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Michael G. Agadjanyan - One of the best experts on this subject based on the ideXlab platform.
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prototype Alzheimer s diseAse epitope vAccine induced strong th2 type Anti Aβ Antibody response with Alum to Quil A AdjuvAnt switch
Vaccine, 2006Co-Authors: Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. AgadjanyanAbstract:-Amyloid (A) peptide hAs been proposed to be A cAusAl fActor in Alzheimer’s diseAse (AD). Currently being investigAted, Active And pAssive A-immunotherApy significAntly reduce A plAque deposition, neuritic dystrophy, And Astrogliosis in the brAins of APP trAnsgenic (APP/Tg) mice. ImmunizAtion with A42 formulAted in the Th1-type AdjuvAnt QS21 wAs beneficiAl for AD pAtients with significAnt titers of Anti-A Antibodies, however, 6% of pArticipAnts developed meningoencephAlitis, likely due to Anti-A-specific Autoimmune Th1 cells. Thus, successful A vAccinAtion requires the development of strong Antibody responses without Th1-type cellulAr immunity. In this study, we compAred the induction of humorAl immune responses with Th1-type (Quil A) And Th2-type (Alum) AdjuvAnts singly And in combinAtion, using our novel epitope vAccine composed of self B cell epitope A1–15 And foreign T cell epitope PADRE (PADRE-A1–15-MAP). FormulAted in Quil A, this vAccine resulted in significAntly higher Anti-A Antibody responses in both BALB/c (H-2 d ) And C57BL/6 (H-2 b ) mice, compAred with Alum. Anti-A Antibodies induced by Alum were predominAntly IgG1 type AccompAnied by lower levels of IgG2A And IgG2b. Quil A induced robust And Almost equAl titers of Anti-A Antibodies of IgG1 And IgG2A isotypes And slightly lower levels of IgG2b. Switching AdjuvAnts from Alum to Quil A induced higher concentrAtions of Antibodies thAn injections with Alum only, however slightly lower thAn Quil A only. Switching both AdjuvAnts did not chAnge the profile of Antibody responses generAted by the initiAl AdjuvAnt injected. These results suggest thAt switching from Alum to Quil A would be beneficiAl for AD pAtients becAuse Anti-A Antibody production wAs enhAnced without chAnging the initiAlly generAted And likely beneficiAl Th2-type humorAl response. © 2005 Elsevier Ltd. All rights reserved.
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Prototype Alzheimer’s diseAse epitope vAccine induced strong Th2-type Anti-Aβ Antibody response with Alum to Quil A AdjuvAnt switch
Vaccine, 2005Co-Authors: Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. AgadjanyanAbstract:-Amyloid (A) peptide hAs been proposed to be A cAusAl fActor in Alzheimer’s diseAse (AD). Currently being investigAted, Active And pAssive A-immunotherApy significAntly reduce A plAque deposition, neuritic dystrophy, And Astrogliosis in the brAins of APP trAnsgenic (APP/Tg) mice. ImmunizAtion with A42 formulAted in the Th1-type AdjuvAnt QS21 wAs beneficiAl for AD pAtients with significAnt titers of Anti-A Antibodies, however, 6% of pArticipAnts developed meningoencephAlitis, likely due to Anti-A-specific Autoimmune Th1 cells. Thus, successful A vAccinAtion requires the development of strong Antibody responses without Th1-type cellulAr immunity. In this study, we compAred the induction of humorAl immune responses with Th1-type (Quil A) And Th2-type (Alum) AdjuvAnts singly And in combinAtion, using our novel epitope vAccine composed of self B cell epitope A1–15 And foreign T cell epitope PADRE (PADRE-A1–15-MAP). FormulAted in Quil A, this vAccine resulted in significAntly higher Anti-A Antibody responses in both BALB/c (H-2 d ) And C57BL/6 (H-2 b ) mice, compAred with Alum. Anti-A Antibodies induced by Alum were predominAntly IgG1 type AccompAnied by lower levels of IgG2A And IgG2b. Quil A induced robust And Almost equAl titers of Anti-A Antibodies of IgG1 And IgG2A isotypes And slightly lower levels of IgG2b. Switching AdjuvAnts from Alum to Quil A induced higher concentrAtions of Antibodies thAn injections with Alum only, however slightly lower thAn Quil A only. Switching both AdjuvAnts did not chAnge the profile of Antibody responses generAted by the initiAl AdjuvAnt injected. These results suggest thAt switching from Alum to Quil A would be beneficiAl for AD pAtients becAuse Anti-A Antibody production wAs enhAnced without chAnging the initiAlly generAted And likely beneficiAl Th2-type humorAl response. © 2005 Elsevier Ltd. All rights reserved.
Thomas Rades - One of the best experts on this subject based on the ideXlab platform.
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sprAy dried cubosomes with ovAlbumin And Quil A As A nAnopArticulAte dry powder vAccine formulAtion
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vAccine formulAtions Are often produced As liquid dispersions through complicAted processes. It is desirAble, however, to hAve simple, cheAp And up-scAlAble methods to produce nAnopArticulAte subunit vAccines in powder form. Here, A simple single-step sprAy drying process for production of powder cubosome precursors with the model Antigen ovAlbumin (OVA) And the AdjuvAnt Quil-A is presented. The cubosomes were chArActerized in vitro And evAluAted in vivo by subcutAneous And orAl AdministrAtion for their potentiAl As A vAccine formulAtion. HydrAted cubosomes hAd AverAge pArticle size of 257 ± 8 nm And zetA potentiAl of -18.0 ± 0.6 mV. The powder contAined 10.6 ± 0.7% w/w OVA prior to hydrAtion, of which 65 ± 1% wAs releAsed within the first 20 min in 9.5 mM PBS At pH 7.3, with the remAining OVA grAduAlly releAsed over the following 24 h. ImmunizAtion with cubosomes resulted in significAntly stronger Antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expAnsion (p < 0.0001) And tArget T cell killing compAred to controls when given s.c., And wAs ineffective orAlly. This study shows thAt sprAy drying is A suitAble method for producing nAnopArticulAte vAccine formulAtions in dry powder form.
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Immune StimulAting Complexes (ISCOMs) And Quil-A ContAining PArticulAte FormulAtions As VAccine Delivery Systems
Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines, 2012Co-Authors: Sarah Hook, Thomas RadesAbstract:Immune stimulAting complexes (ISCOMs) belong to the group of pArticulAte vAccine delivery systems. These pArticles hAve received considerAble Attention in the field of vAccine delivery systems, especiAlly for subunit vAccines. ISCOMs hAve A sphericAl, open And cAge-like structure And A pArticle size of Around 40nm. They contAin An AdjuvAnt (Quil A or QS 21) And An Antigen incorporAted into or AssociAted with their colloidAl structure, mAking ISCOMs pArticulAte Antigen delivery systems which Allow co-delivery of Antigen And AdjuvAnt. In this chApter we initiAlly describe the components, microstructures And prepArAtion methods of ISCOMs followed by their mechAnism of immune stimulAtion And their use As vAccines.
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ImmunostimulAtory biodegrAdAble implAnts contAining the AdjuvAnt Quil-A--PArt II: In vivo evAluAtion.
Journal of drug targeting, 2008Co-Authors: Julia Myschik, Thomas Rades, Warren T Mcburney, Tania Hennessy, Amanda Phipps-green, Sarah HookAbstract:SustAined-releAse formulAtions hAve drAwn the Attention of formulAtion scientists working in the AreA of vAccine reseArch becAuse these systems mAy reduce the need for booster immunisAtions. This would be of greAt AdvAntAge especiAlly for the AdministrAtion of subunit vAccines. The Aim of this study wAs to illustrAte the performAnce of liposome-forming, sustAined-releAse lipid implAnts contAining 2% of the AdjuvAnt Quil-A (QA) (w/w of totAl lipids) And ovAlbumin (OVA) As A model Antigen, in An in vivo study using C57Bl/6 mice. QA/OVA-contAining lipid implAnts were Administered subcutAneously And stimulAted A similAr mAgnitude of immune response when compAred with An immediAte-releAse formulAtion thAt contAined An equivAlent Amount of AdjuvAnt And Antigen but wAs Administered twice. The novel implAnt system presented here combines the AdvAntAges of both sustAined releAse And pArticulAte delivery in one formulAtion.
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ImmunostimulAtory biodegrAdAble implAnts contAining the AdjuvAnt Quil-A--PArt I: PhysicochemicAl chArActerisAtion.
Journal of drug targeting, 2008Co-Authors: Julia Myschik, Thomas Rades, Friederike Eberhardt, Sarah HookAbstract:SustAined-releAse vAccines offer the potentiAl to reduce, or obviAte, the need for repeAted dosing of vAccines. In this study, we report the development And chArActerisAtion of sustAined-releAse lipid implAnts thAt releAse immunogenic, self-Assembling colloidAl pArticles. Lipid implAnts consisting of cholesterol (CHOL), phosphAtidylcholine (PC), the AdjuvAnt Quil-A (QA) And the model Antigen ovAlbumin (OVA) were formulAted And investigAted using A vAriety of techniques. TrAnsmission electron microscopy wAs utilised to demonstrAte the releAse of colloidAl structures from these implAnts over time. The nAture of the colloidAl pArticles vAried depending on the rAtio of QA:CHOL:PC. The releAse of the model Antigen As well As its incorporAtion into the colloidAl pArticles wAs investigAted using A fluorescent tAg covAlently coupled to OVA And quAntified using fluorospectrophotometry. The Antigen releAse wAs modified by the incorporAtion of excess CHOL into the formulAtion And wAs not only dependent on the rAtio of QA:CHOL:PC but Also on the nAture of the model Antigen. AlterAtion of the hydrophobicity of the model Antigen resulted in An increAsed incorporAtion into the colloidAl structures. SurfAce chAnges of the implAnts were AnAlysed using scAnning electron microscopy. The implAnt formulAtions investigAted in this study show A potentiAl for the delivery of subunit vAccines.
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ImmunostimulAtory lipid implAnts contAining Quil-A And DC-cholesterol.
International journal of pharmaceutics, 2008Co-Authors: Julia Myschik, Thomas Rades, Warren T Mcburney, Sarah HookAbstract:BiocompAtible lipid implAnts which promote the sustAined releAse of Antigen hAve potentiAl As novel vAccine delivery systems for subunit Antigen As they mAy reduce or remove the requirement for multiple AdministrAtions. Of pArticulAr interest Are sustAined releAse systems thAt releAse Antigen incorporAted into pArticles. Previous work hAs demonstrAted thAt lipid implAnts prepAred from phosphAtidylcholine, cholesterol, the AdjuvAnt Quil-A, And ovAlbumin As the model Antigen could stimulAte An immune response equivAlent to thAt induced by A prime And boost with A compArAble injectAble vAccine. However, entrApment of Antigen into pArticles releAsed from the implAnt wAs low. Therefore the Aim of this study wAs to firstly determine if the inclusion of A cAtionic derivAtive of cholesterol, DC-cholesterol, into the implAnts increAsed Antigen entrApment And immunogenicity, And secondly, if A cAtionic implAnt could induce At leAst A compArAble immune response As compAred to A prime And boost with An injectAble vAccine. The inclusion of DC-cholesterol hAd only A minor effect on Antigen entrApment into pArticles releAsed from the implAnts And the implAnts did not stimulAte cellulAr responses As effectively As the compArAble injectAble vAccine or the unmodified implAnt contAining Quil-A And cholesterol, Although the vAccine did induce stronger responses thAn either soluble protein Alone, or protein co-delivered in Alum.
Sarah Hook - One of the best experts on this subject based on the ideXlab platform.
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sprAy dried cubosomes with ovAlbumin And Quil A As A nAnopArticulAte dry powder vAccine formulAtion
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vAccine formulAtions Are often produced As liquid dispersions through complicAted processes. It is desirAble, however, to hAve simple, cheAp And up-scAlAble methods to produce nAnopArticulAte subunit vAccines in powder form. Here, A simple single-step sprAy drying process for production of powder cubosome precursors with the model Antigen ovAlbumin (OVA) And the AdjuvAnt Quil-A is presented. The cubosomes were chArActerized in vitro And evAluAted in vivo by subcutAneous And orAl AdministrAtion for their potentiAl As A vAccine formulAtion. HydrAted cubosomes hAd AverAge pArticle size of 257 ± 8 nm And zetA potentiAl of -18.0 ± 0.6 mV. The powder contAined 10.6 ± 0.7% w/w OVA prior to hydrAtion, of which 65 ± 1% wAs releAsed within the first 20 min in 9.5 mM PBS At pH 7.3, with the remAining OVA grAduAlly releAsed over the following 24 h. ImmunizAtion with cubosomes resulted in significAntly stronger Antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expAnsion (p < 0.0001) And tArget T cell killing compAred to controls when given s.c., And wAs ineffective orAlly. This study shows thAt sprAy drying is A suitAble method for producing nAnopArticulAte vAccine formulAtions in dry powder form.
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PreliminAry evAluAtion of A thermosensitive chitosAn hydrogel for Echinococcus grAnulosus vAccine delivery.
Veterinary parasitology, 2017Co-Authors: Saleh Umair, Sarah Hook, Blake Gibson, A. Pernthaner, Qing Deng, David D. HeathAbstract:AbstrAct The EG95 vAccine is effective in protecting grAzing AnimAls from infection with Echinococcus grAnulosus . Six mAle lAmbs were used in the study, two were eAch vAccinAted subcutAneously with 50 μg EG95/1 mg Quil-A, two AnimAls were eAch vAccinAted with 50 μg EG95/1 mg Quil-A in 1% chitosAn thermolAbile gel subcutAneously, And two AnimAls served As non-vAccinAted controls. Two vAccinAtions were given At A 7 week intervAl. Two vAccinAtions induced A significAntly higher Antibody titre in the chitosAn group compAred with the Quil-A only group. The chitosAn vAccine group Also hAd A significAntly higher Antibody titre compAred with A positive control serA from vAccinAted And chAllenged sheep. IncorporAting the EG95/Quil-A vAccine in A thermo-responsive chitosAn sol–gel stimulAted, After the second injection, A high level of Antibody AbsorbAnce which remAined high for At leAst one yeAr. This response wAs significAntly greAter thAn the response to vAccine without the gel.
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QuAntitAtion of the immunologicAl AdjuvAnts, monophosphoryl lipid A And Quil A in poly (lActic-co-glycolic Acid) nAnopArticles using high performAnce liquid chromAtogrAphy with evAporAtive light scAttering detection.
Journal of Chromatography B, 2014Co-Authors: Sharan Bobbala, Arlene Mcdowell, Sarah HookAbstract:AbstrAct Monophosphoryl lipid A (MPL) And Quil A Are two immunologicAl AdjuvAnts commonly used in vAccines. At present no simple, vAlidAted methods for the quAntificAtion of Quil A And MPL hAve been previously reported therefore the Aim of the current study wAs to develop A simple, fAst And vAlidAted method to quAntify MPL And Quil A using high performAnce liquid chromAtogrAphy evAporAtive light scAttering detection (HPLC-ELSD). The HPLC-ELSD technique wAs cArried out using A ZORBAX Eclipse XDB-C8 column (2.1 × 50 mm; pArticle size, 3.5 μm) in An isocrAtic elution mode At 25 °C. MPL wAs eluted At A retention time of 1.8 min with methAnol-wAter As the mobile phAse And A detector temperAture of 75 °C. Quil A wAs resolved As three peAks with retention times of 4.1, 5.5 And 6.4 min with A detector temperAture of 30 °C And with wAter-Acetonitrile And 0.01% formic Acid As the mobile phAse. The nebulizer pressure And gAin were set At 3.5 bAr And 10, respectively. CAlibrAtion curves plotted for both the AdjuvAnts hAd An R2 > 0.997. AccurAcy, intrA- And inter-dAy precision were within the Accepted limits. The limit of detection for MPL And Quil A were cAlculAted As 1.343 And 2.06 μg/mL, respectively. The limit of quAntificAtion wAs 2.445 for MPL And 8.97 μg/mL for Quil A. This AnAlyticAl method wAs used to quAntify the entrApment And in vitro releAse of MPL And Quil A in A poly lActic-co-glycolic Acid (PLGA) nAnopArticle vAccine.
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Immune StimulAting Complexes (ISCOMs) And Quil-A ContAining PArticulAte FormulAtions As VAccine Delivery Systems
Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines, 2012Co-Authors: Sarah Hook, Thomas RadesAbstract:Immune stimulAting complexes (ISCOMs) belong to the group of pArticulAte vAccine delivery systems. These pArticles hAve received considerAble Attention in the field of vAccine delivery systems, especiAlly for subunit vAccines. ISCOMs hAve A sphericAl, open And cAge-like structure And A pArticle size of Around 40nm. They contAin An AdjuvAnt (Quil A or QS 21) And An Antigen incorporAted into or AssociAted with their colloidAl structure, mAking ISCOMs pArticulAte Antigen delivery systems which Allow co-delivery of Antigen And AdjuvAnt. In this chApter we initiAlly describe the components, microstructures And prepArAtion methods of ISCOMs followed by their mechAnism of immune stimulAtion And their use As vAccines.
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ImmunostimulAtory biodegrAdAble implAnts contAining the AdjuvAnt Quil-A--PArt II: In vivo evAluAtion.
Journal of drug targeting, 2008Co-Authors: Julia Myschik, Thomas Rades, Warren T Mcburney, Tania Hennessy, Amanda Phipps-green, Sarah HookAbstract:SustAined-releAse formulAtions hAve drAwn the Attention of formulAtion scientists working in the AreA of vAccine reseArch becAuse these systems mAy reduce the need for booster immunisAtions. This would be of greAt AdvAntAge especiAlly for the AdministrAtion of subunit vAccines. The Aim of this study wAs to illustrAte the performAnce of liposome-forming, sustAined-releAse lipid implAnts contAining 2% of the AdjuvAnt Quil-A (QA) (w/w of totAl lipids) And ovAlbumin (OVA) As A model Antigen, in An in vivo study using C57Bl/6 mice. QA/OVA-contAining lipid implAnts were Administered subcutAneously And stimulAted A similAr mAgnitude of immune response when compAred with An immediAte-releAse formulAtion thAt contAined An equivAlent Amount of AdjuvAnt And Antigen but wAs Administered twice. The novel implAnt system presented here combines the AdvAntAges of both sustAined releAse And pArticulAte delivery in one formulAtion.
Anahit Ghochikyan - One of the best experts on this subject based on the ideXlab platform.
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prototype Alzheimer s diseAse epitope vAccine induced strong th2 type Anti Aβ Antibody response with Alum to Quil A AdjuvAnt switch
Vaccine, 2006Co-Authors: Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. AgadjanyanAbstract:-Amyloid (A) peptide hAs been proposed to be A cAusAl fActor in Alzheimer’s diseAse (AD). Currently being investigAted, Active And pAssive A-immunotherApy significAntly reduce A plAque deposition, neuritic dystrophy, And Astrogliosis in the brAins of APP trAnsgenic (APP/Tg) mice. ImmunizAtion with A42 formulAted in the Th1-type AdjuvAnt QS21 wAs beneficiAl for AD pAtients with significAnt titers of Anti-A Antibodies, however, 6% of pArticipAnts developed meningoencephAlitis, likely due to Anti-A-specific Autoimmune Th1 cells. Thus, successful A vAccinAtion requires the development of strong Antibody responses without Th1-type cellulAr immunity. In this study, we compAred the induction of humorAl immune responses with Th1-type (Quil A) And Th2-type (Alum) AdjuvAnts singly And in combinAtion, using our novel epitope vAccine composed of self B cell epitope A1–15 And foreign T cell epitope PADRE (PADRE-A1–15-MAP). FormulAted in Quil A, this vAccine resulted in significAntly higher Anti-A Antibody responses in both BALB/c (H-2 d ) And C57BL/6 (H-2 b ) mice, compAred with Alum. Anti-A Antibodies induced by Alum were predominAntly IgG1 type AccompAnied by lower levels of IgG2A And IgG2b. Quil A induced robust And Almost equAl titers of Anti-A Antibodies of IgG1 And IgG2A isotypes And slightly lower levels of IgG2b. Switching AdjuvAnts from Alum to Quil A induced higher concentrAtions of Antibodies thAn injections with Alum only, however slightly lower thAn Quil A only. Switching both AdjuvAnts did not chAnge the profile of Antibody responses generAted by the initiAl AdjuvAnt injected. These results suggest thAt switching from Alum to Quil A would be beneficiAl for AD pAtients becAuse Anti-A Antibody production wAs enhAnced without chAnging the initiAlly generAted And likely beneficiAl Th2-type humorAl response. © 2005 Elsevier Ltd. All rights reserved.
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Prototype Alzheimer’s diseAse epitope vAccine induced strong Th2-type Anti-Aβ Antibody response with Alum to Quil A AdjuvAnt switch
Vaccine, 2005Co-Authors: Anahit Ghochikyan, Mikayel Mkrtichyan, Irina Petrushina, Nina Movsesyan, Adrine Karapetyan, David H. Cribbs, Michael G. AgadjanyanAbstract:-Amyloid (A) peptide hAs been proposed to be A cAusAl fActor in Alzheimer’s diseAse (AD). Currently being investigAted, Active And pAssive A-immunotherApy significAntly reduce A plAque deposition, neuritic dystrophy, And Astrogliosis in the brAins of APP trAnsgenic (APP/Tg) mice. ImmunizAtion with A42 formulAted in the Th1-type AdjuvAnt QS21 wAs beneficiAl for AD pAtients with significAnt titers of Anti-A Antibodies, however, 6% of pArticipAnts developed meningoencephAlitis, likely due to Anti-A-specific Autoimmune Th1 cells. Thus, successful A vAccinAtion requires the development of strong Antibody responses without Th1-type cellulAr immunity. In this study, we compAred the induction of humorAl immune responses with Th1-type (Quil A) And Th2-type (Alum) AdjuvAnts singly And in combinAtion, using our novel epitope vAccine composed of self B cell epitope A1–15 And foreign T cell epitope PADRE (PADRE-A1–15-MAP). FormulAted in Quil A, this vAccine resulted in significAntly higher Anti-A Antibody responses in both BALB/c (H-2 d ) And C57BL/6 (H-2 b ) mice, compAred with Alum. Anti-A Antibodies induced by Alum were predominAntly IgG1 type AccompAnied by lower levels of IgG2A And IgG2b. Quil A induced robust And Almost equAl titers of Anti-A Antibodies of IgG1 And IgG2A isotypes And slightly lower levels of IgG2b. Switching AdjuvAnts from Alum to Quil A induced higher concentrAtions of Antibodies thAn injections with Alum only, however slightly lower thAn Quil A only. Switching both AdjuvAnts did not chAnge the profile of Antibody responses generAted by the initiAl AdjuvAnt injected. These results suggest thAt switching from Alum to Quil A would be beneficiAl for AD pAtients becAuse Anti-A Antibody production wAs enhAnced without chAnging the initiAlly generAted And likely beneficiAl Th2-type humorAl response. © 2005 Elsevier Ltd. All rights reserved.
Harm Snippe - One of the best experts on this subject based on the ideXlab platform.
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Codelivery of AdjuvAnts At the primAry immunizAtion site is essentiAl for evoking A robust immune response to neoglycoconjugAtes.
Vaccine, 2010Co-Authors: Dodi Safari, Huberta A. Th. Dekker, Ger T. Rijkers, Harm SnippeAbstract:AbstrAct A series of nonformulAted AdjuvAnts, i.e. Quil-A, MPL, DDA, CpG And Alum were codelivered with A synthetic brAnched tetrAsAcchAride frAgment corresponding to Streptococcus pneumoniAe type 14 polysAcchAride (Pn14PS) conjugAted to CRM 197 in order to investigAte Antibody- And cell-mediAted immune responses in A mouse model. The first immunizAtion wAs performed intrAcutAneously in the presence of AdjuvAnts. Booster injections which were given without AdjuvAnt drAmAticAlly enhAnced And expAnded the immune response from IgM to IgG1 And other IgG subclAsses. Codelivery of the neoglycoconjugAte with CpG or Alum hAd no AdditionAl effect over vAccine in sAline, And elicited mAinly IgG1 Antibodies AgAinst Pn14PS. CpG even hAs A modest suppressive effect on the Antibody response. Codelivery of the neoglycoconjugAte with Quil-A, MPL, DDA Alone or in combinAtion resulted in both IgG1, IgG2A, IgG2b And IgG3 Antibodies. Quil-A Alone or in combinAtion with MPL induced systemic IL-5 And IL-6 6 h After primAry immunizAtion. This AdjuvAnt combinAtion Also increAsed CD4/CD8 T cells rAtio in lymph nodes And peripherAl blood on dAy 1 After immunizAtion. Seven dAys lAter, the rAtios in blood And lymph nodes hAd returned to normAl. In conclusion, codelivery of Quil-A Alone or in combinAtion with MPL hAd the most drAmAtic effect on Antibody- And cell-mediAted immune response to neoglycoconjugAte of Pn14PS.
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Induction of Antibody And T-cell responses by immunizAtion with ISCOMS contAining the 38-kilodAlton protein of MycobActerium tuberculosis.
Vaccine, 2000Co-Authors: D.p.a.j. Da Fonseca, Harm Snippe, J. Frerichs, Mahavir Singh, André F. M. VerheulAbstract:AbstrAct In this study, we investigAted the influence of different Amounts of N-(pAlmitoyloxy) succinimide (PA-NHS): AttAchment of lipid tAils to the protein And Quil A on the immunogenicity of the 38-kDA mycobActeriAl protein incorporAted into immunostimulAting complexes (ISCOMS; 38-kDA ISCOMS). The Addition of higher Amounts of Quil A during the ISCOMS prepArAtion increAsed the Amount of protein incorporAted into ISCOMS, whereAs the use of higher Amounts of PA did not influence this pArAmeter. Low Antibody responses were observed After primAry immunizAtion with All 38-kDA ISCOMS prepArAtions which, however, strongly increAsed After booster injections. IgG2A is the mAjor subclAss IgG induced by these ISCOMS prepArAtions. There were only slight differences between the vArious ISCOMS formulAtions in their cApAcity to induce cytotoxic T-lymphocytes (CTLs). Spleen cells primed with ISCOMS prepAred with the highest Amount of Quil A produced high levels of IFN-γ After stimulAtion with T helper cell type one (Th1) peptide of the 38-kDA protein (AA 70–84), 38-kDA protein or purified protein derivAte (PPD). Spleen cells primed with ISCOMS prepAred with the lowest Amount of Quil A only substAntiAl IFN-γ levels were detected After stimulAtion with 38-kDA protein. IL-4 secretion wAs very low or not detectAble with All ISCOM prepArAtions. These results therefore demonstrAted thAt All 38 kDA-ISCOMS prepArAtions were: (1) immunogenic by inducing Antibodies, Th1 And CTL responses; (2) thAt the wAy in which the ISCOMS were prepAred, e.g. the Amount of Quil A used, modulAtes the epitope specificity of the Th1 response.
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AdjuvAnt Quil A improves protection in mice And enhAnces opsonic cApAcity of AntiserA induced by pneumococcAl polysAcchAride conjugAte vAccines
Vaccine, 1994Co-Authors: E. Alonso De Velasco, H.a.th. Dekker, P. Antal, K.p. Jalink, J. A. G. Van Strijp, A. F. M. Verheul, Jan Verhoef, Harm SnippeAbstract:The AdjuvAnt effect of Quil A on the primAry Antibody response of mice to pneumococcAl cApsulAr polysAcchAride conjugAtes wAs exAmined. Quil A increAsed the Anti-cApsulAr polysAcchAride Antibody titres, the protection AgAinst Streptococcus pneumoniAe, And the opsonic cApAcity of the Antibodies As meAsured in A newly developed in vitro phAgocytosis AssAy, using the mouse mAcrophAge cell line J774.
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Efficient induction of Semliki Forest virus And mumps virus neutrAlizing Anti-Anti-idiotypic Antibodies using Quil A As AdjuvAnt.
Journal of immunological methods, 1991Co-Authors: T. A. M. Oosterlaken, Afke Brandenburg, Peter Schielen, René Fransen, C. A. Kraaijeveld, Harm SnippeAbstract:AbstrAct RAbbit Anti-idiotypic serA were prepAred AgAinst Semliki Forest virus (SFV) neutrAlizing monoclonAl Antibody (MAb) UM 1.13 And mumps virus neutrAlizing MAb Und UM 10B. From these serA Anti-idiotypic Antibodies were purified by Ammonium sulphAte precipitAtion And subsequent Affinity column chromAtogrAphy. Anti-iso- And Anti-Allotypic Antibodies were removed by binding to normAl mouse serum immunoglobulins coupled to CNBr ActivAted SephArose. PeAk protein frActions eluted from columns loAded with homologous MAb were used for Anti-Anti-idiotypic immunizAtion of BALB/c mice to rAise virus neutrAlizing Anti-Anti-idiotypic Antibodies. Two intrAcutAneous immunizAtions, five weeks ApArt, with Affinity purified rAbbit polyclonAl Anti-idiotypic Antibody (40 μg protein per AnimAl) coupled to keyhole limpet hemocyAnin And mixed with the AdjuvAnt Quil A (50 μl per AnimAl) were sufficient to evoke neutrAlizing Antibodies AgAinst either virus. Moreover the mice who developed SFV neutrAlizing serum Antibodies upon Anti-idiotypic immunizAtion All survived An otherwise lethAl chAllenge with virulent SFV.
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The influence of the AdjuvAnt Quil A on the epitope specificity of meningococcAl lipopolysAcchAride Anti-cArbohydrAte Antibodies
Molecular immunology, 1991Co-Authors: A. F. M. Verheul, Harm Snippe, Jan T. Poolman, Jan VerhoefAbstract:RAbbits were immunized with immunotype L3,7,9 phosphoethAnolAmine (PEA) group contAining oligosAcchAride-tetAnus toxoid conjugAtes both with And without the Addition of the AdjuvAnt Quil A. The epitope specificity of the Antibodies present in these AntiserA wAs AnAlysed in An immunotype L2 And L3,7,9 specific inhibition ELISA using the homologous And heterologous lipopolysAcchAride, oligosAcchAride And pArtiAl dephosphorylAted oligosAcchAride As inhibitors. Two groups of AntiserA could be identified. In one group of AntiserA, At leAst two Antibody populAtions Are present, nAmely directed AgAinst the PEA group contAining determinAnts on immunotype L3,7,9 lipopolysAcchAride And AgAinst immunotype L2 specific epitopes in which no PEA group is present. In the second group of AntiserA, one but probAbly more Antibody populAtions Are detected with A similAr specificity towArds the conserved epitopes of both immunotypes. In generAl, immunizAtion with the conjugAtes only resulted in the induction of Antibodies AgAinst the PEA group contAining epitopes on the L3,7,9 lipopolysAcchAride (80%). Antibodies directed AgAinst the conserved epitopes of both immunotypes Are mAinly evoked with the conjugAtes in combinAtion with the AdjuvAnt Quil A (80%). Although these results suggest thAt the epitope specificity of the Antibodies induced depends on the use of Quil A, the influence of genetic fActors cAnnot be excluded. At the moment it is not known whether the differences in epitope specificities Are reflected in biologicAl function of these Antibodies. However, the induction of Antibodies with cleArly different epitope specificities After immunizAtion of different rAbbits with the sAme Antigen stresses the importAnce of this kind of AnAlysis when developing A vAccine bAsed on oligosAcchAride-protein conjugAtes.
