Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

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

doi:10.1186/1476-8518-4-5

Cited by 21 publications

(11 citation statements)

References 27 publications

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“…Escherichia coli were cultured in Luria Broth (LB) (Difco, Sparks, MD, USA) at 37°c for 14 h and harvested with phosphate buffer saline (PBS) (Bio Basic Inc., Ontario, Canada). Cells were washed in PBS by centrifugation at 500×g for 10 min at 4°c [ 53 ]. The concentration of E. coli was adjusted at 10 9 CFU/ml.…”

Section: Methodsmentioning

confidence: 99%

Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model

et al. 2016

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BackgroundEnteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5 years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes-causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole-cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes as a combined vaccine candidate.ResultsWe immunized Balb/C mice subcutaneously with 109 CFU of combined vaccine candidate and found a significant increase in survival rate post challenge compared to unimmunized controls (100 % survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6 weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNγ) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2 weeks after mice immunization compared to controls (p < 0.05). We also evaluated alum and cholera toxin B subunit (CTB) as potential adjuvant systems for our candidate vaccine. We found that CTB-adjuvanted combined vaccine candidate showed significantly higher IgG and IFNγ levels than alum.ConclusionsOverall, our combined vaccine candidate offered protection against the five main diarrheagenic E. coli pathotypes in a single vaccine using mouse model. To the best of our knowledge, this is the first combined vaccine against the five main diarrheagenic E. coli pathotypes that is cost-effective with promise for further testing in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-1891-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model

et al. 2016

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“…Bacteria were killed by heating suspensions to 60°C for 1 hr. [14]. The vaccine was tested for sterility before use according to OIE [15].…”

Section: Preparation Of E Coli Killed Vaccine For Immunizationmentioning

confidence: 99%

IMMUNIZATION OF MICE WITH KILLED E. coli K99 VACCINE FOR PROTECTION AGAINST COLIBACCILLOSIS

AA¹,

NM²,

NA³

2013

Int J of Micr Res

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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%

“…To develop safe and broadly effective immunostimulants from structurally diverse compounds, ranging from bacterial products and inorganic salts to biosynthetic intermediates and proteins, is a technical challenge [ 2 ]. 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%

“…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 ]. In earlier studies, we observed that modified phytol compounds such as PHIS-01 (Phytanol) and PHIS-03 (Phytanyl mannose) are safe and highly effective adjuvants in immunocompetent inbred strains of mice, BALB/c and C57BL/6 [ 3 , 4 , 7 , 8 ]. They enhance immunogenicity of many soluble protein antigens and also of heat-killed pathogens [ 3 , 4 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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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: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

Cited by 21 publications

References 27 publications

Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model

Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model

IMMUNIZATION OF MICE WITH KILLED E. coli K99 VACCINE FOR PROTECTION AGAINST COLIBACCILLOSIS

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

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