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Antibody-inducing properties of a prototype bivalent herpes simplex virus/enterotoxigenic Escherichia coli DNA vaccine.

The antibody-inducing properties of a bacterial/viral bivalent DNA vaccine (pRECFA), expressing a peptide composed of N- and C-terminal amino acid sequences of the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) fused with an inner segment encoding the major structural subunit of enterotoxigenic Escherichia coli (ETEC) CFA/I fimbriae (CFA/I), was evaluated in BALB/c mice following intramuscular immunization. The bivalent pRECFA vaccine elicited serum antibody responses, belonging mainly to the IgG2a subclass, against both CFA/I and HSV gD proteins. pRECFA-elicited antibody responses cross-reacted with homologous and heterologous ETEC fimbrial antigens as well as with type 1 and type 2 HSV gD proteins, which could bind and inactivate intact HSV-2 particles. On the other hand, CFA/I-specific antibodies could bind but did not neutralize the adhesive functions of the bacterial CFA/I fimbriae. In spite of the functional restriction of the antibodies targeting the bacterial antigen, the present evidence suggests that fusion of heterologous peptides to the HSV gD protein represents an alternative for the design of bivalent DNA vaccines able to elicit serum antibody responses.

Animals↗

Reactivity and immunogenicity of bivalent (AC) and tetravalent (ACW135Y) meningococcal vaccines containing O-acetyl-negative or O-acetyl-positive group C polysaccharide.

The immunogenicity and the reactivity of two bivalent (AC) and two tetravalent (ACW135Y) meningococcal vaccines containing either the O-acetyl-positive or the O-acetyl-negative group C polysaccharide were compared in healthy adolescent and adult volunteers. The vaccines contained high-molecular-weight, purified capsular meningococcal polysaccharides and were administered subcutaneously at a dose of 50 micrograms for each polysaccharide. Reactivity was low for all vaccines, and the tetravalent vaccines were not significantly more reactive than the bivalent vaccines. Immunogenicity was measured by assay of bactericidal antibodies in pre- and postvaccination sera. More than 90% of the vaccines had at least a fourfold increase in the bactericidal antibody titer against each group of meningococcus represented in the vaccines. Addition of polysaccharide W135 and polysaccharide Y to polysaccharides A and C did not alter the immunogenicity of the latter polysaccharides. Thus, there is no evidence of antigenic competition with the tetravalent vaccine. Comparison of the antibody response to the O-acetyl-positive and the O-acetyl-negative variants of group C polysaccharide in the bivalent vaccines, as measured by both bactericidal and enzyme-linked immunosorbent assays, indicates that in adults, the two types of group C polysaccharide are similarly immunogenic.

Adolescent↗

Development of a cAdVax-based bivalent ebola virus vaccine that induces immune responses against both the Sudan and Zaire species of Ebola virus.

Ebola virus (EBOV) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. While lethal human outbreaks have so far been restricted to sub-Saharan Africa, the potential exploitation of EBOV as a biological weapon cannot be ignored. Two species of EBOV, Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV), have been responsible for all of the deadly human outbreaks resulting from this virus. Therefore, it is important to develop a vaccine that can prevent infection by both lethal species. Here, we describe the bivalent cAdVaxE(GPs/z) vaccine, which includes the SEBOV glycoprotein (GP) and ZEBOV GP genes together in a single complex adenovirus-based vaccine (cAdVax) vector. Vaccination of mice with the bivalent cAdVaxE(GPs/z) vaccine led to efficient induction of EBOV-specific antibody and cell-mediated immune responses to both species of EBOV. In addition, the cAdVax technology demonstrated induction of a 100% protective immune response in mice, as all vaccinated C57BL/6 and BALB/c mice survived challenge with a lethal dose of ZEBOV (30,000 times the 50% lethal dose). This study demonstrates the potential efficacy of a bivalent EBOV vaccine based on a cAdVax vaccine vector design.

Adenoviridae↗

Compatibility of a bivalent modified-live vaccine against Bordetella bronchiseptica and CPiV, and a trivalent modified-live vaccine against CPV, CDV and CAV-2.

Eight puppies (group 1) were vaccinated once with a bivalent modified-live vaccine against infectious tracheobronchitis by the intranasal route and at the same time with an injectable trivalent vaccine against canine parvovirus, canine distemper virus and canine adenovirus; a second group of eight puppies (group 2) was vaccinated only with the intranasal bivalent vaccine, and a further eight puppies (group 3) were vaccinated only with the injectable trivalent vaccine. Three weeks later they were all challenged with wildtype Bordetella bronchiseptica and canine parainfluenza virus by the aerosol route, and their antibody responses to the five vaccine organisms were determined. Oronasal swabs were taken regularly before and after the challenge for the isolation of bacteria and viruses, and the puppies were observed for clinical signs for three weeks after the challenge. There were no significant differences in the puppies' titres against canine parvovirus, canine distemper virus and canine adenovirus type 2 between the groups vaccinated with or without the bivalent intranasal vaccine. After the challenge the mean clinical scores of the two groups vaccinated with the intranasal vaccine were nearly 90 per cent lower (P=0.001) than the mean score of the group vaccinated with only the trivalent injectable vaccine, and the puppies in this group all became culture-positive for B bronchiseptica and canine parainfluenza virus. There were only small differences between the rates of isolation of B bronchiseptica from groups 1, 2 and 3, but significantly lower yields of canine parainfluenza virus were isolated from groups 1 and 2 than from group 3.

Adenoviridae Infections↗

Preferential nondisjunction of specific bivalents in oocytes from Djungarian hamsters (Phodopus sungorus) following colchicine treatment.

In an attempt to study the mechanisms leading to nondisjunction during meiosis I, Djungarian hamster females were treated with colchicine (3 mg/kg), which binds specifically to tubulin. The number of ovulated oocytes per female was significantly reduced following colchicine treatment (8.2 +/- 5.3, compared to 10.6 +/- 5.9 in controls receiving saline solution only). Application of colchicine rather late during oocyte maturation (ie, 5.5 h after injection of human chorionic gonadotrophin) caused a significant increase in the number of ovulated diploid (34.5%) and hyperhaploid (11.7%) oocytes, compared to the frequencies observed in the saline-treated controls (0.8% and 3.5%, respectively). Specific bivalents (viz, the large meta- and submetacentric chromosomes of groups A, B, and C) were preferentially involved in colchicine-induced nondisjunction. The same pattern of chromosomal malsegregation was previously observed in oocytes from this hamster species following hypergonadotrophic stimulation. Preferential involvement of bivalents in the process of nondisjunction, whether induced by colchicine or hypergonadotrophic stimulation, is explained by an interference with microtubular function affecting those bivalents that are the last to segregate.

Animals↗

Random acrocentric bivalent associations in human pachytene spermatocytes. Molecular implications in the occurrence of Robertsonian translocations.

Acrocentric bivalent associations were studied in 232 human male germ cells at pachytene in order to understand better the preferential involvement of chromosomes 13, 14, and 21 in Robertsonian translocations. The tendency of each acrocentric bivalent to associate with another was not correlated with NOR activity, as measured by silver staining. Good agreement was noticed between their ability to associate and the amount of satellite DNA in human acrocentric chromosomes. The distribution of two-by-two acrocentric bivalent associations was random. In order to reconcile this result with the nonrandom distribution of Robertsonian translocations, a molecular hypothesis is proposed. The model is based on homology of recombinational sites, interspersed at regular interval in satellite DNA, which could increase the probability of accidental unequal crossing-over between two specific acrocentric chromosomes.

Aged↗

Under what circumstances is the human XY bivalent tangled? A note on chromosomally-derived sterility.

A microspread, early-mid diplotene nucleus of a man with a normal karyotype and presumably normal meiosis is compared with a similar, earlier described nucleus of a man with meiotic arrest, heterozygous for a (14;21) Robertsonian translocation (Rosenmann et al., 1985). The axes of the XY bivalent of normal diplotene have an extremely tangled configuration, whereas those of the meiotically-arrested cell are straight, recalling the shape of the XY which is normally found in early pachytene. The morphological reversal from the complex configuration to a simpler shape may be associated with reactivation of the sex chromosome(s). Such a reactivation may be responsible for the sterility of the carrier of the Robertsonian translocation which thus may be considered as chromosomally-derived. The diplotene cells shown here have autosomal bivalents with continuous axes and various degrees of focal separation as is typical for diplotene in general. The observations on axis continuity, bivalent segmental dilatations, and XY tanglement in diplotene are compared with findings by others in human ultrathin sectioned material.

Humans↗

Human T cells resistant to complement lysis by bivalent antibody can be efficiently lysed by dimers of monovalent antibody.

We have previously shown that bivalent human gamma1 CD3 monoclonal antibody (mAb) is ineffective at mediating lysis of human T cells with human complement. In this paper we have used genetic engineering and sulfur chemistry to prepare 2 types of human gamma1 CD3 mAb dimer, with the aim of improving complement lysis activity. The IgG molecules forming the dimers were linked together at their C-termini by stable bismaleimide thioether bridges. The first dimer was composed of 2 bivalent mAb molecules. This dimer proved incapable of lysing human T-cell blasts with human, rabbit, or guinea pig complement. The second dimer consisted of 2 molecules of a monovalent derivative (possessing a single Fab domain) of the bivalent mAb. This dimer was highly lytic with human complement, with a lytic titer 64-fold greater than that of the nondimerized monovalent mAb. The maximum level of lysis of human T-cell blasts achieved with this monovalent mAb dimer was equal to that obtained with the therapeutic antilymphocyte mAb alemtuzumab, but its lytic titer was 4-fold greater. The monovalent mAb dimer was also found to be lytic in the presence of rabbit and guinea pig complement. Dimerization of monovalent antibodies may provide a general strategy for improving the cytolytic activity of other mAbs that are normally unable to induce lysis with complement. The monovalent CD3 mAb dimer may have potential for development as an agent for immunotherapy of T-cell leukemia.

Antibodies, Monoclonal↗

Differential biological activities between mono- and bivalent fragments of anti-prolactin receptor antibodies.

Previous studies have established that antibodies against PRL receptors can mimic PRL effects on casein gene expression and on thymidine incorporation into DNA in the mammary gland. In the present work, bivalent F(ab')2 and monovalent Fab' fragments of the anti-PRL receptor antibodies were prepared. Both inhibited the binding of 125I-labeled PRL to rabbit mammary gland membranes. F(ab')2 as well as the unmodified antibodies were able to enhance casein synthesis and thymidine incorporation into DNA in cultured rabbit mammary gland explants. Moreover, when added to isolated membranes, both were able to induce the generation of the PRL relay which specifically stimulates caseins gene transcription in isolated mammary nuclei. In contrast, monovalent fragments were totally devoid of any of these PRL-like activities. However, bivalent and monovalent antibodies were equipotent in inducing a down-regulation of PRL receptors in mammary explants. These data indicate that the biological PRL-like activity of antibodies against PRL receptors is strictly related to their bivalent structure. This fact indicates a possible crucial role of a microaggregation of PRL receptors in the transmission of the PRL message across the membranes. In addition, these experiments reinforce the idea that internalization and down-regulation are not directly related to PRL action on casein or DNA synthesis in mammary gland.

Animals↗

Mechanism of biphasic action of mono- and bivalent salts on the binding of prolactin to the receptor in the rabbits mammary gland.

The influence of NaCl, KCl, CaCl2, and MgCl2 on the binding of prolactin (PRL) to its receptor was investigated. The salts were dissolved in a metallic ion-free binding buffer and had biphasic effects on changes in the association rate constant (k+1) of PRL binding, depending on their concentrations: there was an increase in the k+1 at lower concentrations and a decrease at higher concentrations. The dissociation rate of bound PRL was unaffected. NaCl at any concentration did not change the binding capacity. Bivalent salts, at higher than 25 mM, increased the capacity about 1.6-fold as compared to the 0 mM control. By cross-linking the PRL-receptor complex, the band of a molecular weight (Mr) 34,500 receptor could always be detected on the autoradiogram. An Mr 78,000 receptor appeared only after incubation with bivalent salts. Data indicate that the binding of PRL to an Mr 78,000 receptor is directly regulated by bivalent cation.

Animals↗

Bivalent ligands with rigid double-stranded DNA spacers reveal structural constraints on signaling by Fc epsilon RI.

Degranulation of mast cells and basophils during the allergic response is initiated by Ag-induced cross-linking of cell surface IgE-Fc epsilon RI receptor complexes. To investigate how separation distances between cross-linked receptors affect the competency of signal transduction, we synthesized and characterized bivalent dinitrophenyl (DNP)-modified dsDNA oligomers with rigid spacing lengths of approximately 40-100 A. All of these bivalent ligands effectively bind and cross-link anti-DNP IgE with similar affinities in the nanomolar range. The 13-mer (dsDNA length of 44 A), 15-mer (51 A), and flexible 30-mer ligands stimulate similar amounts of cellular degranulation, about one-third of that with multivalent Ag, whereas the 20-mer (68 A) ligand is less effective and the rigid 30-mer (102 A) ligand is ineffective. Surprisingly, all stimulate tyrosine phosphorylation of Fc epsilon RI beta, Syk, and linker for activation of T cells to similar extents as multivalent Ag at optimal ligand concentrations. The magnitudes of Ca(2+) responses stimulated by these bivalent DNP-dsDNA ligands are small, implicating activation of Ca(2+) mobilization by stimulated tyrosine phosphorylation as a limiting process. The results indicate that structural constraints on cross-linked IgE-Fc epsilon RI complexes imposed by these rigid DNP-dsDNA ligands prevent robust activation of signaling immediately downstream of early tyrosine phosphorylation events. To account for these results, we propose that activation of a key downstream target is limited by the spacing between cross-linked, phosphorylated receptors and their associated components.

2,4-Dinitrophenol↗

Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2.

We have generated a stable bivalent Fv molecule [(dsFv)2] of the anti-erbB2 monoclonal antibody e23 in which the V(H) and V(L) domains of the Fv are linked to each other by a disulfide bond and the two Fvs are connected by a 15-amino acid linker (T. K. Bera et al., J. Mol. Biol., 281: 475-483, 1998). The e23 (dsFv)2 molecule is linked to a truncated form of Pseudomonas exotoxin (PE38) to generate a bivalent disulfide-stabilized immunotoxin e23 (dsFv)2-PE38. Compared to the monovalent immunotoxin, the (dsFv)2 immunotoxin showed greatly increased cytotoxicity to four cancer cell lines expressing low levels of erbB2 but not to four other cell lines with high erbB2 expression. e23 (dsFv)2-PE38 was administered i.v. to mice, and its half-life was determined. The t(1/2)alpha and t(1/2)beta were 20 and 325 min, respectively, whereas the corresponding values for the monovalent dsFv immunotoxin were shorter, 6 and 52 min. The antitumor activities of the monovalent and bivalent immunotoxin were compared using mice bearing A431 tumors. Despite the fact that e23 (dsFv)2-PE38 was 13-fold more active than e23 dsFv-PE38 on A431 cells in cell culture, its antitumor activity in mice was <2-fold that of the monovalent immunotoxin. These data show that a large increase in avidity does not always lead to an increase in cytotoxic activity. Furthermore, in one of the cases in which cytotoxic activity in vitro was greatly enhanced, there was only a small increase in antitumor activity.

Animals↗

Pretargeting of renal cell carcinoma: improved tumor targeting with a bivalent chelate.

Radiolabeled monoclonal antibodies (mAbs) can target tumors selectively. Sustained activity levels in nontarget tissues limit their application. Pretargeting approaches using bispecific mAbs (bsmAbs) or the biotinavidin interaction have been proposed to improve tumor:nontumor ratios. Pretargeting a tumor and subsequently administering the radioactivity as a low molecular weight ligand fundamentally changes the pharmacokinetics of the radiolabel. In previous studies, we have shown successful radioimmunotargeting of diethylenetriaminepentaacetic acid (DTPA) labeled with indium-111 to renal cell carcinoma (RCC) after pretargeting in nude mice. In this study, we aimed to optimize further a pretargeting strategy in nude mice with RCC xenografts based on a bispecific anti-RCC x anti-DTPA mAb. Using this two-step approach, we studied whether the use of a bivalent chelate ((111)In-diDTPA) could improve radioimmunotargeting. The (111)In-diDTPA dose greatly affected the uptake of the radiolabeled chelate in the tumor. At a low (111)In-diDTPA dose (< or = 7 pmol), tumor uptake of (111)In-diDTPA was very high [>50% injected dose (ID)/g, 1 h postinjection (p.i.)], whereas at higher doses (> or = 20 pmol), tumor uptake of (111)In-diDTPA decreased (<30% ID/g). With monovalent (111)In-DTPA uptake of the radiolabel in the tumor was much lower (<10% ID/g, 1 h p.i.). Furthermore, the bivalent chelate accreted rapidly in the tumor (78% ID/g, 4 h p.i.) and was virtually completely retained in the tumor during several days p.i. (92% ID/g, 72 h p.i.). Clearance of the (111)In-diDTPA from the blood and kidneys was rapid and complete without the need to clear the bsmAb from the blood, probably due to the relative lability of the univalent bsmAb-diDTPA complexes in the blood. As a result, with this two-step pretargeting approach tumor:blood ratios increased up to values as high as 3500 at 72 h p.i. High doses of diDTPA could be targeted preferentially to the tumor, indicating that this approach could also be used for radioimmunotherapy. Tumors could be imaged up to 1 week p.i. of 50 microCi of (111)In-diDTPA. Quantitative analysis of the images confirmed the biodistribution data and indicated that, at 20 h p.i., 50 +/- 15% of the whole-body activity was localized in the tumor. In conclusion, these studies indicate that the use of bivalent chelates can very effectively optimize two-step targeting of tumors with bsmAbs. Our data indicate that this approach could optimize radioimmunotherapy.

Animals↗

Pretargeted radioimmunotherapy of human colorectal xenografts with bispecific antibody and 131I-labeled bivalent hapten.

UNLABELLED: We have developed a pretargeting strategy, called the affinity enhancement system (AES), which uses bispecific antibodies to target radiolabeled bivalent haptens to tumor cells. The aim of this study was to evaluate the potential of the AES for the radioimmunotherapy (RIT) of LS174T colorectal xenografts in comparison with RIT with directly labeled F(ab')2 fragment. METHODS: A total of 6 groups of tumor-bearing mice were treated using anticarcinoembryonic antigen (CEA) x anti-diethylenetriamine pentaacetic acid (DTPA)-In bispecific antibody (BsF(ab')2) and 131I-labeled di-DTPA-In bivalent hapten. Three groups of mice were injected with various activities of 131I-labeled bivalent hapten (75, 96, and 112 MBq) 20 h after administration of BsF(ab)'2. Three other groups were injected with an almost constant activity of labeled hapten (102 MBq) at 3 time periods (15, 30, and 48 h) after BsF(ab')2 administration. For conventional RIT, mice were treated with 96 MBq 131-labeled anti-CEA F(ab')2. Control groups were left untreated. Toxicity and tumor growth were monitored at weekly intervals. RESULTS: Doses used for conventional RIT induced severe toxicity and resulted in death of several treated animals. Nevertheless, all surviving animals treated with 131I-labeled anti-CEA F(ab')2 relapsed shortly after treatment (tumor growth delay = 48+/-13 d). For animals treated with the AES reagents, toxicity varied with the pretargeting time interval and the administered activity. For 20-h pretargeting time, the maximum tolerated dose was 96 MBq. For all AES RIT except 1 (with 48-h pretargeting time interval and growth delay of 82+/-26 d), no tumor growth was observed over a period of 8 mo. Furthermore, based on clinical and histologic criteria, 33% of the treated mice were considered cured. CONCLUSION: High cure rates of LS174T colon carcinoma were achieved with the AES, and the flexibility of the pretargeting approach allowed the control of hematologic toxicity, which is the main limitation to dose escalation with conventional RIT.

Animals↗

[A bivalent VP1 gene vaccine against Coxsackie virus B1/B3].

OBJECTIVE: To construct a bivalent VP1 gene vaccine against Coxsackie virus B1 and B3 (CVB1 and CVB3) and to test its immunogenicity in mice. METHODS: The VP1 gene of CVB1 was amplified by RT-PCR. The VP1 genes of CVB1 and of CVB3 under the control of cytomegalovirus (CMV) promoter and SV40 promoter respectively were inserted oppositely into the pCR3-Uni, a eukaryotic expression vector. The resultant bivalent gene vaccine plasmid was used to inoculate 3-week-old BALB/c mice. Immunofluorescence test and RT-PCR were conducted 24, 48, and 96 hours after the transfection. Sera of the tested animals were sampled at 0, 2, 4, and 6 weeks after the inoculation and detected for CVB-specific antibodies by ELISA. RESULTS: A bivalent gene vaccine plasmid of CVB1 and CVB3 was obtained. Samples of 4 and 6 weeks after the inoculation were shown to be CVB-antibody positive, while those of 0 and 2 weeks after the inoculation shown negative. CONCLUSION: The gene vaccine thus constructed induces CVB-speicific antibodies in mice, and can serve as gene vaccine candidate for human beings.

Animals↗

Bivalent disulfide-stabilized fragment variable immunotoxin directed against mesotheliomas and ovarian cancer.

We have used protein engineering to generate a stable bivalent fragment variable (Fv) molecule from the antimesothelin antibody SS, in which the VH and VL domains of the Fv are linked to each other by a disulfide bond, and the two Fvs are connected by a flexible 15-amino acid (Gly4-Ser)3 linker. The SS (dsFv)2 molecule is fused to a M(r) 38,000 truncated form of Pseudomonas exotoxin to generate a bivalent, disulfide stabilized, (dsFv)2 immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro, and purified to approximately 95% purity with a high yield of > 10%. Binding studies demonstrated that the (dsFv)2 molecule has 40 times higher apparent affinity for recombinant mesothelin than a monovalent dsFv molecule. The (dsFv)2 immunotoxin was 4-10-fold more cytotoxic to three mesothelin antigen-positive cell lines than the monovalent dsFv immunotoxin. However, when tested in mice bearing tumor cells expressing mesothelin, the antitumor activity of the bivalent immunotoxin is very similar to the activity of the lower affinity monovalent immunotoxin. Our data indicate that increasing affinity of an antibody fragment does not necessarily lead to higher antitumor activity of an immunotoxin in vivo.

ADP Ribose Transferases↗

Pretargeting with labeled bivalent peptides allowing the use of four radionuclides: (111)In, (131)I, (99m)Tc, and (188)Re.

PURPOSE: The therapeutic effect of directly labeled antibodies in solid tumors is limited, mainly due to the relatively low uptake of the radiolabeled antibody in tumors as compared with their blood level. In previous studies, we have shown that renal cell carcinoma (RCC) can be targeted very effectively with the (111)In-labeled bivalent peptide di-diethylenetriamminepentaacetic acid diDTPA-FKYK, after pretargeting the tumor with a bispecific antibody. In this study, we further developed this pretargeting approach for radioimmunotherapy of renal cell cancer. EXPERIMENTAL DESIGN: Pretargeting with the biologically produced anti-RCC x anti-DTPA bispecific monoclonal antibody (bsMAb G250xDTIn1) was tested in mice with SK-RC-52 RCC tumors. Tumors were pretargeted with 15 micro g of bispecific monoclonal antibody G250xDTIn1, and 24 h later, mice received 6 ng of the radiolabeled bivalent peptide. Two different peptides were used: (a) diDTPA-FKYK labeled with (111)In or (131)I; and (b) thiosemicarbonylglyoxylcysteinyl-diDTPA(In)-KYKK labeled with (99m)Tc or (188)Re. Mice were killed 6, 24, 48, and 72 h postinjection (p.i.), and biodistribution of the radiolabel was determined. RESULTS: The (111)In-labeled peptide showed excellent tumor uptake [42.6 +/- 7.3% injected dose/gram (ID/g) at 6 h p.i. and 25.6 +/- 7.7% ID/g at 72 h p.i.] and tumor:blood ratios (700 at 72 h p.i.). The specific tumor targeting of (188)Re- and (99m)Tc-labeled peptides was similar (20-25% ID/g, 6 h p.i.). However, the uptake and the retention in the tumor of the (99m)Tc- and (188)Re-labeled peptide were significantly lower than those of the (111)In-labeled peptide. Tumor uptake of the (131)I-labeled peptide was significantly lower as compared with the other three radiolabeled peptides; furthermore, an almost complete washout of the radiolabel from the tumor over time was observed (14.5 +/- 4.9% ID/g at 6 h p.i. and 0.33 +/- 0.15% ID/g at 72 h p.i.). CONCLUSIONS: Using a newly developed bivalent peptide, this pretargeting approach can now be used for targeting with the matched pair (188)Re and (99m)Tc.

Animals↗

Immunocomb Chlamydia bivalent assay to study Chlamydia species-specific antibodies in patients with coronary heart disease.

BACKGROUND & OBJECTIVE: Serological evidences suggested an association between Chlamydia pneumoniae infection and coronary heart disease (CHD). Efficacy of available serological tests for detection of C. pneumoniae antibody has been debated. The present study was carried-out to assess the efficacy of Immunocomb Chlamydia bivalent IgG assay vis-à-vis micro immunofluorescence (MIF) test in detecting C. pneumoniae and C. trachomatis--specific antibodies in patients with CHD. METHODS: Serum samples collected from clinically confirmed cases of CHD (n=114) were subjected to Immunocomb Chlamydia bivalent assay and the standard MIF test. Antibodies specific to C. pneumoniae and C. trachomatis were detected quantitatively. RESULTS: Though Immunocomb Chlamydia bivalent test yielded 73.7 per cent positivity for C. pneumoniae- specific IgG antibody (compared to 50.8% by MIF), the specificity of Immunocomb was found only 32.14 per cent. Positive and negative predictive values of Immunocomb assay were 54.8 and 60.0 per cent respectively. INTERPRETATION & CONCLUSION: The findings of the present study indicated that though Immunocomb assay was inferior to MIF, it can be used as a method for presumptive serology due to its rapidity and ease of performance. Wherever possible, one or more additional tests should also be performed to increase the specificity of such studies.

Aged↗