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K Lövgren

Publications and source records attributed to K Lövgren.

36 records · Page 2Linked to original sources

Influenza virus ISCOMs: biochemical characterization.

Immunostimulating complexes (ISCOMs) have been prepared from influenza A virus envelope glycoproteins, i.e. haemagglutinin (HA) and neuraminidase (NA). An ISCOM consists of a matrix, which is the micellar form of the glycoside, Quil A, in hydrophobic interaction with both the envelope glycoproteins (HA/NA). The Quil A bound to the ISCOM amounted to 50 micrograms mg-1 (5%) of ISCOM protein. ISCOMs were morphologically identified as symmetrical cage-like structures of approximately equal to 40 nm in diameter with hexagonal or pentagonal subunits of approximately equal to 12 nm. The sedimentation coefficient was approximately equal to 19 S as compared to 30 S for the glycoprotein micelles. The biological activities of the HA and NA are preserved in both ISCOMs and micelles.

Adjuvants, Immunologic↗

Influenza virus ISCOMs: antibody response in animals.

A monovalent experimental ISCOM vaccine has been prepared with the envelope glycoproteins haemagglutinin and neuraminidase of the equine virus strain A/Solvalla/79 (H3N8). In vaccination trials on BALB/c mice the ISCOM vaccine induced more than ten times higher serum antibody titres measured in ELISA than a corresponding experimental micelle vaccine. Similarly, in guinea-pigs the ISCOMs induced about tenfold higher haemagglutination inhibition (HI) and neuraminidase inhibition (NI) titres than a micelle vaccine or a conventional killed influenza whole virus vaccine. Horses vaccinated with a divalent experimental ISCOM vaccine, containing the equine strains A/Prague/56 (H7N7) and A/Solvalla/79 (H3N8), responded with ELISA antibody titres against haemagglutinin which were higher and lasted considerably longer than those in horses vaccinated with conventional whole virus vaccine. ISCOMs induced complete immunoprotection in mice vaccinated with a dose of 1 microgram envelope glycoproteins of the mouse pathogenic strain A/PR/8/34 (H1N1).

Adjuvants, Immunologic↗

Separation of hemagglutinin and neuraminidase from influenza virus membrane by column displacement electrophoresis (isotachophoresis) with preservation of their activities.

Triton X-100-solubilized membrane glycoproteins (neuraminidase and hemagglutinin) from purified equine influenza virus particles were separated by column displacement electrophoresis (isotachophoresis) in the presence of Pharmalyte spacers. Electrophoresis was performed in a 1.80 cm glass electrophoresis column with Sephadex G-25 Fine serving as supporting medium. Triton X-100 was present in the system to suppress protein aggregation. Neuraminidase and hemagglutinin activities were preserved and appeared in the electropherogram as separate peaks with some overlapping.

Cell Membrane↗

The serum antibody response distributed in subclasses and isotypes after intranasal and subcutaneous immunization with influenza virus immunostimulating complexes.

Immunostimulating complexes (iscoms) were prepared from influenza virus glycoproteins (A/PR8(H1N1]. Mice were inoculated with iscoms by local (oral or intranasal) as well as by subcutaneous administration. It was shown that one subcutaneous or intranasal inoculation induced serum antibody responses of similar magnitude. The intranasal administration, however, induced somewhat higher IgA and IgM titres than that induced subcutaneously. After a second intranasal or subcutaneous inoculation a prominent increase of the IgG isotypes was found. The secondary IgA and IgM responses were of similar magnitude as those induced after the primary inoculation. The antibody responses induced were evenly distributed within the IgG isotypes, although the highest titres recorded were of the IgG1 and IgG2 isotypes.

Adjuvants, Immunologic↗

The requirement of lipids for the formation of immunostimulating complexes (iscoms).

The iscom--immunostimulating complex--is a highly immunogenic formulation of microbial membrane antigens. The biochemically analyzed components of the iscom are the protein and the glycoside Quil A. Continued analysis of the iscom showed that the protein moiety--the antigen--does not contribute to the iscom as a construct. Instead, cholesterol and Quil A are the essential structural components assembled together into a typical cage-like structure. A more "fluid" lipid, such as phosphatidylcholine, is needed to facilitate the incorporation of amphipathic poly- or oligopeptides into the iscom matrix.

1,2-Dipalmitoylphosphatidylcholine↗

Antigenic presentation of small molecules and peptides conjugated to a preformed iscom as carrier.

The aim of the present study was to elaborate a carrier system for haptens and synthetic peptides, making them immunogenic without addition of Freund's adjuvants. As carriers, preformed iscoms and micelles as well as BSA have been compared. The iscoms and micelles were prepared with envelope proteins of an influenza virus. As a model hapten, the small molecules of biotin were coupled to iscoms to determine the optimum epitope density for induction of an enhanced antibody response to the hapten. The most efficient carrier tested was the preformed iscom at an epitope density of ten biotin molecules per viral protein in the iscom. This carrier system exceeded the efficacy of both the preformed micelles and BSA, the latter with or without addition of Freund's adjuvant. A favourable epitope density could not be achieved when each of two different synthetic peptides was conjugated to iscoms. Epitope densities higher than one to three peptide molecules per protein lead to polymerization of either the peptide or the carrier. The coupling agent was glutardialdehyde.

Adjuvants, Immunologic↗

Serological responses in Sarcocystis cruzi infected calves challenged with Toxoplasma gondii.

Three four-week-old calves were used in a study on serological responses in combined Sarcocystis cruzi and Toxoplasma gondii infections. One calf (C1) was inoculated orally with 100,000 S cruzi sporocysts, another (C2) with 40,000 sporocysts, while the third (C3) acted as uninfected control. One hundred and five days later, all three calves were inoculated orally with 100,000 T gondii oocysts. The antibody responses to sarcocystis and toxoplasma during 210 days were recorded, using different serological assays. During the S cruzi monoinfection phase, positive antibody reactions were recorded in C1 and C2, using an ELISA with soluble (cytoplasmic) T gondii tachyzoite antigen, while antibody reactions remained negative in the toxoplasma indirect fluorescent antibody test and in an ELISA employing T gondii tachyzoite cell membrane antigen. However, the Sabin Feldman dye test also showed transient low positive titres for C1 and C2 at around day 39 after S cruzi inoculation. When using an ELISA employing soluble S fusiformis cystozoite antigen, increased sarcocystis antibody counts were recorded for C1 and C2 starting two weeks after T gondii inoculation. Otherwise the three calves reacted as expected regarding the general antibody responses to the S cruzi and T gondii infections.

Animals↗

Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients.

127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.

Acyclovir↗

Adrenoceptor blocking agents. Compounds related to metoprolol.

A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regardless of the distance between the aromatic nucleus and the ethanolamine moiety. An ethereal oxygen may be of importance for the affinity to the receptor but this oxygen may not necessarily have to be located as an OCH2 group between the aromatic ring and the ethanolamine chain of the beta-blocker molecule.

Adrenergic beta-Antagonists↗

Adrenergic receptor agonists. Benzofuranylethanolamines.

Two hydroxy-substituted benzofuranylethanolamines (9 and 10), analogues of adrenoceptor-active aryloxypropanolamines, were prepared and their beta-adrenoceptor activity was examined. Compound 9 was found to be a beta 1-selective adrenergic agonist with high intrinsic activity. Due to the rigidity of the benzofuranyl moiety of 9, its functional groups cannot be brought into the same spatial positions as those of a phenylethanolamine-type agonist like isoprenaline. This could indicate that adrenergic agonists of the aryloxypropanolamine type and of the phenylethanolamine type are differently bound to the receptor when eliciting the effect.

Adrenergic beta-Agonists↗

Trial of a novel experimental Toxoplasma iscom vaccine in pregnant sheep.

Fifteen vaccinated ewes (group 1) and 13 unvaccinated ewes (group 2) were each challenged orally with 2000 sporulated Toxoplasma gondii oocysts at 91 (+/- 1) days' gestation. Another four pregnant ewes acted as unvaccinated unchallenged controls. Lamb mortality in group 1 was 36.4% after a mean gestation of 141 days while in group 2 it was 64.7% after a mean gestation of 131.5 days. These differences were not statistically significant. However, substantially more specific antibody was detected in precolostral sera from live lambs from vaccinated ewes than in live lambs from unvaccinated ewes in group 2.

Adjuvants, Immunologic↗