Showing papers on "Immunogenicity published in 1970"

The immunogenicity of antigen bound to the plasma membrane of macrophages

Abstract: Macrophages were cultured for several hours after a brief exposure to radio-iodinated keyhole limpet hemocyanin. Most of the hemocyanin taken up by the macrophages was rapidly catabolized and eliminated from the cell. A few molecules were retained on the plasma membrane of the cells for prolonged periods and were not subject to endocytosis and catabolism. These few molecules of hemocyanin bound to the plasma membrane were identified by observing the fixation of antibody fragments to macrophages at low temperature. The membrane-bound antigen, which could be removed by trypsin or EDTA, was of large molecular size, though heterogeneous. A great part of the immune responses of mice to hemocyanin bound to live macrophages could be abrogated by treatment of the macrophages in vitro with antibody or trypsin. Hence, most of the immunogenicity of hemocyanin bound to macrophages was attributed to the few molecules of antigen bound to the plasma membrane.

Metastasizing Mammary Carcinomas in Rats: Induction and Study of Their Immunogenicity

Abstract: Widely metastasizing mammary adenocarcinomas were isolated from methylcholanthrene-fed inbred young adult female W/Fu rats that had been splenectomized or thymectomized, and from those that had been both splenectomized and thymectomized. These tumors are transplantable and maintain their metastasizing capacity. They are either nonimmunogenic or less immunogenic than the nonmetastasizing conventional methylcholathrene-induced mammary tumors, which are highly immunogenic.

Immunogenicity of Ribonucleic Acid Preparations Obtained from Salmonella typhimurium

Abstract: Mice immunized with purified whole-cell ribonucleic acid (RNA), RNA from the bacterial “particulate” fraction, and ribosome-associated RNA obtained from Salmonella typhimurium were found to be resistant to subsequent challenge infection with virulent salmonellae. Chemically, the immunogenic nucleic acid fractions contained from 1 to 3% “contaminant” material defined (based on the mean of 19 different preparations) as protein (0.24%), deoxyribonucleic acid (0.43%), methyl pentose (0.64%), hexose (1.58%), and undefined carbohydrate (0.76%). Heptoses and lipoidal material were not detectable in any of the immunogenic preparations examined. Physically, the nucleic acid preparations, after analytical ultracentrifugation, exhibited three boundaries similar to those reported elsewhere in comparable systems: 4 to 5S, 16S, and 23S. An evaluation of the immunity induced by the ribosome-associated RNA established that the immune response was (i) comparable to that induced 15 days postimmunization with live salmonellae and by ribosomal vaccines, but greater at 30 days postimmunization than that in mice immunized with attenuated salmonellae; (ii) dependent on the quantity of immunogen administered; (iii) dependent on the size of the infective inocula; (iv) inhibited at 15 but not at 30 days postimmunization when the immunogenic nucleic acid preparations were incorporated into Freund's incomplete adjuvant, (v) reduced or lost by dialysis in relatively high or low immunizing doses, respectively; and (vi) unaffected by enzymatic treatment of the preparations with trypsin, deoxyribonuclease, Pronase plus pancreatic ribonuclease, or pancreatic ribonuclease alone. The possible mode of action of ribosome-associated RNA in inducing an immune response to subsequent challenge infection with the homologous organism is discussed.

Antigenic and immunogenic phage displayed mimotopes as substitute antigens: applications and limitations.

Abstract: The most exciting potential of phage displayed peptide libraries is to obtain small peptide molecules that mimic an antigen, at least with respect to a particular epitope. In addition to their interest as research tools, such mimotopes could in principle be useful as diagnostic tools or for eliciting antibodies to a predefined epitope. However, the reduction of the phage insert sequence to a short peptide that can compete with the antigenic and in particular with the immunogenic properties of the natural antigen faces considerable difficulties. This review assesses critically the antigenicity of phage displayed peptides as free peptides and in different molecular environments. The difficulties to use mimotopes to induce antibodies that bind to the natural antigen (crossreactive immunogenicity) and the considerable discrepancy between antigenicity and immunogenicity of phage-derived peptides are discussed. Peptides selected with antibodies from phage displayed random peptide libraries have raised considerable expectations as low molecular weight substitutes of the natural antigen. This review will focus on the results of phage displayed random peptide libraries screened with antibodies specific for proteins, carbohydrates and nucleic acids and critically examine how the above expectations have been met.

Studies on the immunogenicity of antigen-antibody precipitates. II. The suppressive effect of anti-carrier and anti-hapten antibodies on the immunogenicity of dinitrophenylated human gamma G globulin.

Abstract: Guinea pigs immunized with dinitrophenylated human γG globulin (DNP-HGG) formed precipitating antibody which reacted with the immunizing protein, with DNP coupled to heterologous carriers, and, in many cases, with the carrier (HGG) molecule itself. Delayed hypersensitivity reactions were directed almost exclusively against the DNP-HGG complex. When animals were immunized with the same quantities of DNP-HGG bound in antibody excess immune precipitates to either anti-DNP or anti-carrier (anti-Fc) the humoral responses to both the DNP and the carrier determinants were markedly reduced. On the other hand such precipitates were effective in initiating cell-mediated responses; delayed hypersensitivity skin testing revealed that these animals were indistinguishable in this respect from animals sensitized with “free” DNP-HGG. Animals rendered unresponsive to either the carrier (HGG) or the hapten molecules, by intravenous administration of either HGG or dinitrophenylated bovine serum albumin, produced minimal responses to simultaneous administration of DNP-HGG in complete Freund9s adjuvant. In these animals both delayed hypersensitivity reactions and circulating antibody formation were markedly reduced. The results suggest that the “processing” of antigen to initiate cell mediated and humoral responses proceeds, at a very early stage, along different pathways.

Virulence and immunogenicity of mutant strains of Salmonella typhimurium.

Abstract: The virulence of R-mutants derived from the S-strain Salmonella typhimurium 395 MS has been investigated and compared with their phage pattern, chemical composition of the lipopolysaccharide, agglutination by O-specific serum and absorption of O-specific antibodies. No strict relationship between phage pattern or chemical composition and virulence could be established. The most virulent mutants (R4a, R9) seemed to have O-specific antigen at their surface, whereas no O-specific antigen could be demonstrated in the least virulent one (R10), which also showed strong spontaneous agglutination. Two rough-resistant mutants, R5 and R6, with large quantities of O-specific antigenic determinants at their surface showed low and almost no virulence, respectively. Mucin reduced the lethal dose considerably, the factors ranging between 102 and 10-5. Mice surviving for 5 weeks after infection often demonstrated a chronic disease with enlargement of the spleen and sometimes yellow-white patches in the spleen and in the liver. Mice surviving doses of R-bacteria that might be lethal to some animals in the same group often survived challenge with S-bacteria. Particularly R9, a galactose-4-epimerase-less mutant, gave a high degree of protection in surviving mice.

Immunogenicity of oncolysates obtained from Ehrlich ascites tumors infected with vesicular stomatitis virus.

Abstract: Inbred A2G mice could be immunized against Ehrlich ascites (EA) tumor with lysates prepared from EA cells infected with vesicular stomatitis virus (VSV). The immunizing power of such lysates could be abolished by rabbit antiserum directed against egg grown VSV. This inhibition was specific: A chicken anti-fowl plague antiserum inhibited the immunogenicity of fowl plague EA cell lysates, but not of VSV lysates. Conversely, a rabbit anti-VSV antiserum inhibited the immunogenicity of VSV lysates, but not of fowl plague lysates. Pre-immunization of animals with live egg grown VSV resulted in a secondary anti-tumor response upon immunization with VSV tumor cell lysate.

Antigenic site(s) of synthetic human calcitonin M.

Abstract: STEPWISE synthesized peptides of relatively small size and defined structure serve as excellent model compounds to evaluate the structural features which determine their reactivity with antibody. The availability of synthetic, immunogenic and biologically active oligopeptides may, furthermore, facilitate a study of the molecular properties which confer immunogenicity and make it feasible to compare the structures which control immunological specificity and biological activity.

The Immune Response to Heterologous Red Cells in Mice: V. The Effect of Cyclophosphamide and Cortisone on Antigenic Competition

Abstract: The effects of cyclophosphamide and cortisone acetate were examined in a model of antigenic competition between sequentially administered non-cross-reacting red cells from different species. In control mice receiving no drug, the relative immunogenic potency of heterologous red cells given with the first injection failed to determine the degree of unresponsiveness to subsequently injected unrelated cells. However, susceptibility to the suppressive action of previously administered erythrocytes was inversely related to the immunogenicity of the second antigen. Cyclophosphamide given 1 day after the initial red cell injection completely blocked competitive inhibition. On the other hand, impaired reactivity to the second of two sequentially administered antigens was further depressed by cortisone. The results are discussed in terms of targets of drug action and possible sites of antigenic interference.

Antitoxic immunity in experimental cholera: observations with purified antigens and the rat foot edema model.

Abstract: The recently introduced choleragen-induced rat foot edema model has been employed as a bioassay for evaluating the immunogenicity of three purified preparations containing cholera exo-enterotoxin antigen, choleragen, choleragenoid, and Formalin-treated choleragen (formagen). The results indicated that choleragen evoked antitoxic immunity. Both the degree of resistance to challenge and the serum antibody levels of immunized animals were found to be related to the immunizing dose. Responses to the natural toxoid, choleragenoid, were erratic: some animals responded well and some failed to respond with either serum antibody or resistance to challenge. On the other hand, the artificially prepared toxoid, formagen, was found to be superior to the parent toxin in immunogenicity. Resistance to the choleragen-induced rat foot edema could be transferred passively by means of antibody-containing serum from previously immunized animals. Each of the antigens induced a state of hypersensitivity manifested by an immediate edematous response to challenge with either choleragen or choleragenoid. This condition, which was also passively transferable, suggests that untoward reactions should be anticipated in people receiving multiple doses of immunogens containing the cholera exo-enterotoxin antigen. Some of these observations were repeated, in a preliminary fashion, in an apparently equally suitable mouse foot edema model.

Immunogenicity of rhinoviruses.

Abstract: SummaryUniformly successful production of rabbit rhinovirus antisera depended on production of immunogens with virus concentrations of at least 107 pfu/ml. Response in pairs of rabbits immunized with the same antigen appeared to be remarkably uniform, and maximum antibody titers were attained at 38 to 45 days after beginning a relatively simple immunization schedule (1 im + 4 iv injections). Anticellular antibody levels were usually low in comparison to rhinovirus antibody titers and such antibody could be removed easily by adsorption with suspensions of whole HeLa cells without reducing the level of antiviral antibody.The authors express their appreciation to Prudence Moeller Olsen, Marie Morasch, and Byron Doneen for valuable technical assistance.

Quantitation of the Antigenicity and Immunogenicity of Purified Foot-and-Mouth Disease Virus Vaccine for Swine and Steers

Abstract: The antigenicity and immunogenicity of a purified preparation of foot-and-mouth disease virus [type A12, strain 119 (FMDV A-119)] inactivated with 6.0 mmN-acetylethylenimine at 37 C were compared in swine and steers. Three antigen doses were tested, 640, 160, and 40 ng. In accordance with findings for guinea pigs, as previously determined by dose-response curves, as little as fourfold changes in antigen in the region of the minimum effective dose produced marked differences in the serological and immune responses of swine. The minimum effective dose of antigen for antibody formation in swine and guinea pigs, as determined by mouse median protective dose (PD50) values, was 160 ng. The minimum immunogenic dose for swine was also 160 ng. The vaccinated swine were challenged with either FMDV A-119 or with heterologous subtype A24 strain Cruzeiro or type A strain A-CANEFA-1. Those immunized with 640 ng of antigen were about equally immune to the three challenge viruses; most swine having a mouse PD50 value of 2.0 or greater were immune regardless of which strain was used for challenge. In steers, the smallest dose tested, 40 ng, was satisfactory in eliciting circulating antibodies and immunity. Physical and biological tests indicated that the antigen used in the vaccine is stable for at least 9 months at 4 C.

Differences in antibody responses of mouse strains to enterobacterial common antigen.

Abstract: SummaryThe genetic influence of various mouse strains on antibody response to the common antigen (CA) of Enterobacteriaceae was determined. Four strains of mice, three inbred and one random-bred, were injected ip with CA of E. coli 014 or 0111, with or without incomplete Freund's adjuvant. CA antibody titers, determined by hemagglutination tests, revealed the following: CBA/St and C57BL/6Ha mice responsed significantly better than did DBA/2Jax and Swiss albino mice; ethanol-soluble CA from E. coli 0111 was a better immunogen than was CA from E: cold 014; adjuvant did not enhance immunogenicity of CA in responding mice; highest titers were noted 5 days after the third injection of CA, persisted for 2 weeks, and declined by the end of 2 months; and a subsequent injection of CA failed to elicit a secondary response.

Enhanced immunogenicity in mice of a purified, tween-ether-treated influenza vaccine.

Abstract: The immunogenic response of mice vaccinated intranasally or subcutaneously with increasing doses of a purified, concentrated intact A(2)/Taiwan influenza vaccine or its Tween-ether derived vaccines was compared Immunogenicity was measured by serum neutralization and hemagglutination-inhibition antibodies, lung lesions scores, and protection against respiratory challenge with live airborne influenza virus Intact (untreated) vaccine, Tween-ether-treated (ET) vaccine, and the isolated hemagglutinins (HA) provided protection and stimulated homologous antibody response at the 35- and 70-chicken cell agglutination (CCA) unit level At a lower dosage level, the vaccines administered by the subcutaneous route appeared to confer better protection The ET vaccine was superior to intact virus or HA vaccines when administered subcutaneously The minimum amount of the HA and intact vaccine given subcutaneously that protected mice against respiratory challenge was 7 CCA units (35 units injected twice) compared to 07 CCA units (035 units injected twice) for the ET vaccine No heterologous antibody to the A/PR/8/34 or B/Mass/3/66 was noted Low-level serum-neutralizing antibody was found against the A(2)/Japan/170 strain but, despite high levels of homologous A(2)/Taiwan/64 antibody, no cross-reactivity was found with the recent A(2)/Hong Kong/68 variant

pH Sensitive Liposomes Enhances Immunogenicity of 19 kDa Carboxyl- terminal Fragment of Plasmodium Falciparum

Abstract: The Carboxyl-terminal 19 kDa fragment of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1 19 ) was delivered directly into the cytoplasm via pH sensitive liposome. In the present study, we have reported the preparation and characterization of PfMSP-1 19 encapsulated pH-sensitive liposomal formulations using oleyl alcohol (OAlc) in combination with egg phosphatidylcholine (EPC) as the membrane destabilizing components. Furthermore, the OAlc-containing liposomes were evaluated for the intracellular cytosolic delivery of PfMSP-1 19 and as is evident from the results obtained; promising and significant immune responses were obtained by the cytosolic delivery of the malaria antigen through pH sensitive liposome and in association with alum this carrier vehicle may be used as a natural adjuvant. Moreover, after intramuscular immunization of PfMSP-1 19 loaded pH sensitive liposomes, into Balb/c mice, the significant and perdurable IgG responses were obtained, as compared to conventional liposome loaded with PfMSP-1 19 and comparative evaluations have been marked with alum adsorbed malaria antigen. This may be attributed to good immuno-adjuvant action of pH sensitive liposomes, which are reported to enhance the immunogenicity of a soluble malaria antigen and present study might open new ways for the feasibility for the development of blood stage malaria vaccine.

Immunogenicity of purified venezuelan equine encephalitis virus inactivated by ionizing radiation.

Abstract: Purified and concentrated Venezuelan equine encephalitis (VEE) virus derived from tissue cultures, rendered noninfectious by ionizing radiation with retention of in vitro serological activity, also retained a high level of immunogenicity. In mice, fluid vaccines afforded excellent protection against lethal challenge with homologous Trinidad strain VEE virus. A direct relationship was observed between concentration of vaccine or number of injections and survival. One intraperitoneal inoculation of undiluted vaccine protected essentially all mice challenged 21 days later with 100,000 mouse intraperitoneal LD50 of virus. Similarly, mice receiving three injections of vaccines diluted 1:100 were completely protected. Noninfectious VEE virus preparations combined with adjuvant 65, a nontoxic metabolizable vehicle, were likewise very effective in protecting mice immunized intraperitoneally or subcutaneously against lethal challenge. Guinea pigs immunized subcutaneously with adjuvant-combined vaccine survived lethal challenge of 1,000,000 guinea pig intraperitoneal LD50.

Induction of antibody synthesis. Effect of blocking defined determinants of an antigen.

Abstract: Rabbit antibody specific for bovine γ-globulin (BGG) and for the dinitrophenyl group (DNP) was used to block defined determinants of BGG—DNP, and the immunogenicity of antibody-complexed BGG—DNP in rabbits was compared with that of BGG—DNP Antibody-complexed BGG—DNP was less immunogenic, eliciting less antibody reactive with BGG—DNP However, BGG-specific antibody, in contrast to DNP-specific antibody, suppressed primarily the induction of antibody specific for the BGG determinants of BGG—DNP This finding suggests: (1) that induction of antibody specific for a given determinant of an antigen requires the active participation of that determinant as an inducer, and (2) that the immunosuppressive action of antibody is determinant-specific and not antigen-specific The immunogenicity of antibody-complexed sheep erythrocytes was also studied in mice Rabbit antibody to sheep erythrocytes, in different amounts, was used to block determinants on the surface of sheep erythrocytes The agglutinin response was inversely proportional to the amount of antibody used to complex the erythrocytes This finding supports the role of determinants as inducers of antibody formation and indicates that the immunogenicity of an antigen is a function of the number of determinants it carries in an accessible reactive state

The secondary antibody response in tissue culture. IV. Studies of the in vivo and in vitro antigenicity of native, aggregate-free and aggregated human gamma globulin in rabbits.

Abstract: The antigenicity of native, aggregate-free and heat-aggregated HGG was investigated in vivo and in vitro, using the cell culture and fragment culture systems. Although the aggregate-free material displayed very low immunogenicity in vivo, its antigenicity was markedly enhanced if injected along with Freund's adjuvant. Results of cell culture experiments, using immune spleen cells, paralleled the in vivo results in that the aggregated HGG was highly blastogenic whereas the aggregate-free HGG could not induce blastogenesis of the immune cells. Results of an opposite nature derived from the fragment culture experiments in that aggregate-free HGG could readily induce a secondary immune response in vitro whereas the aggregated HGG was unable to do so. The significance of these results is discussed.

Immunogenicity of Human γ Globulin Bound to Macrophages after Inhibition of Rna Synthesis

Abstract: Macrophages obtained from the peritoneal cavity of mice were incubated in vitro with human γ globulin (HGG), and then transferred to allogeneic recipients that were boosted 30 days later with soluble antigen. Recipients made better primary and secondary responses to HGG bound to macrophages than did animals immunized with soluble HGG. The immunogenicity of HGG in macrophages was moderately decreased by treatment of the cells with concentrations of actinomycin-D that inhibited RNA synthesis. These results are discussed in the light of the possible importance of informational RNA and of increased immunogenicity of macrophage-bound antigen in the immunologic response.

Antigenic properties of mono-dinitrophenyl-derivatives of bacitracin A in guinea-pigs.

Abstract: The immunogenicity of the three mono-DNP-derivatives of bacitracin A as compared with the immunogenicity of the tri-DNP-derivative of bacitracin and of bacitracin itself was investigated in randomly bred guinea-pigs. PCA and an in vitro binding assay (a modified Farr technique) were both employed for antibody detection. All of the DNP-derivatives were able to stimulate formation of anti-DNP antibodies. Mono-DNP(ornithine)-bacitracin and tri-DNP-bacitracin induced antibody production in almost all the animals; mono-DNP(histidine)-bacitracin and mono-DNP(isoleucine)-bacitracin induced antibodies in only one-half and one-fifth of the animals, respectively. No antibodies against bacitracin could be detected in animals injected with this polypeptide or with its DNP-derivatives. Investigation by PCA of the relative reactivities of the anti-DNP-bacitracin antibodies for each of the mono-DNP-derivatives of bacitracin revealed that different populations of antibodies are elicited by each of these substances. Specificity extending to the amino acid on which the DNP group is attached would appear to be present in the populations of antibodies elicited by both mono-DNP(ornithine)-bacitracin and mono-DNP(isoleucine)-bacitracin. Additional evidence would indicate that the specificity of the anti-DNP-bacitracin antibodies may extend beyond the DNP-amino acid determinant.

Structure and immunogenicity of synthetic antigens.

Abstract: Synthetic antigens are often valuable tools in immunological research. They are usually linear or branched polypeptides, prepared by polymerization of N-carboxy-α-amino acid anhydrides or by polymerization of defined oligopeptides. Owing to their great variability, these simple antigens allow a systematic study of the chemical and physical parameters involved in immunogenicity, i.e. the ability of a substance to initiate an immune response in higher animals. The study of very simple synthetic antigens made possible the first detailed analysis of genetic factors controlling the immunogenicity of a substance. The results have led to a better understanding of many immunological phenomena, and have helped to explain the complex processes initiated by antigens that lead to a specific immune response.