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Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 91 records · Page 5Linked to original sources
PubMed1986

Amantadine resistance in clinical influenza A (H3N2) and (H1N1) virus isolates.

Thirty-nine influenza A (H1N1) and (H3N2) virus isolates were examined for their susceptibility to amantadine in allantois-on-shell (AOS) cultures. A range of susceptibilities was found when isolates were titrated in the presence of 2.5 mg/l amantadine. Further titration of resistant isolates at 25 mg/l revealed one isolate which remained totally resistant at this higher concentration. A series of cloned viruses was derived from this resistant isolate, and one other partially resistant isolate, by limiting dilution AOS passage in the absence of amantadine. When these were titrated in the presence of 25 mg/l amantadine, a heterogeneity of amantadine-resistance phenotypes was observed in both sets of virus clones. Finally, chronological ordering of clinical isolates and reference strains tested in this study suggests a higher incidence of amantadine resistance amongst more recent influenza A virus isolates.

Amantadine↗
PubMed1985

Reassortants of influenza B viruses for use in vaccines: an evaluation.

Three slightly different procedures for the preparation of influenza B virus reassortants from B/Lee/40 and B/Lyon/79, and B/Johannesburg/58 and B/Hong Kong/82 parental viruses are described. Following cloning procedures in eggs or allantois-on-shell cultures in the presence of antisera to B/Lee or B/Johannesburg, twenty-eight putative reassortants were obtained. Using SDS-PAGE to determine the migration rates of virion polypeptides, eighteen isolates from mixed infections of B/Lee with B/Lyon, and three isolates from mixed infections of B/Johannesburg with B/Hong Kong, were found to be reassortants. All reassortants possessed surface proteins derived from either B/Lyon or B/Hong Kong and one to three internal polypeptides from either B/Lee or B/Johannesburg. None of the reassortants showed a growth capacity in embryonated eggs as high as that of their B/Lee or B/Johannesburg parent viruses. The procedures used, and the influenza B reassortants thus generated, would appear to offer no major advantages over the existing methods and influenza B strains at present employed for the preparation of inactivated influenza virus vaccines.

Animals↗
PubMed1985

Antibody response and persistence in volunteers following immunization with varying dosages of a trivalent surface antigen influenza virus vaccine.

The serum antibody responses and 50% protective levels (PL50) of antibody were determined, using the SRH test, at one and twelve months post-vaccination in a group of student volunteers immunized with one of three dosages of a trivalent surface-antigen influenza virus vaccine, or with placebo. It was found that, for the H3, H1 and B haemagglutinin components present in the vaccine, a dose of 6 micrograms HA elicited high serum antibody responses at one month post-immunization. High mean antibody levels and a high incidence of volunteers with PL50 values of antibody against each of the HA components of the vaccine remained in the volunteer group twelve months later. The results are discussed in relation to the vaccine dosage used and the nature of the population immunized.

Antibodies, Viral↗
PubMed1985

Morphology and antigenicity studies on reassortant influenza (H3N2) viruses for use in inactivated vaccines.

Three influenza A (H3N2) reassortant whole virus vaccine strains with differing antibody-inducing capacities in hamsters were investigated morphologically and antigenically. Although initial measurements of virion circumference, from electron micrographs of vaccine preparations, suggested a relationship of small virion size with low immunogenicity, subsequent immunization with, and morphological investigation of, vaccine virions separated on sucrose gradients, failed to obtain populations whose antibody-inducing capacity clearly correlated with constituent virion density, size, morphology or integrity. However, antigenic investigation using single radial haemolysis (SRH) and monoclonal antibodies revealed significant differences in antigenic specificity between the strains. Furthermore, a series of H3N2 isolates, derived using standard reassortment procedures, also showed differences in antigenic specificity in their haemagglutination-inhibition (HI) reactions with monoclonal antibodies after five passages in allantois-on-shell cultures. Variation between these isolates and their A/Victoria parent virus could be detected using SRH and hamster sera raised against each isolate. These results demonstrate variation between candidate influenza A virus vaccine strains, all possessing the same surface (H3N2) glycoproteins, expressed as a consequence of the reassortant system used for their production.

Animals↗
PubMed1984

Effect of urea and uric acid on influenza virus type C. Brief report.

The replication of influenza type C/1233 virus following inoculation into the amniotic sac of embryonated hen's eggs is significantly greater than that seen in the allantoic cavity. However, optimal growth condition for amniotically propagated C/1233 occur in the allantois of 8-day old embryos incubated post-inoculation at 32 degrees C. Differences in pH levels between the amniotic and allantoic cavities did not account for the variable growth ability of C/1233 virus, but in both in vitro and in ovo studies, levels of urea and uric acid, or urea-uric acid mixtures caused significant reductions in virus yield.

Animals↗
PubMed1984

Use of zwitterionic detergent for the preparation of an influenza virus vaccine. 1: Preparation and characterization of disrupted virions.

The zwitterionic, Empigen BB an alkylbetaine based on a C12-C14 alcohol was shown to disrupt influenza A and B viruses in such a way as to retain the biological activity of the surface haemagglutinin (HA) and neuraminidase (NA) antigens. The optimal conditions required to obtain the maximum recovery of HA and NA activity from purified influenza X47 (H3N2) virus concentrate after treatment with Empigen, and the nature and the morphological appearance of the Empigen-treated preparations both before and following a sucrose density gradient purification step, are described. Matrix (M) protein was readily removed during purification, but nucleoprotein (NP) could not be separated from the surface protein activity.

Centrifugation, Density Gradient↗
PubMed1984

Use of a zwitterionic detergent for the preparation of an influenza virus vaccine: 2. Immunogenicity of Empigen-treated virus in animals.

The immunogenicity of zwitterionic detergent-disrupted influenza virus vaccine preparations, intact virus vaccine and vaccine preparations obtained by treatment of the intact virus with Triton-X 100 or cetyl trimethyl ammonium bromide (CTAB) was studied in hamsters and mice. In all experiments the intact, inactivated virus vaccine induced greater serum haemagglutination-inhibiting (HI) and neuraminidase-inhibiting (NI) antibody titres than the detergent-disrupted preparations. The serum HI antibody responses induced in hamsters and mice by Empigen-, Triton-, or CTAB-disrupted vaccines were similar, although more highly purified Empigen-disrupted preparations elicited marginally lower immune responses. In both animal species, all vaccine preparations afforded a similar degree of protection against homologous virus challenge.

Animals↗
PubMed1984

Inactivated influenza virus vaccines in man: a comparative study of subunit and split vaccines using two methods for assessment of antibody responses.

The serum antibody responses and reactions of volunteers to a trivalent subunit influenza virus vaccine prepared using cetyl trimethyl ammonium bromide (CTAB) or trivalent split vaccine prepared by ether-extraction, were essentially similar, although the antibody levels to the A/Brazil/78 (H1N1) components of the vaccine were greater in volunteers receiving the subunit preparation. Antibody responses to the vaccines were assessed using both the haemagglutination-inhibition (HI) and single radial haemolysis (SRH) tests. Although good correlation was found between the tests with respect to both antibody titres in individual sera and antibody responses in serum pairs to both A(H3N2 and H1N1) and B influenza viruses, the greater reliability of SRH, indicates this test should supplant the HI test for the routine measurement of antibody responses to influenza viruses.

Adolescent↗
PubMed1984

Interpretation of responses and protective levels of antibody against attenuated influenza A viruses using single radial haemolysis.

Antibody determinations against H3N2 and H1N1 type A influenza viruses were carried out on paired sera obtained from volunteers taking part in influenza virus vaccine studies, using both the haemagglutination-inhibition (HI) and single radial haemolysis (SRH) test. Good correlation between the HI and SRH test was found for both H3N2 and H1N1 antibody and the zone area increases corresponding to significant SRH antibody rises determined for both virus strains. In both H3N2 and H1N1 vaccine studies, intranasal infection of the volunteers with live attenuated viruses was involved and by the measurement of HI and SRH antibodies prior to and following infection, levels of antibody equating with protection against the infecting viruses could be estimated. For the HI test the antibody titres associated with 50% protection were 42 for H1N1, and 44 for H3N2 viruses; for the SRH test, 50% protection was associated with zone areas of 20.0-25.0 mm2 for both H1N1 and H3N2 viruses.

Antibodies, Viral↗
PubMed1983

Interference following dual inoculation with influenza A (H3N2) and (H1N1) viruses in ferrets and volunteers.

The effects of simultaneous inoculation with two attenuated influenza A viruses was studied in ferrets and volunteers. Groups of ferrets were inoculated with an influenza A (H3N2) or (H1N1), virus or a combination of both viruses: the temperature response, serum and local antibody response, and the change in nasal wash protein concentration was determined. The results showed that both viruses were attenuated for ferrets, and that inoculation with both viruses together did not cause clinical reactions. Serological studies on paired serum samples obtained from ferrets showed that both viruses when given separately infected all the inoculated animals; however, dual infection resulted in all ferrets being infected with the influenza A (H3N2) virus strain, but this infection interfered with infection by the influenza A (H1N1) strain. Similar investigations were carried out in volunteers. Again, the clinical reactions and temperature response of volunteers to infection by one or other of the viruses showed both strains to be attenuated for man even when given together. In addition, no adverse clinical reactions were seen in volunteers inoculated with both viruses simultaneously. Serum antibody studies showed that infection by influenza A (H1N1) virus interfered with infection by the influenza A (H2N2) virus strain. These results show evidence of interference by influenza A viruses; however, the direction of interference was one-way, and differed for ferrets and for volunteers.

Animals↗
PubMed1983

The use of the single radial haemolysis test for assessing antibody response and protective antibody levels in an influenza B vaccine study.

Single radial haemolysis (SRH) and HAI tests were used to determine the levels of antibody in sera obtained from 118 volunteers taking part in a study of influenza B/Hong Kong/73 subunit vaccine. The two tests gave similar overall results, and showed good correlation, but SRH appeared to be more sensitive for the detection of low concentrations of antibody. A greater than or equal to 45% increase in SRH zone area was found to be equivalent to a significant increase in antibody titre and on the basis of this value, the HAI and SRH tests gave similar results for responses to immunization. The concentration of antibody equivalent to a 50% protective level against a challenge virus infection was a zone area of 45 mm2 for the SRH test; this was equivalent to an HAI titre of 1:20 which has previously been established as the 50% protective level.

Antibodies, Viral↗
PubMed1983

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 1. Short-term immunity.

Groups of volunteers were immunized subcutaneously with one of three inactivated influenza virus A/USSR/77 (H1N1) vaccine preparations; a whole virus vaccine, a surface-antigen subunit adsorbed vaccine, or an aqueous surface-antigen subunit vaccine. The reactions to immunization were recorded, and the antibody response was measured 1 month later. A fourth group of volunteers were inoculated intranasally with live attentuated A/USSR/77 (H1N1) influenza virus; the reactions and antibody response of these volunteers were also measured. One month after immunization, the incidence of infection by challenge with homologous live attentuated virus was determined for all groups of volunteers. The results showed that all four vaccines used were relatively non-reactogenic, and that inactivated vaccines induced higher titres of serum antibody than the live attenuated vaccine. All the vaccines induced significant protection against challenge virus infection which was directly related to the level of serum HI antibody response.

Adolescent↗
PubMed1983

A comparison of live and inactivated influenza A (H1N1) virus vaccines. 2. Long-term immunity.

Groups of volunteers were immunized with one of three influenza virus vaccines, and the resistance to challenge infection with attenuated influenza A (H1N1) virus was measured 8 months later. The vaccines were aqueous subunit influenza A/USSR/77 (H1N1) vaccine, aqueous subunit influenza B/Hong Kong/73 vaccine, or attenuated influenza virus A (H1N1) vaccine. The B virus vaccine was included as a control to assess the incidence of natural A virus infection during the study period. A proportion of the B virus vaccinees had pre-existing A (H1N1) virus antibody and were used to study the immunity conferred by natural infection to the live virus challenge. The serum antibody responses were measured at 1 and 8 months after immunization. The results showed that all the vaccines induced serum HI antibody in a proportion of the volunteers; however, after 1 month, higher titres of serum antibody were found in volunteers given inactivated A vaccine than in those given live attenuated A virus vaccine. Eight months post-immunization the titres of serum antibody in volunteers given inactivated vaccine had declined significantly, but there were no changes in the antibody titres of those given live virus vaccine. The incidence of infection by the challenge virus at 8 months post-immunization was directly related to the serum antibody titres 1 month post-immunization; no evidence was obtained to suggest that those given live virus vaccine had a more solid immunity than those given inactivated vaccine.

Adolescent↗
PubMed1983

A graded-dose study of inactivated, surface antigen influenza B vaccine in volunteers: reactogenicity, antibody response and protection to challenge virus infection.

One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 micrograms of HA or saline alone in a 0.5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response. The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 micrograms HA and least for those given 5 micrograms HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 micrograms HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of greater than 40 following immunization: for volunteers given 5 micrograms HA the g.m.t. increased from 16.6 to 86.1; and for those given 10 and 20 micrograms HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20.

Adolescent↗
PubMed1983

Low concentrations of trifluoperazine affect striatal cells in culture.

Primary monolayer cultures of the newborn rat corpus striatum were treated with the phenothiazine trifluoperazine after various times in culture. When the drug is added to cells at least 3 weeks old, concentrations of 10(-7) and 10(-8) M appear morphologically identical to controls but show significant changes in synthesis of acetylcholine and gamma-aminobutyric acid, particularly the former. The results with these very low concentrations suggest that the drug has a highly specific effect directly on striatal cells, and that it is not acting via calmodulin.

Animals↗
PubMed1982

Transmissibility of influenza viruses in hamsters.

The growth characteristics of a series of influenza A viruses in the turbinates and lungs of hamsters was measured: in addition, the susceptibility of hamsters to infection by these viruses was also determined. These two criteria were used to give estimates of the growth potential of influenza viruses in hamsters, and the results were related to the incidence of transmission of virus from inoculated hamsters to cage-contacts. The results showed that strains of influenza virus reported as virulent for man tended to grow to higher titres in hamster nasal washings and lungs; were more infective for hamsters when inoculated by the intranasal route; and showed a high incidence of spread to cage-contacts. The methods could provide valuable measurements of virus attenuation and transmissibility for man, and the further exploitation of these techniques could facilitate the production and licensing of live, attenuated influenza virus vaccines.

Animals↗
PubMed1982

Infant rat model of attenuation for recombinant influenza viruses prepared from cold-adapted attenuated A/Ann Arbor/6/60.

The pathogenicity of 6 wild-type influenza A viruses and 21 recombinant strains prepared from wild-type viruses and cold-adapted A/Ann Arbor/6/60 virus for infant rats was determined. Thus, the titers of virus present in the turbinates and lungs of virus-infected animals was measured serially for 5 days after intranasal infection, and the ability of virus strains to promote subsequent systemic bacterial infection by Haemophilus influenzae was measured at 48 h after virus infection. The results obtained were assessed with reference to the genetic constitution of the virus strains and to virus virulence for volunteers. The results showed that virulent viruses grew to relatively high titers in rat turbinates and significantly promoted systemic infection by H. influenzae. In contrast, attenuated strains grew to lower titers and failed to promote systemic H. influenzae infection. For the strains tested, the results showed clear differences for attenuated and virulent strains, and the model was a reliable indication of virulence for humans. Although the virulent strains tended to grow to higher titers in rat lungs than did attenuated strains, exceptions were found, and this measurement could not reliably discriminate virulent and attenuated virus strains. The results suggest that infant rats can be used to assess the virulence of cold-adapted recombinant influenza virus strains, and thus, they can facilitate the development of such strains for vaccine production.

Animals↗