Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens

Wegmann, Frank; Gartlan, Kate H.; Harandi, Ali M.; Brinckmann, Sarah; Coccia, Margherita; Hillson, William R.; Kok, Wai Ling; Cole, Suzanne; Ho, Ling‐Pei; Lambe, Teresa; Puthia, Manoj; Svanborg, Catharina; Scherer, Erin M.; Krashias, George; Williams, Adam; Blattman, Joseph N.; Greenberg, Philip D.; Flavell, Richard A.; Moghaddam, Amin E.; Sheppard, Neil C.; Sattentau, Quentin J.

doi:10.1038/nbt.2344

Cited by 193 publications

(202 citation statements)

References 39 publications

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“…The results indicated that PEI could be used as a competent carrier for the delivery of a DNA vaccine. This idea was supported by Wegmann et al (27), who showed that PEI was a safe and efficient DNA vaccine adjuvant that induced a stronger immune response.…”

Section: Discussionsupporting

confidence: 61%

An enhanced immune response against G250, induced by a heterologous DNA prime-protein boost vaccination, using polyethyleneimine as a DNA vaccine adjuvant

Sun

Liu

Ruan

et al. 2014

Molecular Medicine Reports

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Abstract. The heterologous DNA prime-protein boost vaccination approach has been widely applied as an immune treatment for carcinoma. However, inefficient delivery of DNA remains a major issue. In the present study, polyethyleneimine (PEI) was used as a DNA vector carrier to improve the transfection efficiency of the DNA vaccine and stimulate the humoral and cellular immunity against the renal carcinoma-associated antigen G250. A protein vaccine was included in the immunization strategy in order to produce a prime-boost effect. A DNA plasmid encoding an antigen G250 fragment was constructed and complexed with PEI. A protein vaccine against G250 was expressed in BL21 (DE3) Escherichia coli cells, by transformation with a pET28a(+)/C-G250 plasmid. The protein was purified using a nickel-nitriloacetic acid purification system. The in vitro transfection efficiency of the DNA vaccine was analyzed in HEK293 human endothelial kidney cells. The in vitro transfection efficiency in HEK293 cells was highest 48 h after transfection. Furthermore, mice were primed with 200 µg pVAX1/C-250 plasmid complexed with PEI, and boosted using 50 µg of purified C-G250 protein.In order to evaluate the immune response the antibody titer, splenocyte response, and interferon-γ levels from CD8+ T-cell splenocytes were analyzed using ELISA, lymphocyte proliferation or enzyme-linked immunosorbent spot assays. Firstly, the pVAX1/C-G250 plasmid was shown to be constructed successfully. As compared with the DNA group, the antibody titer, lymphocyte proliferation percentage, and cytokine production level induced by the DNA-PEI and DNA-PEI+C-G250 groups were significantly higher. Furthermore, the DNA-PEI+C-G250 group exhibited the strongest humoral and cellular response. Owing to the adjuvant effect of PEI, the pVAX1/C-G250-PEI prime plus C-G250 protein boost regimen could induce a strong immune response, and has been proved to be a potent vaccine candidate against renal cell carcinoma.

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Section: Discussionsupporting

confidence: 61%

An enhanced immune response against G250, induced by a heterologous DNA prime-protein boost vaccination, using polyethyleneimine as a DNA vaccine adjuvant

Sun

Liu

Ruan

et al. 2014

Molecular Medicine Reports

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“…Herein branched PEI forms of 750 kD (B750) and 25 kD (B25) gave higher titers of antigen-specific mucosal IgA than linear PEI forms (L40 and L160). 65 Self-assembled cationic poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu) hybrid polypeptide micelles also showed high efficiency as a simple and potent vaccine delivery system, as OVA encapsulated in this cationic polypeptide micelle stimulated robust specific antibody production that was up to 70-90-fold greater than that generated using free OVA. These cationic polypeptide micelles were also capable of inducing immature DC (iDC) maturation, enhancing antigen presentation and promoting the formation of a germinal center.…”

Section: Passively Apc-targeting Nanocarriersmentioning

confidence: 99%

Applications of nanomaterials as vaccine adjuvants

Zhu

Wang

Nie³

2014

Human Vaccines & Immunotherapeutics

120

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Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigenspecific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

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“…In 2012, Wegmann et al [72] claimed that PEI is a potent mucosal adjuvant for human use and suggested that further investigation for improvement of potency and safety of PEI as an adjuvant suggests promising results. Many attempts to decrease the cytotoxicity of PEI by conjugation with other molecules have been varied out.…”

Section: Microscopymentioning

confidence: 99%