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Biomedical subjects

R J Phillpotts

Publications and source records attributed to R J Phillpotts.

At least 37 records · Page 2Linked to original sources
PubMed1991

Biochemical characterization of herpes simplex virus type-1-immunostimulating complexes (ISCMOs): a multi-glycoprotein structure.

The preparation and characterization of an immunostimulating complex (ISCOM) preparation containing several HSV-1 glycoproteins, including the major glycoproteins B and D is described. The multi-glycoprotein HSV-1 ISCOM preparation was obtained from a gradient-purified aqueous HSV-1 antigen preparation following extraction from infected cells using a zwitterionic detergent. With polyclonal and monoclonal antibodies to HSV-1 glycoproteins in enzyme-linked immunosorbent assay, SDS-polyacrylamide gel electrophoresis and radioimmunoprecipitation techniques, the HSV-1 ISCOM preparation was shown to contain glycoproteins B, C, D, E, H and I, although further, additional proteins were also present. The DNA content of HSV-1 ISCOMs was determined using a 3H-thymidine labelling method. The protein and DNA contents of the HSV-1 ISCOM preparation are discussed with reference to the potentialities of the preparation as a vaccine for use in human beings.

DNA, Viral↗
PubMed1991

Efficacy of HSV-1 ISCOM vaccine in the guinea-pig model of HSV-2 infection.

The capability of a herpes simplex virus (HSV)-1 ISCOM vaccine to protect against intravaginal HSV-2 challenge infection in guinea-pigs is described. The protective efficacy of the HSV-1 ISCOM vaccine is compared with that of a purified, aqueous HSV-1 antigen preparation administered using a similar immunization schedule. The results show that female guinea-pigs immunized with two doses of HSV-1 ISCOM vaccine, each consisting of 20 micrograms of protein given 2 weeks apart responded with high ELISA and neutralization antibody titres, and are almost completely protected against the clinical effects of intravaginal challenge with 10(5.2) TCID50 of HSV-2. This cross-protection is significantly greater than that observed in guinea-pigs immunized with a single dose of HSV-1 ISCOM vaccine, two doses of aqueous HSV-1 antigen preparation or two doses of a mock ISCOM vaccine. However, none of the vaccine preparations completely prevented HSV-2 replication following challenge. Western blot and radioimmunoprecipitation of sera from immunized guinea-pigs show the HSV-1 ISCOM vaccine preparation to contain the major HSV-1 glycoproteins. These findings are discussed in relation to the value and potential use of HSV-1 ISCOM vaccine in humans.

Animals↗
PubMed1989

Protection and serum antibody responses in guinea-pigs and mice immunized with HSV-1 antigen preparations obtained using different detergents.

Guinea-pigs immunized with a zwitterionic detergent-extracted HSV-1 antigen preparation responded with EIA and NT serum antibody titres that were significantly greater than those elicited by a non-ionic detergent-extracted antigen preparation inoculated using a similar dosage schedule. Following intravaginal challenge of the guinea-pigs with HSV-2 (strain SH/B), there was no statistically significant difference in the protection afforded to these animals by the two antigen preparations, although the results indicated the zwitterionic detergent-extracted HSV-1 antigen preparation to be slightly superior in this respect. In mice, the zwitterionic detergent-extracted HSV-1 antigen preparation elicited an EIA antibody response and partial protection against homologous virus challenge. The relevance of these animal models to determination of immunogenicity and efficacy of HSV vaccines prepared for use in man, and the reasons for the differences in immunogenicity of these HSV-1 antigen preparations in guinea-pigs, are discussed.

Animals↗
PubMed1988

A test for the relative potency of herpes simplex virus vaccines based upon the female guinea-pig model of HSV 2 genital infection.

An ELISA for total herpes simplex virus (HSV) 1 antigen content and a test of immunogenicity based upon the female guinea-pig model of HSV 2 genital infection were applied to two samples from batches of HSV 1 subunit ('Skinner') vaccine. The ELISA was reproducible within an approximately threefold limit of error and batches 1 and 2 were indistinguishable in antigen content. The effects of vaccination in the guinea-pig model were assessed by a statistical analysis of scores derived from the principal clinical signs, vaginal oedema and lesions on the external genitalia. The statistical power of the guinea-pig assay was such that reductions in the severity of illness approaching 40% would be significant (P less than 0.05) on 90% of occasions. The ability to make quantitative estimates of immunogenicity will prove useful in the quality control of HSV vaccine batches which are destined for clinical trials in man.

Animals↗
PubMed1988

Vaccine induced HSV 1 antibodies fail to correlate with protection against HSV 2 in guinea pigs.

Guinea pigs immunised with HSV 1 subunit vaccine were bled, and subsequently challenged intravaginally with HSV 2. The clinical response to virus challenge was quantified, and correlations were sought between clinical score and virus-specific serum antibody titre in functional and binding assays (ELISA, neutralization, complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity). No significant relationships were found, and it was concluded that reactivity in the serological assays chosen did not correlate with protection against HSV 2 genital infection in vaccinated female guinea pigs.

Animals↗
PubMed1987

Passive immunization of mice with monoclonal antibodies raised against tick-borne encephalitis virus. Brief report.

Adult Balb/c mice were passively immunized with monoclonal antibodies (100 micrograms/mouse) raised against tick-borne encephalitis (TBE) virus then challenged 24 hours later s.c. with 10 LD50 of TBE virus (Nëudorfl isolate). None of the mice showed evidence of premature death although all except one of the monoclonal antibodies tested are capable of enhancing the infectivity of TBE virus in the Fc receptor-bearing mouse macrophage-like cell line P 388 D 1. The ability of monoclonal antibodies to neutralize TBE virus in vitro, and to fix complement was examined, and of these properties only a single monoclonal antibody, which was able to neutralize virus, was also able to protect mice against virus challenge.

Animals↗
PubMed1985

Rhinovirus colds.

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Benzimidazoles↗
PubMed1985

Antibody-dependent enhancement of tick-borne encephalitis virus infectivity.

Fourteen mouse monoclonal antibodies raised against tick-borne encephalitis virus (TBEV) and polyclonal antisera raised against six other flaviviruses, Edge Hill (EHV), Japanese encephalitis (JEV), Langat (LGTV), louping ill (LIV), West Nile (WNV) and yellow fever (YFV), were tested for their ability to enhance the replication of TBEV in cells of the mouse macrophage-like line P388 D1, and for their reactivity in ELISA and haemagglutination inhibition (HI) tests. Irrespective of their specificity for either the 51K or 58K polypeptide present in TBEV-infected cells, 13 of the 14 monoclonal antibodies enhanced the replication of TBEV but not of WNV. The remaining monoclonal antibody, which immunoprecipitated the 58K polypeptide of TBEV enhanced WNV but not TBEV, although it reacted strongly with both viruses in ELISA and HI tests. Only polyclonal antisera against viruses within the tick-borne encephalitis virus complex (TBEV, LGTV and LIV) enhanced TBEV replication, although all the polyclonal antisera reacted with TBEV by ELISA; two (against JEV and WNV) also reacted by HI test and all enhanced the replication of WNV. These findings suggest that with TBEV, enhancement may be TBEV complex-specific rather than flavivirus-specific. Data derived from testing both polyclonal and monoclonal antibodies suggest further that not all antibodies that bind to the envelope glycoprotein of TBEV are able to enhance the replication of TBEV, and that enhancement is epitope-specific.

Animals↗
PubMed1985

Studies on 44 081 R.P., a new antirhinovirus compound, in cell cultures and in volunteers.

A synthetic compound, 2-[(1,5,10,10a-tetrahydro-3H-thiazolo[3,4b]isoquinolin-3-ylidene) amino]-4-thiazoleacetic acid (S), 44 081 R.P., inhibits the multiplication of rhinoviruses in cell cultures. Of the 69 rhinovirus strains and serotypes that have been studied, 39% were inhibited at a concentration of 7 micrograms/ml, far below that which affects cellular metabolism (250 micrograms/ml). Preliminary data indicate that the compound inhibits some early events of virus replication but that some cellular functions are also involved in its mechanism of action. Despite its antiviral activity in vitro, the compound, when self-administered intranasally as a 0.2% solution to volunteers from the day before to 5 days after inoculation with a human rhinovirus strain, had no significant effect on rhinorrhea, clinical score, or laboratory evidence of infection.

Adolescent↗
PubMed1984

Some further studies on the prediction of experimental colds in volunteers by psychological factors.

An analysis of the incidence of colds in volunteers, exposed experimentally to various rhinovirus and influenza virus challenges, confirmed an earlier report that assessments of virus shedding show a higher degree of infection by rhinovirus in Introverts than they do in Extroverts. The influenza trials however did not show such an effect. In addition, people with higher scores on a widely used self-report inventory of mild psychoneurotic symptoms tended to show more evidence of increased nasal secretion after infection by either type of virus. The specific scale showing the latter effect most clearly was that of Obsessional Symptoms. Taking account of these psychological factors greatly increased the sensitivity of a study of the beneficial effects of interferon.

Antibodies, Viral↗
PubMed1984

Pharmacokinetics of intranasally applied medication during a cold.

The rate at which interferon is cleared from the nose after local administration was measured in volunteers both before and after challenge with virulent strains of human rhinovirus. Interferon was not cleared more rapidly after virus challenge, and there was no relationship between the amount of nasal secretion produced after challenge, and the rate of interferon clearance. These findings suggest that an inverse relationship between the quantity of a locally applied antirhinovirus drug which is recovered in nasal wash, and clinical and laboratory evidence of rhinovirus infection may be taken as evidence for a beneficial effect of the drug.

Administration, Intranasal↗
PubMed1984

Intranasal lymphoblastoid interferon ("Wellferon") prophylaxis against rhinovirus and influenza virus in volunteers.

Purified lymphoblastoid interferon (HuIFN-alpha) or placebo was self-administered intranasally by volunteers using a spray device three times daily for four and one-third days beginning one day before virus challenge. Each subject received a total dose of 35.1 Mu of interferon (IFN) administered in 13 equal doses of 2.7 Mu. Doses were administered in a volume of 0.2 ml (0.1 ml to each nostril). The first group received human rhinoviruses types 9 and 14. There were no significant colds in 19 volunteers receiving IFN and 7 in 23 volunteers receiving placebo (p less than 0.05). Serological responses and/or recovery of challenge virus were obtained in 14 (74%) recipients of IFN and in all 23 recipients of placebo (p less than 0.05). Mean daily and total clinical scores and mean daily and total nasal secretion weights were significantly greater in those receiving placebo than in those given IFN. The second group received influenza virus A/Eng/40/83. There were 4 significant illnesses in 13 volunteers receiving IFN and 10 in 17 volunteers receiving placebo (p greater than 0.05). Serological responses and/or recovery of challenge virus were obtained in 11 volunteers receiving IFN and 14 volunteers receiving placebo. Mean daily secretion weight and mean clinical scores were lower in those given IFN than in those given placebo - the differences were significant for clinical score on 2 days. The results suggest that IFN prophylaxis was less effective against influenza A than against rhinovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Evaluation of the antirhinovirus chalcone Ro 09-0415 given orally to volunteers.

Ro 09-0415, a phosphorylated 'pro-drug' of the potent antirhinovirus compound, 4' ethoxy-2'-hydroxy-4, 6' dimethoxy-chalcone (Ro 09-0410) was tested in a double-blind placebo-controlled trial for its protective effect against experimental rhinovirus infection. The maximum dose, 1200 mg bd, based on considerations of practicality and tolerance was given orally both before and after challenge with a sensitive rhinovirus, type 9. Plasma concentrations of active compound in excess of those required for the inhibition of rhinovirus type 9 in vitro were achieved, but there was no evidence to suggest that treatment with Ro 09-0415 had a beneficial effect. It is concluded that Ro 09-0415 given orally is unlikely to be of value in the prophylaxis or therapy of human rhinovirus infection.

Administration, Oral↗
PubMed1983

Failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

Adolescent↗
PubMed1983

An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-alpha 2.

Before the prophylactic effect of human interferon alpha 2 (HuIFN-alpha 2) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.

Administration, Intranasal↗
PubMed1983

Therapeutic activity of enviroxime against rhinovirus infection in volunteers.

The therapeutic effect of intranasal 2-amino-1-(isopropylsulphonyl)-6-benzimidazole phenyl ketone oxime (enviroxime) against human rhinovirus type 9 was evaluated in a double-blind, placebo-controlled volunteer trial. Enviroxime given 6 times a day was well tolerated, producing a reduction in clinical evidence of infection which coincided with the start of medication (44 h after virus challenge). Although there was a statistically significant reduction in clinical score in the enviroxime group on day 5 after virus challenge, reductions in total clinical score accumulated during the trial and reductions in the quantity of nasal secretions were not significant. A separate analysis was performed on data from volunteers who did not have symptoms when medication began (and who might have been expected to benefit more from enviroxime therapy). No apparent enhancement of the effects of enviroxime could be demonstrated in this group.

Adult↗