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PubMed1988

Enhancement of peptide immunogenicity by linear polymerization.

The effect of linear homopolymerization on the immunogenicity of synthetic peptides was studied using either haptenic peptides (representing amino acid sequences 103-115 and 133-147 of bovine rotavirus major protein) or immunogenic peptides TD-103-115 and TD-133-147 which were constructed by co-linear synthesis of the former peptides and an amino acid sequence representing a determinant recognized by T helper cells (TD). It was found that the two haptenic peptides were rendered immunogenic by linear homopolymerization. Moreover, homopolymerization also enhanced the immunogenicity of TD-103-115 but not that of TD-133-147. In the three cases where polymerization enhanced immunogenicity, a reinforced amphipathic pattern was predicted in the neighborhood of the junction of the monomers. The possibility that polymerization might have generated a new T cell determinant is discussed.

Amino Acid Sequence↗
PubMed1984

The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells.

Two clones of the 3LL Lewis lung carcinoma, a low-metastatic clone A9 and a high-metastatic clone D122, were studied for MHC expression and immunogenic properties. Using monoclonal antibodies, we demonstrated that the A9 clone expresses both the H-2Kb and the H-2Db, whereas the D122 expresses only the H-2Db, and lacks the expression of the H-2Kb encoded molecules. Cells of the low-metastatic clone A9 grew progressively in syngeneic (C57BL/6J) or in F1 mice, but were rejected in allogeneic recipients. The high-metastatic D122 grew progressively in all mouse strains tested, yet metastases were formed only in syngeneic recipients. When H-2 recombinant mice were used, the A9 again manifested a significantly greater immunogenic potency than the metastatic D122, which grew in all 4 recombinants tested. Metastases, however, were formed in B10HTG and to a lesser extent in B10A(4R), thus indicating that metastasis formation is restricted by both C57BL background and H-2Db sub region. We subsequently tested whether the higher immunogenicity of the H-2Kb-positive A9 cells is expressed also in syngeneic mice, to examine whether this could account for its low metastatic phenotype. We found that immunization by A9 cells significantly inhibited the growth of a subsequent A9 graft and even of D122, yet D122 did not retard the growth of secondary D122 or A9 cells. The increased immunogenic effect was expressed also in the generation of syngeneic cytotoxic lymphocytes by A9 but not by D122 cells. We suggest that expression of H-2K molecules on the 3LL clones, immunogenicity and the metastatic phenotype are causally related in this system.

Animals↗
PubMed1999

Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine.

A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines.

Animals↗
PubMed1998

The effect of low-profile serine substitutions in the V3 loop of HIV-1 gp120 IIIB/LAI on the immunogenicity of the envelope protein.

Many microbial antigens contain powerful hypervariable epitopes that fail to induce broadly protective immunity because they dominate the immune response at the expense of more conserved but weaker epitopes. If the undesired B cell epitopes are eliminated, the immune system could be focused on the conserved epitopes and produce a stronger antibody response to conserved parts of the protein and thus become a more efficacious immunogen for a vaccine. We examined this possibility using the human immunodeficiency virus envelope glycoprotein (gp)120 IIIB/LAI and selectively replaced the amino acids from the V3 region and analyzed the overall immunogenicity of the mutant proteins after nucleic acid immunization in mice. The most variable residues of the human immunodeficiency virus type 1 gp120 V3 loop sequence were replaced with serine, which has a small uncharged hydrophilic side chain and therefore is likely to be less immunogenic than amino acids found in wildtype V3 sequences. The serine substitutions did not affect the ability of soluble CD4 to bind the mutant molecules compared with wildtype gp120 and monoclonal antibodies against both linear and discontinuous epitopes located in the V1/V2, C1, and C4 regions of the molecule. These data suggest that the V3 loop substitutions did not grossly affect the overall conformation of the envelope molecule. Immunization of CBA x BALB/c F1 mice with DNA expression plasmids for the wild-type gp120 sequence induced a predominantly IgGI antibody response with end point titers of 10(4)-5 x 10(4). The antibodies reacted only with conformationally intact gp120. Serine replacements targeted to both sides of the V3 loop had a major impact on gp120 immunogenicity, with a markedly reduced response in the majority of animals tested. Analysis of the epitope specificity of the responses suggests that N-terminal amino acids in the V3 loop contribute to the major immunodominant epitope and provides no evidence that their removal enhances immunogenicity of the conserved regions.

AIDS Vaccines↗
PubMed1992

O6-methylguanine-DNA methyltransferase activity and induction of novel immunogenicity in murine tumor cells treated with methylating agents.

To investigate the mechanism of the generation of immunogenic tumor variants by mutagenic drugs, murine leukemia cells exhibiting different sensitivity to killing by the alkylator 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and different ability to repair O6-methyl-guanine in their DNA were treated in vitro with a series of methylating agents, including triazene derivatives, temozolomide, and streptozotocin. At the population level, we found that BCNU-resistant cells (L1210/BCNU) that appeared to be cross-resistant to killing by a dimethyltriazene and expressed high levels of O6-methylguanine-DNA methyltransferase activity (mer+ phenotype) failed to generate highly immunogenic variant sublines on repeated exposure to the methylating agents. In contrast, all cells (L1210) that were susceptible to DNA alkylation damage and deficient in O6-methylguanine repair (mer-) developed immunogenic variant sublines. A noticeable exception was represented by streptozotocin treatment, which was equally effective in mer+ and mer- cells. At the clonal level, a single exposure to streptozotocin or a triazene derivative resulted in a high incidence (33% and 50%, respectively) of immunogenic cell generation in mer- cells only. In mer+ cells, streptozotocin treatment led to a 33% incidence of immunogenic clones only when the cells were concurrently exposed to O6-methylguanine as a free base. The activity of O6-methylguanine-DNA methyltransferase in mer+ cells was greatly reduced by treatment with O6-methylguanine or streptozotocin, and the combination of the two drugs led to enzyme levels similar to those observed in mer- cells. Taken together, these data suggest that the mechanism of O6-alkylation may be operative in the induction of novel tumor-cell antigenicity by methylating agents.

Alkylating Agents↗
PubMed1996

Viral load, CD4 percentage, and delayed-type hypersensitivity in subjects receiving the HIV-1 immunogen and antiviral drug therapy.

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2-5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.

AIDS Vaccines↗
PubMed1993

The immunogenic properties of drug-resistant murine tumor cells do not correlate with expression of the MDR phenotype.

Alterations in the immunogenic properties of tumor cells frequently accompany selection for multiple-drug-resistant (MDR) variants. Therefore, studies were performed to examine the hypothesis that overexpression of membrane P-glycoprotein, commonly observed in MDR tumor cells, is associated with enhanced immunogenic properties. Immunogenicity was determined by (a) the ability of drug-sensitive parental UV2237M fibrosarcoma cells and drug-resistant UV2237M variant cells to immunize normal mice against rechallenge with parental tumor cells and (b) the ability of normal syngeneic mice to reject cell inocula that caused progressive tumor growth in immunocompromised mice. Variant UV2237M cell lines included subpopulations selected for a six- to ten-fold increase in mRNA for P-glycoprotein and expression of the MDR phenotype (resistance to doxorubicin) and cells sensitive to doxorubicin (and no expression of MDR properties) but resistant to ouabain. All UV2237M drug-resistant cells were highly immunogenic in immunocompetent mice, regardless of their MDR phenotype. Additional studies showed that CT-26 murine adenocarcinoma cells, sensitive or resistant to doxorubicin (expressing high levels of P-glycoprotein), injected into normal syngeneic Balb/c mice produced rapidly growing tumors. The data do not demonstrate a correlation between the immunogenic properties of drug-resistant tumor cells and the expression of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Cancer immunogene therapy: a review.

Although immunotherapy has long held out promise as a specific, potent approach to cancer therapy, clinical applications have been unrewarding to date. However, advances in gene transfer technology and basic immunology have opened new avenues to stimulate antitumor immune responses including immunogene therapy. Many different approaches to immunogene therapy have been identified. These include transferring genes encoding proinflammatory proteins to tumor cells, suppressing immunosuppressive gene expression, and transferring proinflammatory genes and/or tumor antigen genes to professional antigen-presenting cells. In some cases, genes are transferred to tumor or antigen-presenting cells in situ. In others, gene transfer is performed ex vivo as part of preparing an anticancer vaccine. We discuss the underlying approach, relative success, and clinical application of various cancer immunogene therapy strategies, paying particular attention to immunogene therapy vaccines. Large numbers of preclinical studies have been reported, but only scattered clinical trial results have appeared in the literature. Although very successful preclinically, the ideal cancer immunogene therapy approach remains to be determined and will likely vary with tumor type. Clinical impact may be improved in the future as treatment protocols are refined.

Genetic Therapy↗
PubMed1997

Effect of pH and temperature on the immunogenicity of glycinin (Glycine max L.).

Sensitive immunologic techniques for the detection of alterations that occur in protein antigens were used to evaluate the immunogenicity of soybean glycinin after isolation, heat denaturation and pH alteration. The objective was to determine the effect of these agents on the immunogenic ability of this protein fraction. Immunologic assays performed on heat-denatured glycinin up to 80 degrees C in the presence of antinative glycinin serum demonstrated that glycinin retains its immunogenic properties. Above 90 degrees C this biological property begins to disappear, with protein insolubilization and epitope modification due to the conformational changes imposed by temperature. A reduction in immunogenicity also occurred when glycinin was taken to pH 2.0 (below its pl) and pH 11.00 (above its pl) and exposed to high temperatures in the presence of native antiglycinin serum. From these data one can conclude that, at extreme pH values, intramolecular reactions may occur which, in combination with the structural disorganization caused by high temperatures, may contribute to the reduction of immunogenicity.

Antigens↗
PubMed2005

Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

Animals↗
PubMed1999

Effect of local interleukin-2 treatment on spontaneous tumours of different immunogenic strength.

Transplantable tumour lines established from spontaneous tumours of BALB/c, CBA, and DBA/2 mice displayed different immunogenic strength. This report describes tumour susceptibility to interleukin-2 (IL-2) therapy in relation to tumour immunogenicity. The following tumour lines were used: X5, X6, and X9 mammary tumours of DBA/2, BALB/c, and CBA origin respectively, X7 carcinoma of BALB/c and X18 papilloma of CBA mice. Two spontaneous tumours of long transplantation history, SL2 lymphoma (SL2) of DBA/2 and Madison lung carcinoma M109 (M109) of BALB/c origin, were used as control systems. Experimental mice were transplanted with different inocula of tumour cells at day 0; treatment with IL-2 was initiated on days 1-3 or delayed until day 10 and consisted of daily injections of low doses of 5000 or 20,000 U/mouse given five times a week for a period of 3 weeks. Treatment of SL2 (2 x 10(4) cells injected i.p.) consisted of i.p. injections of 5000 or 20,000 U IL-2/mouse given on days 10-14 after tumour transplantation. IL-2 therapy of SL2-bearing DBA/2JIco mice resulted in a significant proportion of cures; however, no response to IL-2 treatment was achieved in SL2-bearing DBA/2CrIiw mice. BALB/c mice with the i.p. transplant of M109 responded to IL-2 treatment with 40% increase in lifespan. The low-dose IL-2 therapy of the five spontaneous tumours resulted, in general, in transient growth inhibition of the i.m. transplants of lines X5, X6, and X7 provided that IL-2 was administered locally. The therapeutic effect depended on the number of transplanted tumour cells, the best results being achieved at cell numbers close to the dose-inducing tumour growth in 50% of animals. We found that the spontaneously arising tumours responding to IL-2 treatment were all slowly growing and immunogenic (X6 and X7) or might have viral association (X5) and, as such, might express foreign antigens. The data suggest a correlation between tumour immunogenicity and the therapeutic effect. However, IL-2 can still exert some effect against tumours with negligible immunogenicity.

Animals↗
PubMed2005

Structural characterization and immunogenicity in wild-type and immune tolerant mice of degraded recombinant human interferon alpha2b.

PURPOSE: This study was conducted to study the influence of protein structure on the immunogenicity in wild-type and immune tolerant mice of well-characterized degradation products of recombinant human interferon alpha2b (rhIFNalpha2b). METHODS: RhIFNalpha2b was degraded by metal-catalyzed oxidation (M), cross-linking with glutaraldehyde (G), oxidation with hydrogen peroxide (H), and incubation in a boiling water bath (B). The products were characterized with UV absorption, circular dichroism and fluorescence spectroscopy, gel permeation chromatography, reverse-phase high-pressure liquid chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, and mass spectrometry. The immunogenicity of the products was evaluated in wild-type mice and in transgenic mice immune tolerant for hIFNalpha2. Serum antibodies were detected by enzyme-linked immunosorbent assay or surface plasmon resonance. RESULTS: M-rhIFNalpha2b contained covalently aggregated rhIFNalpha2b with three methionines partly oxidized to methionine sulfoxides. G-rhIFNalpha2b contained covalent aggregates and did not show changes in secondary structure. H-rhIFNalpha2b was only chemically changed with four partly oxidized methionines. B-rhIFNalpha2b was largely unfolded and heavily aggregated. Nontreated (N) rhIFNalpha2b was immunogenic in the wild-type mice but not in the transgenic mice, showing that the latter were immune tolerant for rhIFNalpha2b. The anti-rhIFNalpha2b antibody levels in the wild-type mice depended on the degradation product: M-rhIFNalpha2b > H-rhIFNalpha2b approximately N-rhIFNalpha2b >> B-rhIFNalpha2b; G-rhIFNalpha2b did not induce anti-rhIFNalpha2b antibodies. In the transgenic mice, only M-rhIFNalpha2b could break the immune tolerance. CONCLUSIONS: RhIFNalpha2b immunogenicity is related to its structural integrity. Moreover, the immunogenicity of aggregated rhIFNalpha2b depends on the structure and orientation of the constituent protein molecules and/or on the aggregate size.

Animals↗
PubMed1983

Thymus-independent immunogenicity in vitro of the divalent antigen DNP-polyethylene oxide.

Chemically simple and physically well-defined dinitrophenyl derivatives of polyethylene oxide (DNP-PEO) can be prepared in a wide range of forms and sizes. These materials were used to investigate the molecular basis of immunogenicity and the binding of the antigens to membrane-bound receptors. Both di- and multivalent DNP-PEO activate normal murine B lymphocytes to yield primary anti-DNP antibody response in vitro. The immunogenicity is dependent on the carrier chain length but independent of T cells. Responses comparable to those induced by DNP-conjugated polymerized flagellin are induced by divalent linear materials of medium molecular weights of about 60,000. A highly multivalent material is moderately immunogenic, but at much lower antigen doses than divalent materials. The carrier PEO does not affect B-cell responses to DNP-PEO or T-cell response to succinyl concanavalin A. Moreover, it shows no polyclonal mitogenicity at concentrations as high as 1 mg/ml. Studies of antigen binding to cell surface DNP receptors show that the strongly immunogenic materials of medium molecular weights have an appreciable tendency to bind bivalently and thus potentially to crosslink receptors. The binding of smaller, less immunogenic antigen appears predominantly monovalent.

Animals↗
PubMed1984

Tumor-specific immunity induced by somatic hybrids. IV. Relationship between immunogenicity and expression of surface tumor-associated antigens.

Semi-allogeneic hybrid clones were derived by fusion of the TEPC-15 plasmacytoma (H-2d) and mouse L cells of C3H (H-2k) origin. Three representative clones were chosen to study the relationship between the expression of different membrane antigens and their immunogenicities leading to protection of recipient mice from the parent TEPC-15 plasmacytoma. The level of surface tumor-specific transplantation antigens (TSTA) was measured by radioimmunoprecipitation with syngeneic anti-TSTA and by inhibition of anti-TSTA binding to the TEPC-15 tumor cells. The most immunogenic hybrid clone (LTC-1) expressed the highest level of TSTA and the weakly immunogenic (LTC-2) and nonimmunogenic (LTC-4) hybrid clones exhibited relatively low levels of TSTA on the surface. Moreover, the strongly immunogenic LTC-1 hybrid cells, but not the parent tumor cells, were effective in priming recipient spleen cells to generate TEPC-15 tumor-specific cytotoxic cells upon subsequent in vitro exposure to the TSTA-bearing cells. Therefore, the level of TSTA on the semi-allogeneic hybrid clones may play an important role in enhancing the immunogenicity of TSTA.

Animals↗
PubMed1988

Role of self carriers in the immune response and tolerance. XI. Correlation of Ia expression and interleukin-1 production with delivery of immunogenic signals in vivo by hapten-modified accessory cell-like tumor lines.

It was recently demonstrated that a lymphoid dendritic-like tumor, P388AD.2, presented hapten-modified self (HMS) in an immunogenic fashion even after injection via the normally "tolerogenic" intravenous (iv) route. To determine whether this property was unique to the P388AD.2 line, other hapten-modified tumors were administered iv and the result of their presentation was measured by changes in the number of splenic plaque-forming cells (PFC) following in vitro challenge with thymic-independent antigens. Of the six tumors tested, two (P388 and J774.5R) primed for augmented PFC responses, while four others (P388NA.10, P388D1, WEHI-231, and 70Z/3) did not. When these tumors were compared for Ia expression and production of interleukin-1 (IL-1), it was discovered that (1) all of the immunogenic tumors were Ia+ and IL-1 producing (IL-1+), although not all Ia+,IL-1+ tumors could elicit augmented PFC responses; (2) none of the tumors that were deficient in either Ia expression or IL-1 production could prime B-cell responses in vivo; and (3) the ability to augment PFC responses was proportional to the density of Ia on the immunogenic tumors. These results demonstrated that P388AD.2 was not the only tumor line capable of presenting HMS iv as an immunogen, and that the accessory cell phenotype is critical for the induction of an immunogenic response in vivo.

Animals↗
PubMed1989

Highly immunogenic regressor tumor cells can prevent development of postsurgical tumor immunity.

Highly immunogenic malignant cells form small tumors that spontaneously regress after initial growth because the tumor induces specific immunity. However, variants may arise during the initial tumor growth that lose antigens, grow progressively, often become the predominant tumor population, and eventually kill the host. These progressively growing variants usually have not lost all tumor antigens and remain susceptible to rejection by T cells specific for antigens present on the parental tumor and retained by the progressively growing variants. Thus, it would seem logical for therapy to actively immunize with the parental highly immunogenic tumor (or sublines made similarly immunogenic by tumor heterogenization) after maximal surgical removal of the growing tumor. However, the present findings suggest that such a strategy may be ineffective and have adverse effects: the parental highly immunogenic tumor cells, either remaining or reintroduced, may perpetuate unresponsiveness to both the parental and the variant tumor. These findings suggest that unless tumor-induced suppression is first abrogated, immunization with highly immunogenic tumor cells may be counterproductive because this maneuver may maintain preexisting immune suppression and prevent development of postsurgical tumor immunity.

Animals↗
PubMed1992

Evaluation of four different immunogens for the production of snake antivenoms.

Four different immunogens were used to produce polyvalent antivenom in rabbits to the venoms of Bothrops atrox, Crotalus atrox, Crotalus adamanteus and Crotalus durissus terrificus. The immunogens were: (1) unfractionated mixture of the four crude venoms, and three fractions of the mixture as follows, (2) HPLC gel filtration high (> 50,000) mol. wt fraction, (3) HPLC gel filtration medium (14,000-50,000) mol. wt fraction, and (4) HPLC gel filtration low (< 14,000) mol. wt fraction. The resultant immune sera were compared with commercial antivenom (Wyeth, polyvalent Crotalidae) for total IgG content, ELISA reactivities, patterns of Western blots and ability to neutralize lethal and local hemorrhagic activities of the four venoms. The results indicate that the rabbit antivenoms had significantly higher ELISA reactivity and blotting signals than Wyeth antivenom. However, neither ELISA nor Western blotting signals correlated with the ability of the antivenoms to neutralize the lethal or hemorrhagic activities of the venoms. The protective ability of the antivenoms varied considerably. In general, antivenoms generated by using fractionated venoms as immunogens exhibited greater protective ability than antivenom produced by using the mixture of four venoms as immunogen. Some of the antivenoms provided greater or comparable protective ability for certain venoms when compared to Wyeth antivenom. It appears that the use of certain venom fractions as immunogens is a promising alternative for production of effective antivenoms.

Animals↗
PubMed1988

Antigenic competition in the immune response against protein mixtures: strain-specific non-immunogenicity of Escherichia coli antigens.

Antigenic competition is argued to impair the immune response on the level of accessory cell-dependent antigen presentation to responsive T-cells (regulated by MHC encoded Ir gene products). A possible influence of these mechanisms on in vivo immunization with antigen mixtures was investigated by using cytoplasmic extracts of four different strains of Escherichia coli as antigen sources for immunizing rabbits. The immune response against these antigen mixtures was tested by crossed immune electrophoresis (CIE) and immunoblotting (IB) in a homologous system (a given antigen extract of one strain against the corresponding antisera) and in the heterologous system (antigen extract of one strain against the antisera of different other strains). Several proteins were non-immunogenic in the extract of one strain but elicited good antibody responses in other strains. One of the strain-specific non-immunogenic proteins was purified and revealed a normal immune response upon immunization. The data suggest that different antigenic competition effects are induced by different protein compositions of antigen mixtures. This strain-specific competition seems to determine the immunogenicity of certain molecules (and not only the immunogenic properties of the molecules themselves). Furthermore this method offers a practical approach to increase the antibody production against weak immunogens in antigen mixtures.

Animals↗