Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses

Lim, So-Yon; Meyer, Matt; Kjonaas, Richard A.; Ghosh, S.

doi:10.1186/1476-8518-4-6

Cited by 32 publications

(24 citation statements)

References 37 publications

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“…Phytol has already been used in cosmetics, household cleaners, detergents, and fragrance as an aromatic ingredient (McGinty, Letizia & Api, 2010). Interestingly, natural isoprenoid adjuvants, which is structurally similar to phytol, and phytol-derived compound PHIS-01 combined with the hapten, have been shown as the effective adjuvants on antibacterial immunity by increasing titers of IgG 2a antibody (Lim et al, 2006). …”

Section: Discussionmentioning

confidence: 99%

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

Cheng

Chen

Lin

et al. 2016

PeerJ

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BackgroundT cells play a pivotal role in the adaptive immunity that participates in a wide range of immune responses through a complicated cytokine network. Imbalance of T-cell responses is involved in several immune disorders. Neolitsea species, one of the biggest genera in the family Lauraceae, have been employed widely as folk medicines for a long time in Asia. Previous phytochemical investigations revealed the abundance of terpenes in the leaves of N. hiiranensis, an endemic Neolitsea in Taiwan, and demonstrated anti-inflammatory activities. However, the effect of N. hiiranensis on the functionality of immune cells, especially T cells, is still unclear. In this study, we utilize in vitro and in vivo approaches to characterize the effects of leaves of N. hiiranensis and its terpenoids on adaptive immune responses.MethodsDried leaves of N. hiiranensis were extracted three times with cold methanol to prepare crude extracts and to isolate its secondary metabolites. The ovalbumin (OVA)-sensitized BALB/c mice were administrated with N. hiiranensis extracts (5–20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects of N. hiiranensis on the production of OVA-specific antibodies and cytokines. To further identify the N. hiiranensis-derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated from N. hiiranensis by determining the cell viability, cytokine productions, and mRNA expression in the presence of OVA in vitro.ResultsCrude extracts of leaves of N. hiiranensis significantly inhibited IL-12, IFN-γ, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG2a in vivo. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves of N. hiiranensis suppressed IFN-γ in vitro. In addition, β-caryophyllene oxide attenuated the expression of IFN-γ, T-bet, and IL-12Rβ2 in a dose-dependent manner. N. hiiranensis-derived β-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γ production, and Th1-assocaited genes.ConclusionAs IFN-γ is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the N. hiiranensis and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.

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Section: Discussionmentioning

confidence: 99%

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

Cheng

Chen

Lin

et al. 2016

PeerJ

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“…After the publication of the study [1] we noticed a substantial error in our published article. In the original article [1] the dosage units were erroneously described in μg instead of mg. All references to μg quantities should be replaced with mg quantities throughout the manuscript.…”

Section: Introductionmentioning

confidence: 91%

“…In the original article [1] the dosage units were erroneously described in μg instead of mg. All references to μg quantities should be replaced with mg quantities throughout the manuscript. Also the LD50 should be g/kg instead of mg/kg.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Lim

Meyer

Kjonaas

et al. 2007

J Immune Based Ther Vaccines

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“…In an effort to address the issue, we focused on the phytol component of chlorophyll and studied different phytol derivatives for adjuvanticity [3,4]. Although phytol, a diterpenoid related to vitamin E, is known for many beneficial effects in animal studies, it could also be toxic as an adjuvant at high doses [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…An isoprenoid adjuvant, pristane, has been shown to promote lupus-like syndromes and pathologic nephritis in both autoimmune-prone and non-susceptible mouse strains after a single intra-peritoneal administration [9-11]. This is in contrast to the effects of isoprenoids phytol and its derivative PHIS-01[3]. Furthermore, squalene, a triterpene and Freunds' adjuvants (CFA/IFA) could also provoke lupus-like syndromes in non autoimmune- prone BALB/c mice [12].…”

Section: Introductionmentioning

confidence: 99%

Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

Aachoui

Ghosh

2011

BMC Immunol

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BackgroundVaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol) and PHIS-03 (phytanyl mannose), and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H), relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices.ResultsWe studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects.ConclusionAlthough all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in reducing the onset of autoimmune syndromes. However, SIS is least inflammatory among the adjuvants evaluated.

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Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses

Cited by 32 publications

References 37 publications

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

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Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

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