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Biomedical subjects

C A Morrison

Publications and source records attributed to C A Morrison.

At least 19 recordsLinked to original sources

Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine models and in protection against a bovine parasitic infection.

Potent immunological adjuvants are urgently required to complement subunit protein and peptide vaccines in prophylactic and therapeutic vaccination. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T-helper cells, were tested as a target for the enhancement or immune responses to vaccine antigens. Enzymic oxidation of cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. In pilot protection studies with a glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation containing NAGO as sole adjuvant agent proved very effective in inducing protection. In terms of protection in individual animals, NAGO alone was better than Quil A emulsified in squalene Montanide (five of eight animals were protected better than 80% by NAGO; four of eight animals were protected better than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM). QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65% mean protection). NAGO proved more effective in murine models when combined with muramyl dipeptide, but this combination has yet to be tested in protection studies.

Acetylmuramyl-Alanyl-Isoglutamine

Effect of immunization against synthetic peptide sequences of the alpha N-subunit of bovine inhibin on ovulation rate, gonadotrophin concentrations and fertility in heifers.

The effects of immunizing cattle against either of two peptides from the amino terminal peptide (alpha N) of the alpha 43-subunit of bovine inhibin on ovulation rate, gonadotrophin concentration and fertility were investigated. Two peptide sequences from the alpha N-subunit of bovine inhibin (P1N, bI alpha-(8-20) and P2N, bI alpha-(153-167)) were synthesized and conjugated to human serum albumin (HSA). Hereford-cross heifers (n = 5 per group) were given an initial injection of 3 mg of one of the peptide conjugates, followed by three booster injections (1.5 mg) at intervals of 11 weeks. Control heifers (n = 5) were injected with HSA only. Blood samples were taken once a week to measure antibody titre and every hour at about the time of the first oestrus and during the mid-luteal phase after the second booster injection, to measure FSH and LH concentrations. Ovulation rate was measured by ultrasonography. Gonadotrophin concentrations were analysed for four periods relative to the peak (time = 0 h) of the preovulatory LH surge as follows: pre-surge: -16 to -5 h; surge: -4 to 4 h; post-surge: 5 to 16 h and a period of 12 h during the mid-luteal (days 10-12) phase. Antibodies that bound to the individual peptides were generated and the ovulation rate increased (P < 0.05) in immunized heifers. Control heifers had one ovulation at all ovulatory cycles monitored. In group P1N, one heifer had two ovulations at each of the six cycles monitored, while another heifer had two ovulations at one cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Vaccination of sheep against Fasciola hepatica with glutathione S-transferase. Identification and mapping of antibody epitopes on a three-dimensional model of the antigen.

The glutathione S-transferases (FhGST) of the liver fluke Fasciola hepatica have been identified as novel vaccine candidates that protect sheep against a fluke infection. With the use of overlapping peptides covering the predicted amino acid sequences of four FhGST cDNAs, we have defined the linear epitopes recognized by polyclonal antibody from sheep vaccinated with FhGST. Dominant and minor epitopes were found to be present on all four of the sequences although some epitopes were shown to be specific to particular FhGST. A high percentage of the FhGST peptides were found to be antigenic although considerable variability in response to the peptides was observed among the animals. This analysis was extended to the IgG1 and IgG2 response at the peptide level. Based on the recently solved crystal structure of the rat mu-class GST 3-3, a three-dimensional model of one of the FhGST sequences was generated that allowed the predicted spatial localization of defined epitopes. Most epitopes were localized on regions of high flexibility and accessibility. A comparison of epitopes on FhGST with the B cell epitopes on Sm28, a 28-kDa GST from Schistosoma mansoni, has found few similarities. There was no correlation between an antibody response to linear peptide epitopes and the level of protection induced in sheep by vaccination with FhGST.

Amino Acid Sequence

Immunization of bull calves with a GnRH analogue-human serum albumin conjugate: effect of conjugate dose, type of adjuvant and booster interval on immune, endocrine, testicular and growth responses.

Bull calves were immunized with GnRH analogue-human serum albumin (HSA-Cys-Gly-GnRH) conjugate to determine the effects of dose, adjuvant type and interval between primary and booster injections on plasma testosterone and LH concentrations, and testes and body growth. Friesian bull calves aged between 8 and 10 weeks (n = 72) were blocked according to age and weight and, within block, randomly assigned to 12 treatment combinations (n = 6 per treatment combination) in a 3 x 2 x 2 factorial plan. Main effects were (i) conjugate dose (0.0, 0.1 or 1.0 mg HSA-Cys-Gly-GnRH), (ii) adjuvant (diethylaminoethyl-dextran or non-ulcerative Freund's adjuvant), and (iii) interval between primary (day 0) injection and booster injection (day 28 or 56). Plasma testosterone and LH concentrations and antibody titres were determined in blood samples collected at 14 day intervals during the experiment (140 days). Testicular measurements were taken in situ every 28 days. Antibody titres (% binding at 1:160 dilution) were > or = 10% 28 days after booster injection and remained high for 140 days in 47 of 48 GnRH-immunized bulls. The mean titre was higher (P < 0.05) in response to the 1.0 mg dose compared with the 0.1 mg dose (37.7% versus 29.6% binding, respectively; pooled SED 2.55%). Mean LH and testosterone concentrations were reduced (P < 0.05) in immunized animals compared with controls. However, the 1.0 mg dose decreased mean testosterone concentrations by a greater extent (P < 0.001) than either the 0.1 mg or 0.0 mg doses. Testes length and depth, and scrotal circumference were decreased (P < 0.001) in immunized animals compared with controls; however, the 1.0 mg dose decreased (P < 0.001) testes parameters to the greatest extent. There was no effect of conjugate dose on average daily gain in body mass. It is concluded that (i) dose of conjugate, type of adjuvant and interval between primary and booster injections affected antibody titres, (ii) the use of 0.1 or 1.0 mg of HSA-Cys-Gly-GnRH decreased LH and testosterone concentrations, and testicular development throughout the experiment, without adversely affecting body growth, and (iii) an effective protocol is 1.0 mg GnRH-HSA conjugate, given in the adjuvant diethylaminoethyl dextran, with a primary-booster interval of 56 days.

Adjuvants, Immunologic

Active immunization against prostaglandin F2 alpha: effect of conjugate dose and booster interval on antibody titers and estrous behavior in postpubertal beef heifers.

To optimize the prostaglandin F2 alpha (PGF) immunization protocol (conjugate [PGF-human serum albumin; PGF-HSA] dose and immunization regimen) to achieve prolonged suppression of estrous behavior (EB) in beef heifers, 56, 14-mo-old cyclic heifers were assigned (n = 7 per treatment) to eight treatments: 1) 3.3 mg of PGF-HSA on d 0 (single); 2) 3.3 mg of PGF-HSA on d 0 and 28 (booster; B); 3) as (2) except on d 0 and 55; 4) as (2) except on d 0 and 83; and 5 to 8) as in Treatments 1 to 4 except using 10 mg of PGF-HSA. The adjuvant was diethylaminoethyl-dextran, and duration of the experiment was 170 d. Heifers were checked twice daily for EB. A persistent corpus luteum (CL) was considered present when progesterone (P4) was > or = .5 ng/mL for > or = six consecutive samples (every 3 to 4 d). Data were analyzed using ANOVA for a factorial plan. All heifers produced plasma antibody titers (samples every 2 wk) against PGF (peak range: 7 to 84% binding at 1: 1,250). There were no effects (P > .10) of conjugate dose and no interactions between dose and immunization regimen for any variable; therefore, data were combined across dose. Mean and peak titers were greater (P < .05) in heifers in 55- and 83-d B treatments than those in single immunization and 28-d B treatments. Overall, 48/55 heifers formed a persistent CL (41/41 for B heifers). In the single, and 55- and 83-d B treatments, 23/42 heifers formed persistent CL in response to single/primary immunization. There was no difference between immunization regimens in duration (133 +/- 4.4 d) of persistent CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Histochemical analysis of rat testicular glycoconjugates. 3. Non-reducing terminal residues in seminiferous tubules.

Lectins of Helix pomatia (HPA), Glycine max (SBA), Vicia villosa (VVA), Dolichos biflorus (DBA), Ulex europaeus (UEA-1), Tetragonolobus purpureus (LTA), Griffonia simplicifolia (BSA-1B4), Maclura pomifera (MPA), Sambucus nigra (SNA) and Maackia amurensis (MAA) were used to explore the distribution of saccharides characteristic of non-reducing termini of O- and N-linked glycoprotein glycans in the seminiferous tubules of rat testis. Sialyl residues (both alpha 2,3- and alpha 2,6-linked, as shown by MAA and SNA respectively) and alpha-L-fucosyl residues (shown by UEA-1 and LTA) were expressed on spermatogonia, spermatocytes and spermatozoa, but not on spermatids. In contrast, 2-deoxy-2-acetamido-alpha-D-galactosyl termini were abundant on spermatozoa, but not on any of their precursors (as shown by HPA, SBA and VVA). All occurred on both O- and N-linked glycans. Sertoli cells expressed small amounts of fucose and alpha 2,3-linked sialic acid, and abundant alpha 2,6 sialyl residues, largely on N-glycans. alpha-Galactosyl residues were readily detected on the tubular basement membrane, but not elsewhere.

Animals

Effect of immunization against synthetic peptide sequences of bovine inhibin alpha-subunit on ovulation rate and twin-calving rate in heifers.

Three peptide sequences from the bovine inhibin alpha-subunit (P1: 18-30; P2: 63-72 and P3: 107-122) were synthesized and conjugated to human serum albumin (HSA). Hereford cross-heifers (n = 5 per group) were injected with 3 mg of one of the peptide conjugates, followed by three booster injections at intervals of 11 weeks. Control heifers (n = 5) were injected with HSA only. Antibodies recognizing both the individual peptides and 32 kDa bovine inhibin were generated and ovulation rate was increased in peptide immunized heifers. In group P1, 1 of 5 heifers responded with an increased ovulation rate whereas in groups P2 and P3, 5 of 5 and 4 of 5 heifers, respectively, had an increased ovulation rate. In group P2, in the first oestrous cycle following booster injections 2 and 3, 4 of 5 and 3 of 5 heifers, respectively, responded with twin ovulations, whereas a fourth heifer had three ovulations following booster injection 3. After breeding following booster injection 3, 3 of 5 heifers in group P2 and 1 of 5 in group P3 gave birth to twin calves. This study demonstrates the potential of immunizing against synthetic peptide sequences of the alpha-subunit of bovine inhibin to increase ovulation and twinning rates in cattle.

Animals

Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay.

An immunoradiometric assay (IRMA) for the measurement of insulin-like growth factor-II (IGF-II) in human plasma has been developed, optimized and evaluated clinically in normal subjects and patients with disorders of the GH/IGF-I axis. Six monoclonal antibodies (MAbs) to recombinant human IGF-II (rhIGF-II) were produced, all of which had low cross-reactivity with rhIGF-I (< 0.01%) and insulin (< 0.01%). Compatibility of pairs of MAbs was tested in two-site IRMAs using three radioiodinated MAbs and three MAbs linked to Sephacryl S-300 (with separation of bound and free radiolabelled MAb by sucrose layering). Seven pairs of MAbs bound rhIGF-II and the combination of 125I-labelled W3D9 and W2H1 linked to solid phase was selected. The optimized assay had a completion time of 4 h, a minimum detection limit of 30 ng/ml (2.5 standard deviations from the zero standard) and detected a single peak of endogenous IGF-II in normal plasma which co-eluted with rhIGF-II after acid gel chromatography. IGF-II was measured in formic acid/acetone extracts of plasma from 16 normal subjects (mean 685, range 516-1008 micrograms/l), four acromegalic patients (mean 637, range 553-700 micrograms/l), fourteen patients with type-1 diabetes (mean 635, range 247-753 micrograms/l), nine patients with uraemia (mean 423, range 78-850 micrograms/l), and three patients with Laron-type GH insensitivity (75, 35 and 36 micrograms/l). No significant fluctuations were detected between samples obtained hourly from 08.00 to 19.00 h in normal subjects. Low levels of IGF-binding proteins (IGFBPs) remaining in plasma extracts may interfere with the measurement of IGF-II and give rise to falsely elevated IGF-II levels in radioimmunoassays or falsely suppressed levels in IRMAs. Such interference did not occur with the IRMA when used to measure IGF-II in extracts from normal subjects, acromegalic patients and patients with type-1 diabetes, and the addition of excess rhIGF-I in order to displace IGF-II from residual IGFBPs had no effect on IGF-II measurements in these samples. However, levels of IGF-II measured in extracts from patients with Laron-type GH insensitivity and patients with uraemia increased markedly after preincubation with excess rhIGF-I. The accurate measurement of IGF-II by IRMA in extracts from these subjects therefore requires the displacement of IGF-II from IGFBPs prior to assay. We conclude that, in contrast to radioimmunoassays, the two-site IRMA developed here provides a practical, rapid and specific method for the measurement of IGF-II in human plasma.

Antibodies, Monoclonal

Histochemical analysis of rat testicular glycoconjugates. 1. Subsets of N-linked saccharides in seminiferous tubules.

The distribution of N-linked glycans in rat testis has been probed using a panel of lectins derived from Galanthus nivalis (snowdrop, GNA), Canavalia ensiformis (jack bean, Con A), Lens culinaris (lentil, LCA), Pisum sativum (garden pea, PSA) and Phaseolus vulgaris, erythro- and leucoagglutinins (kidney bean, ePHA and lPHA). Several classes of N-linked glycan were identified in the spermatogenic series, and during differentiation into spermatozoa they altered in both their pattern of distribution and relative abundance. A population of tetra-antennary, non-bisected, complex glycans, detected by lPHA, was lost during the transition from spermatogonia to spermatocytes, while high-mannose structures were acquired; these were most abundant in spermatocytes, as were bi- and tri-antennary complex, non-bisected glycans, the latter becoming increasingly abundant on acrosomes and spermatozoa. Their bisected counterparts were more generally expressed throughout spermatogenic cells, although marked localization onto acrosomes and nuclear caps was again seen. Transition from spermatocytes to spermatids involved mainly changes of the acrosomal granule and nuclear cap, which were carried through to the final stages of differentiation. Sertoli cell surfaces and cytoplasmic granules showed a high level of N-glycan expression.

Animals

Histochemical analysis of rat testicular glycoconjugates. 2. Beta-galactosyl residues in O- and N-linked glycans in seminiferous tubules.

Rat testes have been examined with a panel of lectins that bind specifically to oligosaccharide sequences having terminal or subterminal beta-galactosyl residues in O-linked glycans, or in the outer chains of complex N-linked glycans: Arachis hypogaea (peanut, AHA), Erythrina cristagalli (coral tree, ECA), Ricinus communis (castor bean, RCA120) and Abrus precatorius (jequirity bean, APA) agglutinins. Pretreatment of sections with neuraminidase, beta-galactosidase and removal of alkali-labile O-linked sequences by beta-elimination allowed the structure of these glycans to be further explored. In spermatogonia and spermatocytes there was little evidence of glycans terminating in beta-galactosyl residues, although these were present at non-reducing terminals as sialylgalactosides. The acrosome contained two subsets of O-linked glycans terminating in sialylgalactosides, while the nuclear cap showed at least two subsets of N-linked sialylgalactosyl as well as O-linked glycans. Spermatozoa exhibited minor changes in the pattern of glycosylation, although the overall pattern of beta-galactosyl expression was similar. Binding to Sertoli cells showed the presence of some unsubstituted beta-galactosyl terminals on O-linked glycans but few such N-linked residues, while terminal beta-galactosides were scanty in tubular basement membranes.

Animals

The fate of abstracts submitted to a cancer meeting: factors which influence presentation and subsequent publication.

Abstracts that are published in the proceedings of meetings receive minimal peer-review, but may be referenced or used to make decisions about management of patients. We have studied factors which influence the probability of acceptance for presentation, and of subsequent publication of articles, from abstracts included in the Proceedings of the American Society of Clinical Oncology (ASCO). From a random sample of 197 abstracts submitted to the 1984 meeting, 81 were accepted for presentation and a Cancerline computer search revealed 103 papers that were published subsequently in peer-reviewed journals. Communication with authors of the remaining abstracts led to identification of 12 additional articles that had been published. Major reasons for non-publication were insufficient priority or lack of time, funds or other resources. Abstracts which reported 'positive' results were more likely to be presented than those reporting 'negative' results (60% vs. 35%, p = 0.03) and to lead to subsequent publication (74% vs. 32%, p = 0.0001). Of the 81 abstracts in our sample that were selected for presentation at the meeting, 63 (78%) led to publications, compared to 45% (52/116) of those not selected (p = 0.00001). There were no significant differences in the frequency of citation of abstracts that did or did not lead to subsequent publications. We made detailed comparisons of abstracts and subsequent papers for 18 randomized phase III trials. For 15 studies (83%), there was good correlation between the conclusions of the article and of the abstract.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstracting and Indexing

Identification and partial purification of serum growth hormone binding protein in domestic animal species.

The chemical nature and variations in serum concentrations of growth hormone binding protein (GHBP) from humans, rabbits, and rodents have been reported. To date little is known about the GHBP of domestic animals. Therefore, we initiated these studies to determine whether a serum GHBP was present in domestic animals and to purify the binding protein (BP) from serum of selected species. Using a dextran-coated charcoal separation assay, specific growth hormone (GH) binding was demonstrated in ovine, bovine, chicken, human, goose, porcine, and equine serum (listed in sequence from lowest to highest binding). Variation in BP activity was relatively high, both within and between species. Yearling ewes had higher serum GHBP than either prepubertal (4 mo) or older (5 yr) ewes. The GHBP was partially purified from chicken, ovine, and porcine serum using GH affinity chromatography. These BP had high affinity (Ka = 2 x 10(8) to 2 x 10(9) L/mol, depending on species) and low capacity (2 x 10(-10) to 5 x 10(-11) mol/unit of protein) for human GH but showed lower binding affinity for homologous GH (Ka = 2 x 10(7) L/mol). The porcine GHBP had the highest and ovine GHBP the lowest affinity for human GH. Other heterologous somatotropic hormones, ovine placental lactogen, and ovine GH displayed higher binding affinity to chicken and pig BP than the respective homologous hormones. Further chromatographic purification of the porcine GHBP resulted in an additional 1,000-fold purification. The estimated molecular weight of porcine GHBP is 50,000 to 60,000 Da. These results demonstrate that the serum from all domestic species tested contains a specific GH-binding moiety and that under the conditions described here human GH is a more efficient ligand than the homologous hormone.

Animals

Production of anti-idiotypic antisera to rat GH antibodies capable of binding to GH receptors and increasing body weight gain in hypophysectomized rats.

Anti-idiotypic antibodies to rat GH antibodies were produced in both sheep and mice and shown to be capable of mimicking GH by inhibiting 125I-labelled ovine GH (oGH) binding to sheep liver membranes. The sheep anti-idiotypes were characterized further and shown to (1) inhibit 125I-labelled oGH binding to oGH antibodies, (2) inhibit 125I-labelled oGH binding to rat adipocytes and (3) be incapable of inhibiting the binding of either 125I-labelled ovine prolactin or 125I-labelled bovine insulin to sheep liver membranes. This indicated that the antibodies were not limited to certain species or tissues, but were hormone specific. Finally, these anti-idiotypic antibodies were also capable of stimulating an increase in body weight gain in hypophysectomized rats, suggesting that they may be functional as well as structural mimics of GH, although the increased body weight gain was not accompanied by any increase in circulating concentrations of insulin-like growth factor-I.

Animals

Cardiovascular reactivity and interpersonal influence: active coping in a social context.

Previous studies have demonstrated that effortful attempts to secure positive outcomes or avoid negative outcomes produce significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Although these effects of active coping on cardiovascular reactivity are central in current psychosomatic theories, virtually all of the research to date has used impersonal, asocial tasks. Our two studies examined the cardiovascular effects of effortful attempts to influence other people. In Study 1, male subjects attempting to influence the opinions of their discussion partner to improve their own chances of winning money displayed significantly greater SBP, DBP, and HR reactivity. In Study 2, we obtained similar effects on SBP and DBP reactivity in men and women, while both preparing an influence attempt and making that attempt. Furthermore, reactivity levels were larger as the magnitude of incentive for successful persuasion increased. Implications of this interpersonal equivalent of active coping for the development of cardiovascular disease are discussed.

Blood Pressure

Computer-aided design and physiological testing of a luteinising hormone-releasing hormone analogue for 'adjuvant-free' immunocastration.

An analogue of LHRH containing an extension of Gly-Cys at the carboxyl-terminus has been designed to permit reproducible coupling to a suitably modified carrier via a thioether bond. Potential energy calculations indicated that this analogue adopted a conformation in solution virtually identical to the type II' turn around Gly-6-Leu-7 predicted for native LHRH. Intradermal administration of a conjugate of this analogue with purified protein derivative of tuberculin to male rats previously primed with BCG vaccine rapidly led to complete testicular regression. This adjuvant-free immunisation protocol may represent an alternative to castration for the veterinary control of reproductive function.

Animals

The effect of La(SSB) on PWM-induced immunoglobulin synthesis by anti-La(SSB) positive SLE patients and healthy controls.

The effect of affinity purified La(SSB) on immunoglobulin synthesis in vitro by mononuclear cells (MNC) from anti-La(SSB)-positive systemic lupus erythematosus (SLE) patients and healthy controls was studied. La(SSB) was prepared from calf thymus extract and characterized by SDS-polyacrylamide gel electrophoresis and immunoblotting. Silver staining of gels reveals nine major bands at 68 kD, 43-48 kD and 30-33 kD, of which six were recognized on immunoblots by sera from anti-La(SSB) positive SLE patients. Studies in vitro showed that La(SSB) alone did not stimulate total IgG or IgM synthesis in controls or SLE patients. Low concentrations of La(SSB) (optimal dose less than 0.02 ng/ml) suppressed pokeweed mitogen (PWM)-driven IgG synthesis by controls but not by anti-La(SSB) positive SLE patients. IgM responses were unaffected. Anti-La(SSB) and anti-DNA were detected in PWM-stimulated cultures from both study groups. In the presence of La(SSB) IgM anti-La(SSB) synthesis was enhanced in anti-La(SSB)-positive patients in a dose-dependent manner. In contrast, La(SSB) inhibited anti-La(SSB) production by controls (maximal at 2 ng/ml). La(SSB) had no effect on anti-DNA production in either group. Pre-incubation of control or anti-La(SSB)-positive SLE MNC with La(SSB) before addition to autologous PWM-driven cultures did not induce suppressor cells, although pre-incubation with Concanavalin A (ConA) did. Thus we suggest that La(SSB)-induced suppression of IgG synthesis in PWM-driven control cultures may not be due to induction of regulator cells, possibly missing from SLE cultures, but perhaps is a direct effect on B cells.

Adult

Adjuvant-free immunological manipulation of livestock.

Mice and sheep were immunised to growth hormone release inhibiting hormone (GHRIH) using a number of systems which avoided conventional adjuvants. GHRIH was linked directly, or via a horse IgG carrier, to algin or purified protein derivative of tuberculin. A conjugate of GHRIH and flagella from Salmonella dublin was also prepared. Complexes were administered with or without lipopolysaccharide from S typhosa 0901 in a two-injection schedule. Animals receiving conjugates containing purified protein derivative or flagella were preimmunised with live Bacille Calmette-Guérin (BCG) or live S dublin vaccines respectively. Antibody titres to GHRIH, horse IgG and flagella were determined by radioimmunoassay. The system based on tuberculin yielded anti-GHRIH titres in both species which were equivalent to those obtained using Freund's complete adjuvant, while the system based on S dublin produced similar results but only in mice. These data suggest that carrier proteins of bacterial origin may be useful in the development of adjuvant-free autoimmunisation schedules for the practical manipulation of endocrine systems.

Alginates

Comparison of the immunogenic effects of covalent-bonded immune complexes in mice and sheep.

Covalent antigen-antibody complexes containing the protein antigen ovo-transferrin primed both mice and sheep to give an enhanced antibody response to a subsequent single injection of soluble ovo-transferrin. Complexes prepared using horse, sheep or rabbit antibody had a priming effect in mice, although rabbit antibody-antigen complexes were the most effective. In sheep, only rabbit antibody-antigen complexes significantly enhanced antibody levels.

Adjuvants, Immunologic