytic effect of the scorpion venom. The cationic-covered nanoemulsion has shown superior adjuvant activity, revealing the highest IgG titer in the immunized animals compared to both the non-cationic counterpart and the traditional aluminum adjuvant. In this approach, we demonstrate the incredible potential application of nanoemulsions as adjuvants, using a nanotechnology platform for antigen delivery system on immune cells. Additionally, the functionalization with hyper-branched poly(ethyleneimine) enhances this recognition and improves its action in immunization.

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Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice

Cited by 17 publications

References 45 publications

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells

Identification of Novel Adjuvants for Ebola Virus-Like Particle Vaccine

Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against Tityus serrulatus Scorpion Venom

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