Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 55 records · Page 3Linked to original sources

PubMed1994

Protective vaccination against primary and recurrent disease caused by herpes simplex virus (HSV) type 2 using a genetically disabled HSV-1.

The vaccine potential of a mutant herpes simplex virus (HSV) type 1, with a deletion in the glycoprotein H (gH) gene, was evaluated. The virus requires a gH-expressing cell line for multi-cycle growth but can complete a single cycle of infection in noncomplementing cells. Such viruses, termed DISC (disabled infectious single cycle) viruses, should be safe, yet still able to stimulate humoral and cell-mediated responses against a broad range of virus antigens in vaccinated hosts. Prophylactic vaccination of guinea pigs with DISC HSV-1, by ear scarification or direct infection of the vaginal mucosa, afforded a high degree of protection against HSV-2-induced primary genital disease and reduced significantly the frequency of subsequent disease recurrence. There was also a trend toward reduced recurrence following therapeutic vaccination of animals already infected with HSV-2. DISC HSV vaccination, therefore, offers an effective route for control of HSV disease.

Animals↗

PubMed1994

IgG subclass response and protection against challenge following immunisation of mice with various influenza A vaccines.

The serum total IgG and IgG subclass and nasal wash IgA and IgG antibody responses of mice to influenza virus A/Hong Kong/68 (H3N2) subunit preparations administered parenterally as a single dose, incorporated either in immune stimulatory compounds (ISCOMs) or liposomes with Freund's Complete Adjuvant, or as an aqueous material, as well as to live, infectious virus were measured by ELISA at 10 days and 3, 5, 7 and 22 weeks after immunisation. The protection of the upper and lower respiratory tracts provided by these preparations against homologous and heterologous challenge infection was assessed. Of the four variously-presented subunit preparations, influenza subunit ISCOMs induced relatively high and persisting levels of each of the different IgG subclasses, particularly IgG2a, throughout the study, and most nearly approached those observed after intranasal infection of mice with infectious virus. Furthermore, nasal wash IgA and IgG antibody levels, particularly at 5 or 7 weeks after immunisation, were also significantly greater in mice given the subunit ISCOM preparation than those induced by other subunit preparations with adjuvant or subunits given alone, and provided protection of both the upper and lower respiratory tracts against challenge as similar to that elicited by infectious virus.

Animals↗

PubMed1993

Minor recorder imperfections can cause artifacts in the RR interval spectrum derived from Holter recordings.

Spectral analysis of the heartbeat (RR) interval is a powerful tool for noninvasively assessing the autonomic nervous system. In addition, it may prove to be valuable in stratifying patients at risk for cardiac death. The authors report on a case in which spectral analysis of the RR interval exhibited harmonically related peaks within the physiological range that defied physiological explanation. Analysis showed that these peaks resulted from a subtle abnormality of the Holter recorder that was not apparent in the observed electrocardiogram. Since this type of abnormality can be produced by either minor damage or a manufacturing error in any brand of Holter recorder, the RR interval spectrum derived form a Holter electrocardiogram should always be critically examined for this particular artifact.

Artifacts↗

PubMed1993

The subclass IgG responses of mice to influenza surface proteins formulated into liposomes.

Unprimed mice and mice primed by prior infection with an H1N1 subtype of influenza virus were used to assess the total and subclass IgG serum antibody responses to influenza virus A/Sichuan/2/87 (H3N2) surface haemagglutinin and neuraminidase proteins incorporated into four different formulations of liposomes. Only one of these liposome preparations, DSPC(B), induced greater total IgG, and subclass IgG1 and IgG2a antibody levels, in sera from both primed and unprimed mice than the aqueous A/Sichuan surface preparations alone administered at equivalent levels of haemagglutinin protein. The same DSPC(B) liposome formulation of A/Sichuan antigens was also the only preparation found to elicit levels of IgG2b and IgG3 subclass antibodies above baseline values in these animals.

Animals↗

PubMed1993

Immunopotentiation of local and systemic humoral immune responses by ISCOMs, liposomes and FCA: role in protection against influenza A in mice.

The immunogenicity and protective efficacy of an influenza A subunit vaccine preparation administered to mice in an aqueous form, or presented as immunostimulatory complexes (ISCOMs), liposomes or with Freund's complete adjuvant (FCA), were assessed in comparative studies with live infectious virus. Both intranasal and parenteral routes of administration were assessed. An enzyme-linked immunosorbent assay (ELISA) was used to measure nasal wash and serum antibody responses in groups of unprimed mice, while protection was determined by the recovery of homologous influenza virus from mouse nasal washes and lung homogenates following challenge infection by the intranasal route. The results showed that parenteral administration of the influenza antigen preparations induced variable levels of both local and systemic antibodies at weeks 3, 7 and 22 postimmunization. Although the overall greatest levels of antibody and protection were elicited in mice following live virus infection, formulation of influenza surface haemagglutinin (HA) and neuraminidase (NA) proteins into ISCOMs elicited high and persistent antibody responses and provided relatively good protection of the upper and lower respiratory tracts of these animals. The results also show a relatively poor effect of the subunit antigen preparations in promoting humoral immune responses and protection irrespective of the nature of their presentation, when given by the intranasal route.

Adjuvants, Immunologic↗

PubMed1993

Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule.

Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers. In the volunteer groups both vaccines induced very high levels of circulating haemagglutination inhibition antibodies but with different serological specificities. Both NIB-14 and NIB-17 vaccines induced high levels of cross-reactive antibodies capable of reacting with both strains, but only NIB-14 vaccine induced significant levels of strain-specific antibodies capable of reacting exclusively with the homologous strain. Antisera containing only cross-reactive antibodies proved as capable of virus neutralization as antisera containing high levels of strain-specific antibodies. We extended the argument that epidemic strains are antigenically more closely related to tissue culture isolates and established that viruses which differ by only single amino acids at critical points in the HA structure can induce a significantly different immune response when used as inactivated vaccines.

Adolescent↗

PubMed1993

The cohort effect and Helicobacter pylori.

A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalence has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%-41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that H. pylori infection is becoming less frequent and is predominantly acquired in childhood.

Adolescent↗

PubMed1993

The inhibitory effect of spermicidal agents on replication of HSV-2 and HIV-1 in-vitro.

Five spermicides including nonoxynol-9 were assessed under in-vitro conditions, for their inhibitory activity against two viruses capable of spread by sexual intercourse, herpes simplex virus type-2 (HSV-2) and the human immunodeficiency virus type-1. A further eight commercially-available spermicidal preparations containing varying concentrations of either nonoxynol-9 or nonoxynol-11 were also assessed for activity against HSV-2. All spermicides and spermicidal preparations tested showed inhibitory activity against both viruses over periods of time ranging from 30 sec to 5 min. This activity was dependent on the concentration of spermicide to which the viruses were exposed.

Antiviral Agents↗

PubMed1992

The IgA and subclass IgG responses and protection in mice immunised with influenza antigens administered as ISCOMS, with FCA, ALH or as infectious virus.

Comparative studies on the local IgA, and circulating IgG subclass antibody responses of mice to A/Sichuan/2/87 (H3N2) influenza virus surface antigens administered with different carrier or delivery systems by the parenteral route, were carried out. The results obtained were compared with the responses observed following live influenza virus infection, and the protection afforded to these animals by these various preparations determined. Infection with live virus elicited early and high levels of protection against homologous virus challenge and this correlated with both local IgA and circulating IgG2a antibody levels. When incorporated into immunostimulating complexes (ISCOMS), A/Sichuan surface antigens promoted high levels of local IgA and circulating IgG1 antibody, and achieved a more rapid and more solid immunity against homologous virus challenge infection, than that elicited by the same surface antigens administered alone or together with Freund's complete adjuvant or alhydrogel.

Aluminum Hydroxide↗

PubMed1992

Acute and latent infection of mice immunised with HSV-1 ISCOM vaccine.

The effect of immunisation with an HSV-1 antigen preparation (containing at least 6 viral glycoproteins) on primary infection with HSV and the establishment of latency, was assessed in two mouse models (involving either skin or corneal challenge with virus). The vaccine preparation, given either with Freund's complete adjuvant or aluminium hydroxide gel or in the form of immunostimulating complexes (ISCOMS), induced high ELISA antibody responses (highest with HSV as the ISCOM preparation) and low levels of neutralising antibody. In both models, immunisation with the HSV ISCOM preparation significantly reduced the incidence of zosteriform spread of virus and the severity of disease and, in some cases, the incidence of latent infection in sensory ganglia. In the eye model it was possible to show that immunisation with the HSV ISCOMS restricted the establishment of latency almost entirely to the ophthalmic part of the trigeminal ganglion. Protection from establishment of latency correlated with prechallenge antibody levels.

Acute Disease↗

PubMed1992

Liposomes enhance the immunogenicity of reconstituted influenza virus A/PR/8 envelopes and the formation of protective antibody by influenza virus A/Sichuan/87 (H3N2) surface antigen.

Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration-rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used.

Adjuvants, Immunologic↗

PubMed1992

Longitudinal study of Toxoplasma seroprevalence in South Yorkshire.

Serum samples collected from individuals of a wide range of ages in South Yorkshire between 1969 and 1990 provided the basis for a longitudinal seroprevalence survey of Toxoplasma gondii antibodies. Sera numbering 3868 were screened for T. gondii specific antibodies using a commercial latex agglutination test. The resultant temporal series of serological profiles revealed a rise, with age, in seroprevalence, the rate of which showed a decrease through time. A plateau of around 40-50% prevalence was attained by the 41- to 45-year age-class in 1969 which was not approached until the 66- to 70-year class in the 1988-90 data set. This trend for decline in seroprevalence was confirmed by statistical analysis for the age range 21-60 years. These results may be indicative of a decrease in the rate of toxoplasma exposure in this study community over the 20-year period. The survey of 1988-90 provides a base-line profile of present-day seroprevalence in which 11% of individuals in the age range 16-45 years (roughly corresponding to the childbearing age-range) show evidence of past infection. The representative nature of the serum collection and public-health implications of these results are discussed.

Adolescent↗

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↗

PubMed1990

Comparative studies of HSV-1 antigens solubilised from infected cells by using non-ionic or zwitterionic detergents.

HSV-1 antigen preparations solubilised from Vero cells by using either the non-ionic detergent Nonidet P40 or the zwitterionic detergent Empigen BB, and purified on sucrose density gradients or over a sucrose cushion, were tested by ELISA with anti-HSV-1 glycoprotein monoclonal antibodies and by radioimmunoprecipitation (RIP) with polyclonal HSV-1 antiserum. Amongst several proteins detected in these preparations, the four major HSV-1 glycoproteins, gB, gC, gD, and gE, were found to be present. Differences between NP40 or Empigen-solubilised HSV-1 antigen preparations with respect to two of these glycoproteins, gB and gE, were detected by using a small panel of monoclonal antibodies. Comparative studies in mice showed the Empigen-solubilised HSV-1 antigen preparations elicited greater antibody responses and greater protection against lethal HSV-1 challenge infection than the NP40-solubilised preparation.

Animals↗

PubMed1990

Pulmonary vascular resistance in neonatal swine: response to right pulmonary artery occlusion, isoproterenol, and prostaglandin E1.

The pulmonary physiological response of adults to unilateral pulmonary artery (PA) occlusion has been well-characterized as resulting in a decrease in the pulmonary vascular resistance (PVR), in order to maintain the same PA pressure and accommodate the entire cardiac output (CO). We evaluated the response of the neonate to unilateral PA occlusion and how this response is altered by infusions of Isoproterenol (Isuprel) and prostaglandin E1 (PGE1) in the neonatal swine model. Twenty farm piglets (five at 1 day, three at 5 days, seven at 14 days, and five at 60 days as controls) underwent left lateral thoracotomy and measurement of PA and left atrial (LA) pressures, CO, and PVR with the right PA open and occluded. To determine if neonatal PVR could be influenced by a vasodilator (indicating the vascular capacity is not fixed) or by an inotrope (indicating the lung is not maximally recruited) this experiment was then repeated with infusions of PGE1 (a vasodilator) at doses of 0.1, 0.5, and 1.0 micrograms/kg/min and subsequently with Isuprel (an inotrope and vasodilator) at doses of 0.1, 0.5, 1.0 micrograms/kg/min. Control measurements taken without unilateral PA occlusion showed that PVR is high at 1 day of age but progressively decreases to a level 89% lower by 60 days of age. The vascular capacity of the neonatal lung is fixed and responds to unilateral PA occlusion with a dramatic increase in PVR. This response cannot be altered by either a vasodilator (PGE1) or an inotrope (Isuprel) thereby limiting the utility of these drugs in treating neonatal pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

PubMed1990

Surgical wound dressings as barriers to an enveloped virus.

To determine their efficacy as barriers to the passage of lipid-enveloped viruses, wound dressings were exposed to known concentrations of Semliki Forest virus (SFV) at their inner surfaces for varying periods of time. The dressings were tested such that their outer surfaces were maintained in either a dry or a wet environment. Out of a total of 120 dressings each tested at four time points under wet conditions, virus was found to have penetrated on only one occasion. Similarly, virus penetration was noted in only a single test out of 442 carried out on 59 dressings under dry conditions. The dressings under test thus proved highly effective barriers to passage of a lipid enveloped virus.

Evaluation Studies as Topic↗

PubMed1990

Nonfulminant herpes simplex encephalitis as a cause for mesial temporal sclerosis.

Although mesial temporal sclerosis has been recognized for more than 100 years, its etiology remains unknown. It is proposed that a common infectious agent, herpes simplex virus type-1, may cause this disorder by means of a nonfulminant infection of mesial temporal lobe structures, which is resolved by the immune system and becomes gliotic in the course of healing by the central nervous system. Brain sections from a long-term experiment in a model of herpes simplex encephalitis reveal such a scar, which shows a high concentration of glial fibrillary acidic protein, without any evidence of residual herpes antigen, by immunocytochemistry.

Animals↗