Induction of Th17 Cellular Immunity With a Novel Nanoemulsion Adjuvant

Bielinska, Anna U.; Gerber, Michele; Blanco, Luz P.; Makidon, Paul E.; Janczak, Katarzyna; Beer, Michael; Swanson, Benjamin J.; Baker, James R.

doi:10.1615/critrevimmunol.v30.i2.60

Cited by 51 publications

(53 citation statements)

References 46 publications

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“…This suggests that NE activates either CD80 or CD86 signaling, and CD80 activation alone is sufficient for the B cell-dependent IgG response but not for Th-1-type cell immunity. In addition to diminished Th-1-type responses, all investigated mutations severely repressed development of Th-17 immunity after immunization with NE adjuvant, as demonstrated in our previous study (27). In summary, we identified a unique set of signaling activities underlying the mechanism of the mucosal adjuvant W 80 5EC NE (Table II).…”

Section: Discussionsupporting

confidence: 71%

“…In contrast, the absence of TLR-MyD88 signaling has a profound effect on NE-induced cellular immunity. Our data also suggest that, in W 80 5EC NE-immunized mice, TLR2 and TLR4 differentially affect the Th-1/Th-2 balance, because TLR4 2/2 and MyD88 2/2 mice had severely diminished Th-1-and Th-17-type cytokine production and reduced IgG2b Ab titers, whereas Th-1 cytokines in TLR2-deficient mice were affected to a lesser degree (27). Furthermore, the absence of TLR2 and MyD88 resulted in the elevated expression of IL-5, IL-10, and IL-13 cytokines, despite functional TLR4.…”

Section: Discussionsupporting

confidence: 57%

“…These results demonstrate that W 80 5EC NE adjuvant does not require an IL-12 environment to elicit robust IgG responses. However, IL-12 and downstream signaling via the IL-12Rb1 receptor are necessary for activation and for maintenance of Th-1-balanced and Th-17-type cellular immunity (27).…”

Section: W 80 5ec Ne Induces Upregulation Of DC Maturation Markers Inmentioning

confidence: 99%

“…However, the significance of these findings to adjuvant activity remains open to debate (23)(24)(25)(26). Also, no TLR-based adjuvant appears to consistently produce a Th-17 response, which is now thought to be important in protecting mucosal surfaces during infection (27)(28)(29)(30). This suggests that activation of other mechanisms may be important, particularly on mucosal surfaces.…”

mentioning

confidence: 99%

“…We recently developed a mucosal nanoemulsion (NE) adjuvant, W 80 5EC, that does not contain known TLR or other innate receptor ligands but is able to enhance both humoral and cellular immunity (27,31,32). This NE adjuvant is simply an oil-in-water formulation of emulsified, highly refined soybean oil combined with nonionic and cationic surfactants and ethanol, and it is similar in size to many viruses that infect the nasal mucosa (32).…”

mentioning

confidence: 99%

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Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 57%

Section: W 80 5ec Ne Induces Upregulation Of DC Maturation Markers Inmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

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Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

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Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking

et al. 2012

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While the nasal mucosa is a potentially useful site for human immunization, toxin-based nasal adjuvants are generally unsafe and less effective in humans. Safe mucosal adjuvants that activate protective immunity via mucosal administration are highly dependent on barrier antigen sampling by epithelial and dendritic cells. Here, we demonstrate that protein antigens formulated in unique oil-in-water nanoemulsions results in unique trans-cellular antigen uptake in ciliated nasal epithelial cells, leading to delivery into nasal associated lymphoid tissue. Nanoemulsion formulation also enhances MHC class II expression in epithelial cells and DC activation/trafficking to regional lymphoid tissues in mice. These materials appear to induce local epithelial cell apoptosis and heterogeneous cytokine production by mucosal epithelial cells and mixed nasal tissues, including G-CSF, GM-CSF, IL-1a, IL-1b, IL-5, IL-6, IL-12, IP-10, KC, MIP-1a, TGF-β, and TSLP. This is the first observation of a nasal adjuvant that activates calreticulin-associated apoptosis of ciliated nasal epithelial cells to generate broad cytokine/chemokine responses in mucosal tissue.

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Induction of Th17 Cellular Immunity With a Novel Nanoemulsion Adjuvant

Cited by 51 publications

References 46 publications

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Vaccine adjuvants for infectious disease in the clinic

Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking

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