scholarly journals Incomplete Freund’s adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment

2020 ◽  
Vol 8 (1) ◽  
pp. e000544
Author(s):  
Karlyn E Pollack ◽  
Max O Meneveau ◽  
Marit M Melssen ◽  
Kevin T Lynch ◽  
Alexander F Koeppel ◽  
...  
Keyword(s):  
Normal Skin ◽  
Adaptor Proteins ◽  
Skin Microbiome ◽  
Link Type ◽  
Arginase 1 ◽  
Vaccine Site ◽  
Enhanced Expression ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

BackgroundImmunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME.MethodsBiopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq.ResultsVSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p<0.01), CD40 and CD40L (p<0.0001) over normal skin; these effects were significantly enhanced for SSV with peptides+IFA. Vaccines containing pICLC increased expression of TBX21 (T-bet) but did not decrease GATA3 over normal skin, whereas SSV with peptides in IFA dramatically enhanced TBX21 and decreased GATA3, with high expression of IFNγ and STAT1. SSV with peptides in IFA also reduced arginase-1 (ARG1) expression and enhanced expression of TLR adapter molecules TICAM-1 (TRIF) and MYD88. Furthermore, SSV with IFA and peptides also enhanced expression of chemokines associated with TLS formation.ConclusionsThese findings suggest that SSV with peptides in IFA enhances CD40L expression by CD4 T cells, supports a Th1 microenvironment, with accumulation of activated and mature DC. Increased expression of TLR adaptor proteins after SSV with peptides in IFA might implicate effects of the skin microbiome. Reduced ARG1 may reflect diminished suppressive myeloid activity in the VSME.Trial registration number(NCT00705640,NCT01585350).

scholarly journals SPECIFICITY OF ANTIBODY BOVINE ZONNA PELLUCIDAE 3 (ANTI-bZP3) TO RABBIT ZP3 BASED ON bZP3 AS CONTRACEPTIVE ANTIGENS

2010 ◽  
Vol 5 (2) ◽  
pp. 182-187
Author(s):  
Edwin Widodo ◽  
Aulanni’am Aulanni’am
Keyword(s):  
Rabbit Serum ◽  
Elisa Method ◽  
Purple Colour ◽  
Control Female ◽  
Fertilization Process ◽  
Female Rabbit ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Dot Blotting

Zonna pellucidae can be develop as antigen potential candidates based on reversible immunocontraceptive vaccines. Immunogenic sites of bovine zonna pellucidae 3 (bZP3) could stimulated the presence of anti-bZP3 which be located on rabbit ZP and inhibit sperm-egg interaction on fertilization process. Purpose of this research is to detect spesific binding anti-bZP3 to rabbit oocytes using dot blotting and ELISA method. Sub cutan induction of bZP3 with Freund's adjuvant, CFA (Complete Freund's Adjuvant) for initial immunization and following by IFA (Incomplete Freund's Adjuvant) at the 14th day and 39th day. Control female rabbit injected by Tris-Cl buffer diluted in Freund's adjuvant without bZP3 antigen. Rabbit serum injected to rat for producing Rat Anti Rabbit Anti-bZP3. This research concludes spesific binding of anti-bZP3 with increasing purple colour on dot blotting methods. Anti-bZP3 increasing on 24th day and 31th day and still until 48th day. Measurement with ELISA methods showed increased titer on OD405. Highest titer showed on 31th day post immunization. Anti-bZP3 synthetized by bZP3 induced on rabbit detectable by immunohistochemistry methods on late primary oocytes, early secondary oocytes, growing secondary oocytes, and oocytes on de Graaf folicular phase. Keywords: Dot blotting, ELISA, bZP3, anti-bZP3

scholarly journals Autoimmunity to type II collagen an experimental model of arthritis.

1977 ◽  
Vol 146 (3) ◽  
pp. 857-868 ◽  
Author(s):  
D E Trentham ◽  
A S Townes ◽  
A H Kang
Keyword(s):  
Type Ii Collagen ◽  
Intradermal Injection ◽  
Type I ◽  
Type Ii ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Cartilage Proteoglycans ◽  
Bacterial Preparations ◽  
Helical Region

We have found that intradermal injection of native type II collagen extracted from human, chick or rat cartilage induces an inflammatory arthritis in approximately 40% of rats of several strains whether complete Freund's adjuvant or incomplete Freund's adjuvant is used. Type I or III collagen extracted from skin, cartilage proteoglycans and alpha1(II) chains were incapable of eliciting arthritis, as was type II collagen injected without adjuvant. The disease is a chronic proliferative synovitis, resembling adjuvant arthritis in rats and rheumatoid arthritis in humans. Native type II co-lagen modified by limited pepsin digestion still produces arthritis, suggesting that type-specific determinants residing in the helical region of the molecule are responsible for the induction of disease. Since homologous type II collagen emulsified in oil without bacterial preparations regularly causes the disease, this new animal model of arthritis represents a unique example of experimentally-inducible autoimmunity to a tissue component.

scholarly journals CD8+ CTL Priming by Exact Peptide Epitopes in Incomplete Freund’s Adjuvant Induces a Vanishing CTL Response, whereas Long Peptides Induce Sustained CTL Reactivity

2007 ◽  
Vol 179 (8) ◽  
pp. 5033-5040 ◽  
Author(s):  
Martijn S. Bijker ◽  
Susan J. F. van den Eeden ◽  
Kees L. Franken ◽  
Cornelis J. M. Melief ◽  
Rienk Offringa ◽  
...  
Keyword(s):  
Ctl Response ◽  
Peptide Epitopes ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Immunotolerance to Insulin and Freund's Adjuvant

1971 ◽  
Vol 49 (8) ◽  
pp. 865-866 ◽  
Author(s):  
P. J. Moloney ◽  
M. A. Evans
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Antibody Formation ◽  
Essential Factor ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant ◽  
Induction Of Tolerance

Prior injections of incomplete Freund's Adjuvant with saline did not suppress antibody formation by ox insulin. This finding is in contrast to that of Jankovic (Colloq. Int. Cent. Nat. Rech. Sci. 116, 187 (1963)), namely that prior injection of complete Freund's Adjuvant suppressed antibody formation to bovine serum albumin. The essential factor in the induction of tolerance to insulin by injection of maleyl insulin in incomplete Freund's Adjuvant is maleyl insulin.

scholarly journals Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity

2006 ◽  
Vol 203 (4) ◽  
pp. 851-856 ◽  
Author(s):  
Rafael S. Grajewski ◽  
Phyllis B. Silver ◽  
Rajeev K. Agarwal ◽  
Shao-Bo Su ◽  
Chi-Chao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Activity ◽  
Effector T Cells ◽  
Cell Repertoire ◽  
Immunological Responses ◽  
Endogenous Expression ◽  
Specific Effector ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Susceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by “natural” CD4+CD25+ regulatory T (T reg) cells. To examine whether endogenous expression of IRBP is necessary to generate these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a uveitogenic regimen of IRBP in complete Freund's adjuvant (CFA) exhibited CD25+ regulatory cells that could be depleted by PC61 treatment, which suppressed development of uveitogenic effector T cells and decreased immunological responses to IRBP. These EAU-relevant T reg cells were not IRBP specific, as their activity was not present in IRBP KO mice immunized with IRBP in incomplete Freund's adjuvant (IFA), lacking mycobacteria (whereas the same mice exhibited normal T reg cell activity to retinal arrestin in IFA). We propose that mycobacterial components in CFA activate T reg cells of other specificities to inhibit generation of IRBP-specific effector T cells in a bystander fashion, indicating that effective T reg cells can be antigen nonspecific. Our data also provide the first evidence that generation of specific T reg cells to a native autoantigen in a mouse with a diverse T cell repertoire requires a cognate interaction.

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