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P F Wright

Publications and source records attributed to P F Wright.

At least 19 recordsLinked to original sources
PubMed1992

Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network.

Serum antibody responses were studied in detail in four vaccinia-naive volunteers in a phase I trial evaluating primary vaccination with a recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein (HIVAC-1e, Oncogen/Bristol-Myers Squibb), followed by booster immunization with baculovirus-derived rgp160 (VaxSyn, MicroGeneSys). Prior to boosting, low-titer Fc receptor (FcR)-mediated, antibody-dependent enhancing (ADE) activity was detected in two of four volunteers but no IgM, IgG, IgA, neutralizing activity, or complement-mediated ADE activity was detected. Two weeks after boosting, all four volunteers developed HIV-1-specific IgG with titers of 1:160 to 1:640 by immunofluorescence assay. IgG1 was present in sera from each individual, while IgG2 and IgG3 were present in sera from two individuals, and IgG4 was present in serum from one individual. IgM and IgA were undetectable in all sera. Only one volunteer had IgG to the heterologous HIV-1 isolates, RF, MN, and SF2, after boosting. Serum from this volunteer neutralized the vaccine strain, LAV/IIIB, but not the heterologous strains, RF, MN, and SF2. Antibodies from the remaining volunteers had no neutralizing activity. The neutralizing serum had a positive reaction in a peptide-based ELISA utilizing a peptide corresponding to the principal neutralizing domain of the third hypervariable region (i.e., V3 loop) of the envelope glycoprotein. Neutralizing activity was partially removed by adsorption to this peptide, suggesting that it contained a type-specific neutralizing vaccine epitope. A low titer (1:40 to 1:80) of complement-mediated ADE activity to HIV-1 IIIB was present in sera from three vaccinees after boosting. FcR-ADE activity for HIV-1 SF2 and SF-128A were present in sera from two of these three vaccinees. None of the volunteers developed antisyncytial antibodies. These results indicate that inoculation with recombinant vaccinia followed by rgp160 boosting is the most effective strategy to date for inducing serum antibodies to the envelope glycoproteins of HIV-1, but further study is needed to optimize the functionality and cross-reactivity of these responses.

AIDS Vaccines↗
PubMed1992

Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network.

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.

AIDS Vaccines↗
PubMed1992

Simultaneous screening of bovine sera for antibodies to bluetongue and epizootic hemorrhagic disease of deer viruses by enzyme-linked immunosorbent assay.

An indirect enzyme-linked immunosorbent assay (I-ELISA) is described for simultaneous screening of bovine sera for detection of antibodies to bluetongue (BT) and epizootic hemorrhagic disease of deer (EHD) viruses (V). Optimal dilutions of BTV and EHDV antigens were combined and allowed to absorb on to the wells of microtiter plates. Appropriately diluted (1:100) bovine sera were allowed to incubate and the bound antibodies were detected by a murine monoclonal antibody (MAb) to bovine immunoglobulin (H-Chain) conjugated with horseradish peroxidase. The performance of the combined (C) I-ELISA in detecting antibodies to BTV and EHDV in sequential serum samples from calves experimentally inoculated with BTV, serotype 10, EHDV, serotype 1 (New Jersey) or EHDV serotype 2 (Alberta) was evaluated. Comparable antibody profiles were demonstrable by the CI-ELISA and separate I-ELISAs using either BTV or EHDV antigens. The results suggest that the CI-ELISA offers many advantages over the standard agar gel immunodiffusion (AGID) test and has potential application as a rapid, sensitive, inter-group-specific and inexpensive test for simultaneous screening of bovine sera for antibodies to BTV and/or EHDV.

Animals↗
PubMed1992

Optimization and standardization of an enzyme-linked immunosorbent assay protocol for serodiagnosis of Actinobacillus pleuropneumoniae serotype 5.

An indirect enzyme-linked immunosorbent assay protocol has been optimized with special emphasis given to assay standardization and quality control. Technical aspects such as choice of a microplate, antigen immobilization, buffer composition, optimal screening dilution of sera, and kinetics of the enzymatic reaction were studied and evaluated in order to design a standard protocol offering maximal analytical sensitivity and specificity, as well as to obtain minimal within- and between-plate variability. Among the 27 plates tested, the Nunc 475-094 and 269-620 immunoplates were found to be the best in terms of high positive-to-negative ratio and low variability. No significant differences in antigen immobilization were found by using buffers of various compositions or pHs; however, the presence of magnesium ions (Mg2+; 0.02 M) resulted in a twofold increase in nonspecific background. An optimal screening dilution of sera was established at 1:200. A 1-h incubation period for test serum was found to be optimal. Maximum enzymatic activity for peroxidase was obtained by adjusting both substrate (H2O2) and hydrogen donor [2,2' -azinobis(3-ethylbenz-thiazoline sulfonic acid)] concentrations to 4 and 1 mM, respectively. To control between-plate variability, a timing protocol was adopted. Within-plate variability was also controlled by using a sample placement configuration pattern. Sliding scales were determined by repeated testing of a cross section of samples to set acceptance limits for both within- and between-plate variability. These limits were used in a quality control program to monitor assay performance. The results obtained suggest that this standardized protocol might be useful in the serodiagnosis of Actinobacillus pleuropneumoniae serotype 5.

Actinobacillus Infections↗
PubMed1992

Concentrations of individual serum or plasma bile acids in workers exposed to chlorinated aliphatic hydrocarbons.

Individual serum or plasma bile acid concentrations were measured by high performance liquid chromatography in two groups of workers with differing exposures: to hexachlorobutadiene (HCBD) and a mixture of other chlorinated solvents (SOLVENT) in study A; and trichloroethylene (TCE) in study B. Exposures to HCBD and TCE were associated with highly significant increases in a number of individual and summed bile acid measures, with a dose effect relation shown for HCBD. Exposure to SOLVENT was associated with significant decreases in three bile acid measures but this may have been due to misclassification of exposure. No association was found between any of the exposures and any of the standard tests of liver function. This preliminary study suggests that some chlorinated hydrocarbons are associated with raised bile acid concentrations in the blood of exposed workers. It may be that the changes in such concentrations reflect early and small disturbances of liver function. The significance and mechanism of the changes are yet to be determined.

Adult↗
PubMed1992

Competitive ELISA for serodiagnosis of bluetongue: evaluation of group-specific monoclonal antibodies and expressed VP7 antigen.

The performance of 2 competitive enzyme-linked immunosorbent assays (C-ELISA) was compared with the reference C-ELISA I for the detection of antibodies to bluetongue virus (BTV). One of the assays (C-ELISA II) used a group-specific monoclonal antibody (MAb) to BTV, obtained from the American Type Culture Collection (8A3B-6) and tissue culture (TC)-derived BTV antigen (Ag), and the other assay (C-ELISA III) used BTV core protein VP7 (expressed in yeast) and the reference MAb (Pirbright Laboratory, 3-17-A3). Test sera were obtained by sequential blood samples from 22 calves, each inoculated with a different serotype (T) of BTV (South African [SA] T-1-T-16 and T-18-T-20 and USA T-11, T-13, and T-17). Sera were also obtained from 4 calves and 4 sheep inoculated with USA BTV T-10 and from several groups of calves exposed to single or multiple doses of epizootic hemorrhagic disease virus (EHDV) T-1-T-4 grown in TC (BHK-21) or suckling mouse brain (SMB). A total of 618 bovine and ovine field sera collected from BT-free and BT-endemic areas were also tested. The C-ELISA III was more sensitive than the C-ELISA II in the detection of anti-BTV antibody in sera from cattle and sheep early after infection with BTV. Seroconversion was demonstrated by the 3 C-ELISAs in all animals inoculated with BTV by 20 days postinfection (DPI), except in calves that received SA T-3 or USA T-13, which became positive at 40 DPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Development and evaluation of an enzyme-linked immunosorbent assay for detection of bovine antibodies to epizootic hemorrhagic disease of deer viruses.

An indirect enzyme-linked immunosorbent assay (I.ELISA) is described for detection of bovine serum antibody to epizootic hemorrhagic diseases of deer virus (EHDV). Serum samples, at a dilution of 1:200, were incubated with group-specific EHDV antigens, pre-adsorbed to microtiter plates. Bound antibodies were detected by a murine monoclonal antibody to bovine immunoglobulin (Ig)G1 (heavy-chain specific) conjugated with horseradish peroxidase. The performance of the I.ELISA in detecting antibodies to EHDV in sequential serum samples from calves experimentally infected with serotypes 1,2,3 and 4 was evaluated. The I.ELISA detected EHDV antibodies from 14 days postinfection when seroconversion by the standard agar gel immunodiffusion (AGID) test was also evident. The group-specific antibodies to EHDV increased exponentially during the first two to four weeks postinfection and remained relatively stable for about 12 months in some calves. Unlike observations with the AGID test, no reaction was seen in the I.ELISA between blue-tongue virus (BTV) antigen and sera from calves given a single dose of EHDV. The performance of the I.ELISA and AGID were compared using 3,135 AGID negative bovine field sera from herds in Ontario, Alberta and British Columbia and 130 AGID positive samples collected from cattle in 1987 and 1988 during and after outbreaks of EHD in the Okanagan Valley, British Columbia. The specificity and sensitivity of the assay relative to the AGID test were 99.3% and 91.5% respectively, with an overall agreement of 99.0% between the tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Perinatal transmission of human immunodeficiency virus-1 infection and maternal immunization strategies for prevention.

OBJECTIVES: To review the current understanding of the epidemiologic and pathogenetic features of human immunodeficiency virus-1 (HIV-1) infection in pregnancy and perinatal HIV infection, and to explore immunization strategies for preventing maternal-infant transmission of HIV. DATA SOURCES: MEDLINE data base and reference lists of articles were used to identify relevant papers. Reports from conferences were noted if the data had not yet been published. METHODS OF STUDY SELECTION: We reviewed all English-language papers pertaining to maternal or fetal infection with HIV, immunology of HIV infection, immunization of pregnant women, or immunization against HIV. DATA EXTRACTION AND SYNTHESIS: Human immunodeficiency virus infection of women is increasing, and vertical transmission of HIV to children is a growing problem. There is evidence for intrauterine, intrapartum, and immediate postpartum transmission, but it is thought that the majority of transmissions occur peripartum by a minor subset of the maternal HIV-1 strains. Diagnostic advances include measurement of HIV-specific immunoglobulin A (IgA) and improved systems for polymerase chain reaction and virus isolation from potentially infected infants. Clinical and immunologic correlates of transmission remain uncertain. CONCLUSIONS: The epidemiology of transmission must be determined in more diverse populations. The timing and pathogenesis of HIV transmission from infected mother to fetus require better description, and improved diagnostic tools are needed. Immunologic and mechanical determinants that prevent transmission in the majority of cases need to be identified more precisely. Clinical trials to evaluate active immunization of HIV-infected pregnant women with candidate AIDS vaccines will potentially help answer many of these questions.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Reinfection of mice with respiratory syncytial virus.

A BALB/c model of respiratory syncytial virus infection has been developed in which high-titered replication occurs in lung, immunological infiltrates in lung can be detected histologically, and illness can be consistently reproduced. The immunodeterminants of RSV reinfection in this system were investigated by rechallenging mice with RSV early (less than 2 months after primary infection) and late (16 to 21 months after primary infection) and correlating illness and titer of RSV isolated from lungs and noses with RSV-specific serological responses and lung histology. After early rechallenge, RSV was cleared within 24 hours from both nose and lung. After late rechallenge, RSV was isolated at 72 hours from nose in 21/24 mice, but from lung in only 5/24 mice. Isolation of RSV from lung after rechallenge was associated with low RSV-specific antibody titers measured by ELISA and plaque-reduction neutralization. The presence of lymphocyte aggregates around the bronchovascular bundles was associated with inability to isolate RSV from lung and lack of illness. The basophilic lymphocytes were small and uniform in size with dense nuclei and a small amount of cytoplasm. These studies demonstrate that nasal and pulmonary reinfection with RSV is possible in mice after late rechallenge. The studies also indicate the potential importance of RSV-specific antibody in protecting lung from reinfection.

Animals↗
PubMed1991

Effects of trichloroethylene on hepatic and splenic lymphocytotoxic activities in rodents.

The effects of trichloroethylene (TRI), a widely used industrial solvent, on various immunological and toxicological parameters have been examined in Sprague-Dawley rats and B6C3F1 mice. Rats were administered TRI in vivo at 0.05, 0.5 and 5.0 mmol/kg per day intraperitoneally (i.p.) for 3 days. Mice were similarly treated with TRI at 10.0 mmol/kg. The highest TRI dose resulted in decreased splenocyte count and relative spleen weights, in rats and mice respectively and inhibition of hepatic natural killer cell (NK), natural cytotoxic cell (NC) and NPK cell (a newly described immune cell killing) activities in both rats and mice. High dose TRI in vitro resulted in minor decreases (less than 10%) in splenocyte viability, inhibition of LPS-stimulated mitogenesis in rat cells and marked inhibitions of NK and NC activities in all groups of effector cells. At the lowest in vitro dose mouse hepatic NK activity was still inhibited. Overall the data show that TRI is able to inhibit the activity of lymphocytotoxic cells which are involved in the immune surveillance of cancerous cells. This inhibition is particularly evident in the liver after in vivo administration and both liver and spleen cells after in vitro exposure. This suggests the possibility that compromised immune function may play a role in the carcinogenic responses in experimental animals on exposure to TRI.

Animals↗
PubMed1991

A species/strain comparison of hepatic natural lymphocytotoxic activities in rats and mice.

The natural killer (NK) and natural cytotoxic (NC) cell activities in livers from certain rat and mouse strains were compared. This included the two rodent strains used in animal carcinogenicity bioassays, i.e. Fischer 344 and B6C3F1 mice. Sprague-Dawley and Fischer 344 rats exhibited high hepatic NK activity, which was greater than the levels seen in all of the five mouse strains studied. However, the hepatic NC activity in rats was comparable to the activities observed in C57BL and BALB/c mice. An inverse relationship was observed between the two tumoricidal activities in all but one of the mouse strains examined; that is (at 8 weeks of age), NK activity: C3H greater than B6C3F1 greater than CBA greater than BALB/c; NC activity: BALB/c much greater than CBA greater than B6C3F1 greater than C3H. The C57BL mouse strain was the only strain to express both activities at comparatively high levels. Female mice exhibited a similar profile of cytotoxic activities. Rats also possessed high activities of a presently ill-defined tumoricidal activity, this being the spontaneous P815 mastocytoma killing by unstimulated effector cells, over an 18 h period. Both adherent and nonadherent effector cells from rat livers, but only the nonadherent cell population isolated from male mouse livers, exhibited this activity which may represent a distinct hepato-specific population of natural lymphocytotoxic effector cells. The tumoricidal activities in liver-derived cells were greater than those of effector cells isolated from the spleen. The differences in natural immunity reported in this study may be related to the varying background incidences of hepatic tumors, i.e. the mouse strains susceptible to high background incidences of liver tumors have relatively low natural immunity, whereas the two mouse strains resistant to hepatic tumors possess high levels of at least one hepatic NLC activity. Similarly, rats have relatively low hepatic tumor rates and high levels of hepatic natural immunity.

Age Factors↗
PubMed1991

Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children.

A cold-adapted (ca) influenza B reassortant vaccine consisting of two genes encoding the hemagglutinin and neuraminidase from wild-type influenza B/Ann Arbor/1/86 virus and the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus was evaluated in 18 seropositive and 57 seronegative infants and children. The ca reassortant was infectious in seronegative vaccinees, with an estimated 50% human infectious dose of 10(2.5) TCID50. Nasal wash specimens from vaccinees retained the temperature-sensitive phenotype, indicating that the virus was phenotypically stable after replication in fully susceptible children. The vaccine was highly immunogenic in the seronegative vaccinees; 54% of the seropositive vaccinees also developed an increase in serum antibody. The ca vaccine was well tolerated, with only a mild increase in upper respiratory tract symptoms seen in the seronegative vaccinees. These studies indicate that the B/Ann Arbor/1/86 ca reassortant is safe, immunogenic, and phenotypically stable in infants and children.

Antibodies, Viral↗
PubMed1991

Simultaneous administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children.

Two rotavirus vaccine strains representing VP7 serotypes 1 and 2 derived by reassortment between a rhesus rotavirus master strain, MMU18006, and either of two human rotavirus strains were administered simultaneously to infants and young children to assess potential interactions between strains. Children were observed in a day care setting for 10 days after vaccine administration for clinical symptoms, evidence of vaccine transmission, and patterns of viral shedding. Serum and local antibody responses were measured. The ratio of input virus strongly influenced the amount of each strain recovered from the child. Regardless of dose of virus administered, the neutralizing antibody response to the VP7 glycoprotein, the serotype determinant, was diminished in a bivalent preparation compared with a monovalent vaccine. Additional strategies must be sought to induce immunity against the multiple serotypes of human rotavirus before broad immunity will be established.

Administration, Oral↗
PubMed1991

Respiratory syncytial virus infection in anti-mu-treated mice.

BALB/c mice were depleted of B cells by anti-mu treatment to investigate the pathogenesis of respiratory syncytial virus (RSV) infection in the absence of antibody. Termination of RSV replication after primary infection occurred with the same kinetics in anti-mu-treated mice as in phosphate-buffered saline (PBS)-treated controls. Yet, when rechallenged, anti-mu-treated mice were more permissive to RSV replication than PBS-treated controls. Anti-mu-treated mice also experienced greater illness than PBS-treated controls during both primary infection and rechallenge. Passive transfer of RSV-specific immune serum to anti-mu-treated mice before rechallenge reconstituted complete protection from RSV replication and diminished illness. Thus, RSV-specific antibody is not required to terminate RSV replication in primary infection, but without antibody, only partial immunity against rechallenge is induced. While it is unknown whether the mechanism is a direct effect on RSV titer or modulation of the illness-causing cellular immune response, the presence of RSV-specific antibody reduces illness in both primary RSV infection and rechallenge of mice.

Animals↗
PubMed1991

Imaging of pediatric mediastinal histoplasmosis.

Histoplasmosis can present a diagnostic dilemma if unusually large masses of lymph nodes, invasive mediastinal fibrosis, or pericarditis result from the infection. These rare, late sequelae are often first suspected from findings on chest radiographs obtained for unrelated reasons. Organisms are not always evident at histologic analysis at this stage. Mediastinal granulomas consist of lobulated masses of enlarged lymph nodes with central caseation, a peripheral thin capsule, and, occasionally, calcification. The mass does not invade or compromise adjacent anatomic structures. Mediastinal fibrosis invades and can seriously compromise the function of the tracheobronchial tree, superior vena cava, pulmonary arteries and veins, and esophagus; its symptoms mimic those of many other disorders. Pericarditis is commonly accompanied by pericardial effusion, pneumonia, and adenopathy. Although the radiologic findings of these conditions are nonspecific, they can be used with the clinical findings to suggest a diagnosis. Complications of histoplasmosis should be included in the differential diagnosis for patients residing in areas endemic to Histoplasma capsulatum.

Adolescent↗