Effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rPA anthrax vaccine

Little, Stephen F.; Ivins, Bruce E.; Webster, W. Maurice; Norris, Sarah L.; Andrews, Gerard P.

doi:10.1016/j.vaccine.2006.12.043

Cited by 34 publications

(18 citation statements)

References 51 publications

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“…38). Moreover, it is apparent that the presence of adjuvant and formaldehyde in that vaccine contributes significantly to this response (39). Thus, it is conceivable that LeTx given in the absence of adjuvant may be used as a therapeutic agent within this time interval.…”

Section: Discussionmentioning

confidence: 99%

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Depeille¹,

Young²,

Boguslawski³

et al. 2007

Clinical Cancer Research

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Purpose: In this study, we tested the hypothesis that inhibition of mitogen-activated protein kinase kinases (MKK) inhibits tumor growth by acting on angiogenic signaling and by extension may form the basis of an effective strategy for treatment of Kaposi's sarcoma. Experimental Design: Murine endothelial cells expressing the human herpes virus 8 G protein–coupled receptor (vGPCR-SVEC) were treated with anthrax lethal toxin (LeTx). LeTx is a binary toxin ordinarily secreted by Bacillus anthracis and is composed of two proteins: protective antigen (the binding moiety) and lethal factor (the active moiety). Lethal factor is a protease that cleaves and inactivates MKKs. Results: In vitro, treatment of vGPCR-SVEC with LeTx inhibited MKK signaling, moderately inhibited cell proliferation, and blocked the ability of these cells to form colonies in soft agar. Treatment with LeTx also blocked the ability of these cells to release several angioproliferative cytokines, notably vascular endothelial growth factor (VEGF). In contrast, inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 with U0126 caused a substantial inhibition of proliferation but only modestly inhibited VEGF release. In xenograft models, i.v. injection of LeTx caused reduced tumor growth characterized immunohistochemically by inhibition of MKK signaling, decreased rates of proliferation, and reduced levels of VEGF and VEGF receptor 2, with a corresponding decrease in vascular density. Conclusions: These data support a role for MKK signaling in tumor growth and vascularization and are consistent with the hypothesis that inhibition of MKK signaling by LeTx or a similar agent may be an effective strategy for the treatment of Kaposi's sarcoma as well as other vascular tumors.

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Section: Discussionmentioning

confidence: 99%

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Depeille¹,

Young²,

Boguslawski³

et al. 2007

Clinical Cancer Research

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“…Generally, the Th2 effect is dependent on the amount and type of aluminum salts used in the formulation [29]. Differential effects have been seen between 500 and 158 µg of aluminum (Alhydrogel) with 25 µg of Bacillus anthracis recombinant protective antigen (rPA) in inducing neutralizing antibodies [36].…”

Section: Adjuvantation Mechanismsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…Exposure to these spores by cutaneous, gastrointestinal, or aerosol routes results in lethal anthrax infection [1]. Poly-D-glutamic acid capsule and anthrax toxin are the two factors that are related to the toxicity of B anthracis in living organism [2].…”

Section: Introductionmentioning

confidence: 99%

Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis

Chun

Choi

Cho

et al. 2012

Osong Public Health and Research Perspectives

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ObjectiveRecombinant protective antigen (rPA) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in Korea and the USA. By using the rPA produced from Bacillus brevis pNU212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.MethodsSerological responses of rPA anthrax vaccine were investigated in guinea pigs that were given single or two injections (interval of 4 weeks) of various amounts of rPA combined with aluminumhydroxide adjuvant. Guinea pigs were subsequently challenged by the intramuscular injection with 30 half-lethal doses (30LD50) of virulent Bacillus anthracis spores. Serumantibody titerswere determined by anti-PA IgGELISA and the ability of antibodies to neutralize the cytotoxicity of lethal toxin on J774A.1 cell was measured through the toxin neutralizing antibody (TNA) assay.ResultsTo examine correlations between survival rate and antibody titers, correlation between neutralizing antibody titers and the extent of protection was determined. Toxin neutralization titers of at least 1176 were sufficient to confer protection against a dose of 30LD50 of virulent anthrax spores of the H9401 strain. Such consistency in the correlation was not observed from those antibody titers determined by ELISA.ConclusionNeutralizing-antibody titers can be used as a surrogate marker.

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Effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rPA anthrax vaccine

Cited by 34 publications

References 51 publications

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Selection of Adjuvants for Enhanced Vaccine Potency

Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis

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