Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens

Hartikka, Jukka; Bozoukova, Vesselina; Ferrari, Marilyn E.; Sukhu, Loretta; Enas, J. D.; Sawdey, M.; Wloch, Mary K.; Tonsky, Katja; Norman, Jon; Manthorpe, Marston; Wheeler, Carl J.

doi:10.1016/s0264-410x(00)00445-x

Cited by 94 publications

(70 citation statements)

References 48 publications

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“…In brief, rabbits received 100 or 500 g of recombinant protein in complete Freund's adjuvant for first immunizations and half as much protein in five subsequent immunizations (incomplete Freund's adjuvant). For DNA immunization, rabbits were immunized intramuscularly six to 10 times by injection of 500 g of DNA with Vaxfectin adjuvant (DNA-to-vaxfectin molar ratio of 2:1) according to published methodologies (20).…”

Section: Methodsmentioning

confidence: 99%

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

et al. 2008

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Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size (ϳ350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines.

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Section: Methodsmentioning

confidence: 99%

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

et al. 2008

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“…They were also shown to stimulate humoral as well as cell-mediated immune responses and are therefore considered as potential adjuvants for protein-based or DNA-based vaccines [2][3][4][5][6][7]. In this context, we previously demonstrated that mice injected with diC14-amidine (3-tetradecylamino-tert-butyl-N-tetradecylpropionamidine) cationic liposomes combined with a recombinant allergen (Der p 1) developed a Th1-biased immune response and were protected against subsequent induction of a Th2-type allergen-specific response [8].…”

Section: Introductionmentioning

confidence: 99%

DiC14‐amidine cationic liposomes stimulate myeloid dendritic cells through Toll‐like receptor 4

et al. 2008

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DiC14-amidine cationic liposomes were recently shown to promote Th1 responses when mixed with allergen. To further define the mode of action of diC14-amidine as potential vaccine adjuvant, we characterized its effects on mouse and human myeloid dendritic cells (DC). First, we observed that, as compared with two other cationic liposomes, only diC14-amidine liposomes induced the production of IL-12p40 and TNF-a by mouse bone marrowderived DC. DiC14-amidine liposomes also activated human DC, as shown by synthesis of IL-12p40 and TNF-a, accumulation of IL-6, IFN-b and CXCL10 mRNA, and up-regulation of membrane expression of CD80 and CD86. DC stimulation by diC14-amidine liposomes was associated with activation of NF-jB, ERK1/2, JNK and p38 MAP kinases. Finally, we demonstrated in mouse and human cells that diC14-amidine liposomes use Toll-like receptor 4 to elicit both MyD88-dependent and Toll/IL-1R-containing adaptor inducing interferon IFN-b (TRIF)-dependent responses.

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“…Vaxfectin ® was initially tested as an adjuvant for enhancing humoral immune responses to plasmid DNA vaccines 27 and has subsequently been reported to enhance immune responses and/ or protection from pathogen challenge in a wide variety of animal models testing different plasmid DNA vaccines (reviewed in 28). Both lipids comprising Vaxfectin ® can be synthesized by straightforward, well-defined processes according to good manufacturing practices and Vaxfectin ® liposomes are easy to formulate with various forms of antigens.…”

Section: Discussionmentioning

confidence: 99%

“…23 In this report, a cationic lipid-based adjuvant, Vaxfectin ® , was formulated with seasonal and pandemic vaccines produced by Vero cell culture [24][25][26] and tested for adjuvanting immune responses. Vaxfectin ® is being developed for adjuvanting plasmid DNA vaccines 27,28 and has shown a promising safety profile in single radial immunodiffusion (SRD) assay. Interpretation of the SRD data was complicated by the fact that the staining pattern for Vaxfectin ® formulations yielded two concentric rings whereas intervals (CI) are shown (Fig.…”

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confidence: 99%

Preclinical evaluation of Vaxfectin^®-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines

Smith

Wodal

Crowe

et al. 2013

Human Vaccines & Immunotherapeutics

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Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens

Cited by 94 publications

References 48 publications

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

DiC14‐amidine cationic liposomes stimulate myeloid dendritic cells through Toll‐like receptor 4

Preclinical evaluation of Vaxfectin^®-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines

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Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens

Cited by 94 publications

References 48 publications

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

DiC14‐amidine cationic liposomes stimulate myeloid dendritic cells through Toll‐like receptor 4

Preclinical evaluation of Vaxfectin®-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines

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Preclinical evaluation of Vaxfectin^®-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines