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Biomedical subjects

C J Peters

Publications and source records attributed to C J Peters.

At least 253 records · Page 14Linked to original sources

A Rift Valley fever vaccine trial: 2. Serological response to booster doses with a comparison of intradermal versus subcutaneous injection.

A booster dose of a formalin-inactivated, cell culture-propagated Rift Valley fever vaccine (TSI-GSD-200) was administered without significant reactogenicity to 60 volunteers 18 months after they received a three dose primary series. Blood was drawn for serological testing prior to boosting and 10, 49, and 180 days thereafter. Neutralizing antibody response was prompt, being maximum on day 10 and considerably higher than the peak titres obtained on day 42 after the initial series. A marked decline in antibody titres was evident by day 180, as seen for the primary series, but residual titres were substantially higher. The initial series was given in doses of 1.0, 0.5, 0.3, or 0.1 ml and the immune status achieved with these injections was a major determinant of the response to boostering. Secondary responses were highly dependent in magnitude and duration on the prior immune status of the recipient. Evaluation of dose and route of recall inoculation showed 1.0 ml given subcutaneously (SC) to be equivalent to 0.1 ml administered intradermally (ID), though inference should be guarded due to the small sample size. Although 0.1 ml SC dose was inferior to either, it was modestly effective. Intradermal administration of vaccine may be useful for extending the small reserve of vaccine available for use in emergency.

Adult↗

Rift Valley fever virus vaccine trial: study of neutralizing antibody response in humans.

The serological response to immunization with a formalin inactivated Rift Valley fever (RVF) vaccine was studied in 963 Swedish UN soldiers serving in the Sinai peninsula. Antibody titres were determined with a plaque reduction neutralization test (PRNT). Attempts were made to give all soldiers three injections (1 ml s.c. days 0, 7-10 and 28-30) but 128 soldiers received only two injections. In a group of 51 fully vaccinated individuals, repeated blood samples were collected. Fifty of the vaccinees seroconverted. Serum collected six weeks after the first vaccination revealed the highest antibody titres. The geometric mean titre then decreased rapidly during the following two weeks. Six months after vaccination sera were collected from 433 vaccinees who had received three injections and 379 had antibodies detectable by PRNT (88% PRNT greater than or equal to 10). The corresponding figures one and two years after vaccination were 223 seropositives out of 255 (91% PRNT greater than or equal to 10) and 91 out of 123 (74% PRNT greater than or equal to 10), respectively. Multiple stepwise regression showed that three injections gave a better antibody response than two injections. This analysis also showed that the magnitude of the antibody response was reduced with increasing age. Slight, local and general side effects were reported in 6% of the vaccinees and these reactions occurred in individuals with relatively higher antibody response.

Antibodies, Viral↗

Effect of immunosuppression on experimental Argentine hemorrhagic fever in guinea pigs.

Immunosuppression with cyclosporin A or cyclophosphamide had no apparent effect on the disease course of guinea pigs infected with a virulent strain of Junin virus. Immunosuppression of guinea pigs infected with an attenuated strain of Junin virus led to fulminating Argentine hemorrhagic fever. All immunosuppressed infected animals died. Virus distribution patterns in target organs, as determined by plaque assay and fluorescent antibody procedures, were similar to those from non-immunosuppressed animals infected with a virulent strain. Histopathological lesions in immunosuppressed guinea pigs infected with an attenuated strain of virus were similar to those in non-immunosuppressed guinea pigs infected with a virulent strain. Histological changes attributable to the immunosuppressive drug(s) were regularly observed. Immunosuppressed animals infected with attenuated Junin virus and non-immunosuppressed animals infected with virulent virus failed to develop antibody or responded at a minimal level. Virus-specific cytotoxic spleen cell activity, previously shown to be antibody dependent, failed to develop in the same animals. The presence of a competent immune response, probably serum antibody, determined whether Argentine hemorrhagic fever infection of the guinea pig was lethal or whether recovery ensued; no evidence for harmful effects of the immune response was obtained.

Animals↗

An outbreak of coxsackievirus B infection followed by one case of diabetes mellitus.

During the fall of 1979, 22/250 Swedish UN soldiers serving in Egypt were hospitalized with fever and gastroenteritis associated with aseptic meningitis. One of the 22 developed insulin dependent diabetes mellitus (IDDM) 10 weeks following the infection. The majority of the 22 patients showed significant titer rise for coxsackievirus B by plaque reduction neutralization test. The serology results indicate that coxsackievirus B4 most likely caused the outbreak. All 22 were also tested for islet cell cytoplasmic antibodies and islet cell surface antibodies and found negative. The individual developing diabetes mellitus had the HLA-DR phenotype 3,4, which is associated with IDDM.

Adult↗

Enhanced treatment of Lassa fever by immune plasma combined with ribavirin in cynomolgus monkeys.

Lassa virus-infected cynomolgus monkeys were treated with Lassa virus-immune monkey serum containing a high concentration of neutralizing antibody, the antiviral drug ribavirin, or a combination of ribavirin plus immune serum at various times after infection. When treatment was initiated early (day 0 or 4), either ribavirin (30 mg/kg of body weight per day) or immune serum alone protected monkeys. However, when the initial treatment was delayed until day 7, only four of eight ribavirin-treated and only one of six serum-treated monkeys survived. Treatment with ribavirin combined with immune serum was more successful; all infected monkeys given combination treatment survived, including six treated initially on day 10. Increased doses of ribavirin given alone were toxic. The empirical observation that combined treatment with ribavirin plus serum results in enhanced survival in experimentally infected monkeys suggests that combined treatment might benefit human patients with Lassa fever as well.

Animals↗

Two cases of hemorrhagic fever with renal syndrome in northern Greece.

Two cases of hemorrhagic fever with renal syndrome were diagnosed in woodcutters presumably exposed to wild rodents and their urine in a forest in northern Greece. The disease was characterized by acute renal insufficiency without hemorrhagic manifestations. One patient required hemodialysis, but both recovered without sequelae and developed a fourfold increase in titer of antibody to Hantaan virus, as determined by an immunofluorescence test. These are the first reported cases of hemorrhagic fever with renal syndrome in Greece.

Adult↗

Active and passive immunization against Rift Valley fever virus infection in Syrian hamsters.

The protection by active and passive immunization of Golden Syrian hamsters challenged with Rift Valley Fever (RVF) virus intraperitoneally was studied. Six groups of 10 hamsters were inoculated with different amounts of immune serum while five groups were actively immunized with different doses of a formalin-inactivated RVF vaccine. One day after passive and three weeks after active immunization all hamsters were challenged with 5000 plaque-forming units of RVF virus. Plaque reduction neutralization tests (PRNT) were performed with serum samples collected immediately before challenge. A PRNT titer of 10-20 or more was required for full protection against the RVF challenge in both actively and passively immunized hamsters. Actively immunized hamsters and control animals that succumbed to the infection died within the first 4 days after virus challenge, whereas some passively immunized hamsters died as late as 11 days post virus challenge. Animals that died early had developed massive liver necrosis, whereas late death was caused by encephalitis.

Animals↗

Passive antibody therapy of Lassa fever in cynomolgus monkeys: importance of neutralizing antibody and Lassa virus strain.

Lassa virus-infected cynomolgus monkeys were passively immunized with immune plasma of primate or human origin to gain insight into criteria for plasma selection and administration to human Lassa fever patients. Protective efficacy was correlated with neutralizing antibody concentrations, expressed as a log10 neutralization index (LNI). Convalescent Lassa-immune monkey plasma was titrated for protective efficacy in monkeys by intravenous inoculation with dilutions of plasma on the day of subcutaneous Lassa virus inoculation (day 0) and again on days 3 and 6. Monkeys that received undiluted plasma (LNI = 4.1) (1 ml/kg per treatment) survived a lethal viral dose, whereas those given a 1:3 dilution (LNI = 2.6) of this same plasma (1 ml/kg per treatment) died. Protection was restored when the volume of the 1:3 plasma dilution was increased to 3 ml/kg per treatment. Plasma diluted 1:9 or more (LNI = 1.5 or less) delayed onset and suppressed the magnitude of viremia but failed to confer protection at 3 ml/kg per treatment. Immunological enhancement, defined as increased viremia or accelerated death, did not occur following inadequate treatment. Human convalescent plasma also protected recipient monkeys; reductions in mortality and viremia were accurately predicted by the LNI of the plasma. Plasma of Liberian origin neutralized a Liberian Lassa strain more effectively than a Sierra Leone strain in vitro (LNI = 2.8 and 1.6, respectively) and protected monkeys more effectively against the Liberian strain. Geographic origin is thus a factor in the selection of optimal plasma for treatment of human Lassa fever, since geographically matched plasma is more likely to contain adequate LNI titers against homologous Lassa virus strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Detection of human immunoglobulins G and M antibodies to Rift Valley fever virus by enzyme-linked immunosorbent assay.

Rift Valley fever virus (RVFV) is an important human and animal pathogen in Africa and has been responsible for infections in travelers. Because of the aerosol infectivity and risk of dissemination of the virus, a need exists for simple, safe, serological tests for diagnosis. An enzyme-linked immunosorbent assay (ELISA) was developed to detect RVFV-specific immunoglobulins (immunoglobulin G [IgG] and IgM). In the test, a betapropiolactone-inactivated, sucrose-acetone-extracted, suckling mouse liver RVFV antigen was captured by mouse RVFV antibodies adsorbed to polystyrene plates. The test sample (human serum) was then added, and the binding of specific antibodies was indicated by alkaline phosphatase-conjugated swine anti-human IgG or IgM. A mu-capture IgM ELISA was also developed by using polystyrene plates coated with goat anti-human IgM incubated successively with serum sample, RVFV antigen, and indicator antibodies. The ELISA for RVFV-specific IgG proved to be more sensitive than hemagglutination inhibition or complement fixation tests and almost as sensitive as the plaque reduction neutralization test in detecting specific antibodies in human sera after vaccination. The two ELISA IgM tests could detect specific IgM antibodies during the first 6 weeks after RVFV vaccination. Three injections of inactivated vaccine were given on days 0, 6 to 8, and 32 to 34. ELISA IgM values for sera obtained on days 6 to 8 were negative or in the lower range of significance, on days 32 to 34 they were strongly positive, and on days 42 to 52 they were waning. Later sera were negative. The plague reduction neutralization test was negative on days 6 to 8 but rose progressively in later samples. These findings suggest that the three doses of RVFV vaccine induce a prolonged primary antibody response. The ELISA IgM could become an important tool for early diagnosis in acute human infection. A number of African sera, some of which were positive for RVFV by plaque reduction neutralization test, were also tested by ELISA IgG. There was good agreement between both tests.

Animals↗

Detection of Lassa virus antigens and Lassa virus-specific immunoglobulins G and M by enzyme-linked immunosorbent assay.

Rapid diagnosis of Lassa fever is desirable for the timely therapeutic intervention and implementation of strict quarantine procedures both in West Africa field hospitals where the disease is endemic and at international crossroads. An enzyme-linked immunosorbent assay (ELISA) to measure Lassa virus antigens in viremic sera was developed in which experimentally infected monkeys were used as a model for the human disease. In this test, Lassa virus antigens in test sera were captured in wells of microtiter plates by monkey anti-Lassa virus immunoglobulin. Guinea pig anti-Lassa virus immunoglobulin was then added, and binding of specific immunoglobulin was quantitated by the addition of rabbit anti-guinea pig immunoglobulin followed by alkaline phosphatase-labeled anti-rabbit immunoglobulin. This test detected viremia titers as low as 2.1 log10 PFU/ml in experimentally infected monkey sera, a titer often exceeded in patients with Lassa fever. Inactivation of infectious virus by beta-propiolactone or gamma-irradiation did not diminish reactivity. Antigen-ELISA concentrations increased with infectivity for the first 10 days after infection but then declined while infectivity titers remained high, suggesting that the presence of humoral antibody in viremic sera diminishes the sensitivity of the antigen ELISA. Lassa virus-specific immunoglobulin M (IgM) titers measured in an IgM capture ELISA were detectable within 10 days of infection and peaked after 36 days but remained detectable for 1.5 years. The Lassa virus-specific IgG ELISA response was slightly delayed, peaking on day 73 but declining only slightly thereafter. These studies in a realistic primate model suggest that the antigen detection ELISA or the IgM capture ELISA described, in which beta-propiolactone-inactivated sera are used, should be useful for the rapid diagnosis of human Lassa fever.

Animals↗

Detection of Rift Valley fever virus antigen by enzyme-linked immunosorbent assay.

A double-antibody (sandwich) enzyme-linked immunosorbent assay (ELISA) was adapted to detect Rift Valley fever virus antigen. Antibodies were purified from hyperimmune mouse and rabbit sera by affinity chromatography, using CNBr-activated Sepharose 4B coupled to a beta-propiolactone-inactivated sucrose-acetone-extracted suckling mouse liver antigen. In the assay, antigen was captured by mouse antibody adsorbed to polystyrene plates and then detected by reacting sequentially with rabbit anti-Rift Valley fever virus antibody and swine anti-rabbit immunoglobulin G conjugated to alkaline phosphatase. ELISA proved to be useful in measuring viral antigen in different animal systems. However, great variation was found in the amount of antigen per PFU encountered in different circumstances. The ELISA system was optimized using supernatant fluids from infected Vero cell cultures and had a sensitivity of 10(5) PFU/ml. Hamsters develop progressive viremia, much as seen in susceptible domestic animals, such as lambs; ELISA could reliably detect 10(6) PFU/ml of viremic hamster serum. Rhesus monkeys with Rift Valley fever infection were positive by ELISA even when viremias were only 5 X 10(3) PFU/ml. ELISA also proved to be useful in measuring viral antigen in infected mosquitoes.

Animals↗

Postsynaptic alpha 1-and alpha 2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat.

The contribution of postsynaptic alpha 1-and alpha 2-adrenoceptors to vascular responses was investigated in the blood perfused hindlimbs of pentobarbitone-anaesthetised dogs and chloralose-anaesthetised cats. Responses were obtained to sympathetic nerve stimulation, noradrenaline, phenylephrine and UK-14,304. In the dog and cat hindlimbs, the response to phenylephrine was reduced by the selective alpha 1-adrenoceptor antagonist, prazosin, while that to UK-14,304, in the dog, was reduced by the alpha 2-adrenoceptor antagonist, rauwolscine. Responses to noradrenaline and sympathetic nerve stimulation were only partially blocked by prazosin in both the dog and cat, but were further reduced by the addition of rauwolscine. These results suggest that the hindlimb vasculature of the dog and cat responds to neuronally released, as well as exogenous, noradrenaline by activation of both postsynaptic alpha 1- and alpha 2-adrenoceptors.

Animals↗