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G Biberfeld

Publications and source records attributed to G Biberfeld.

At least 91 records · Page 5Linked to original sources
PubMed1995

B-cell lymphomagenesis in SIV-immunosuppressed cynomolgus monkeys.

B-cell lymphomas developed frequently (approx. 40%) in SIVsm (SMM3) immunosuppressed monkeys and were mostly extranodal, aggressive and all associated with an EBV-related simian herpes virus operationally designated herpes virus Macaca fascicularis (HVMF-I). Lymphoma tissues from 21 monkeys were studied by PCR and DNA PAGE for mono/oligoclonality of the VDJ-rearranged IgH genes. Most lymphomas (n = 15) showed a monoclonal and approximately 1/3 (n = 6) an oligoclonal VDJ rearrangement pattern. The time after infection to tumor presentation was significantly shorter for oligoclonal than for monoclonal lymphomas, suggesting that oligoclonal selection frequently precedes the outgrowth of a single malignant clone. Comparison of the VDJ rearrangements in an established lymphoma cell line and the original, oligoclonal lymphoma tissue indicated in vitro selection of one HVMF-infected clone. Longitudinal studies of sequential lymph-node biopsies showed that the malignant lymphoma clone in 3 out of 8 lymphomas could be identified as a predominant clone in lymph nodes 2-12 months after SIV infection and 6-10 months before clinical presentation of the lymphomas. VDJ-rearranged DNA corresponding to that of the lymphomas was also detected in most sera at the time of lymphoma manifestation but not in corresponding PBL preparations. Clearly, the SIVsm AIDS model in cynomolgus monkeys represents a powerful tool for biological and clinical studies of herpes-virus-associated lymphomagenesis in immunosuppressed states.

Animals↗
PubMed1995

Thymic immunopathology and progression of SIVsm infection in cynomolgus monkeys.

Thymuses from 22 cynomolgus monkeys infected with simian immunodeficiency virus (SIVsm) developed characteristic cortical and medullary changes including formation of B-cell follicles (8/21) and accumulation of virus immune complexes. Advanced thymic histopathology was correlated with more pronounced immunodeficiency. SIVsm provirus was detected by polymerase chain reaction (PCR) in most (16/18) thymuses and spliced viral env mRNA in 3 (3/7) thymuses with advanced histopathologic changes indicative of thymic SIVsm replication. By combined in situ hybridization (ISH) and immunohistochemistry, viral RNA was localized mainly to the follicular dendritic network, macrophages, multinucleated giant cells, and lymphocytes of the medullary regions. Latent infection by an Epstein-Barr-related herpesvirus (HVMF1) was also found by PCR and by ISH in medullary regions of three (3 of 8) thymuses with B-cell follicles, suggestive of an inductive role for B-cell proliferation in these thymuses. In a control group of HIV-2-infected nonimmunosuppressed monkeys, no comparable thymic changes were observed. Our results indicate that SIV, and probably by analogy HIV, can have direct and diverse pathogenic effects on the thymus that are important in the development of simian (human) AIDS.

Animals↗
PubMed1995

Large-scale evaluation of an alternative strategy for confirmation of HIV antibodies.

OBJECTIVE: To retrospectively compare the accuracy of combinations of two enzyme-linked immunosorbent assays (ELISAs) with a Western blot based strategy for identification of human immunodeficiency virus type 1 (HIV-1) seropositivity. MATERIALS AND METHODS: 48,977 sera, sent to the National Bacteriological Laboratory, Stockholm, Sweden, for HIV antibody determinations between October 1988 and June 1993, were investigated. All samples were tested in parallel with two different ELISAs, either Abbott Recombinant HIV-1 EIA and Wellcozyme Recombinant Anti-HIV-1 EIA, or Enzygnost Anti-HIV-1/2 and Wellcozyme Recombinant Anti-HIV-1 EIA, or Enzygnost Anti-HIV-1/2 and Wellcozyme Anti-HIV-1+2 EIA. 1565 sera repeatedly reactive by one or both ELISAs were investigated by Western blot (WB). Furthermore, a total of 2820 referred sera, screen reactive at primary laboratories but negative on our combinations of two ELISAs were analysed by WB. RESULTS: Out of 1244 truly HIV antibody positive samples 1203 were WB positive and 41 (3.4%) were WB indeterminate. A sensitivity of 100% was obtained by all three combinations of two ELISAs on examination of these 1244 sera including repeated testing of 5 samples with initially discrepant results. Among 2820 sera from HIV-negative individuals 649 (23%) sera were WB indeterminate. The combination of Enzygnost (indirect test with synthetic peptides) and Wellcozyme (sandwich test with recombinant and synthetic peptides) Anti-HIV 1+2 EIAs was 100% specific when used for analysis of 9111 sera. One of 30,323 HIV-1 antibody negative sera tested was initially reactive on both Enzygnost Anti-HIV 1+2 and Wellcozyme Recombinant Anti-HIV-1 EIA (competitive assay) but was found to be negative by repeated testing, resulting in a specificity of 100% for that combination of ELISAs. Abbott Recombinant Anti-HIV-1 EIA (indirect assay) combined with Wellcozyme Recombinant Anti-HIV-1 EIA was initially falsely reactive with 12 of 8272 sera of which 6 were repeatedly reactive. CONCLUSIONS: This large-scale evaluation demonstrates that combinations of two ELISAs based on different test principles and antigens increase the accuracy of the HIV antibody determination and could be used as an alternative or complement to WB.

Journal Article↗
PubMed1995

Evaluation of HIV-1/HIV-2 immunoblots for detection of HIV-2 antibodies.

OBJECTIVE: To evaluate the sensitivity of commercially available HIV-2 immunoblots and to identify the HIV-2 glycoproteins on Western blots. METHODS: HIV-2 Western blot (WB) strips commercially available from Diagnostic Biotechnology, Diagnostic Pasteur and Cambridge Biotech and in-house HIV-2 WB strips were investigated by monoclonal HIV-2 gp36 and gp125 antibodies for identification of the glycoproteins. The WB strips and commercially available HIV-1/HIV-2 line immunoassays (LIAs) from Diagnostic Pasteur (PEPTI-LAV 1-2), Diagnostic Biotechnology (version 2.2) and Innogenetics (INNO-LIA HIV-1/HIV-2 ab) were analyzed by seroconversion panels from HIV-2 infected cynomolgus monkeys (Macaca fascicularis) to investigate their sensitivity for detection of HIV-2 antibodies. The LIAs were also investigated by use of 100 HIV-2 antibody positive human sera from Guinea Bissau. The in-house WB strips contained HIV-2/SBL-6669 antigen treated with various concentrations of sodium dodecyl sulphate (SDS, 0-2%) at 37 degrees C or 100 degrees C for various times to obtain gp36 in oligomeric and/or monomeric form. RESULTS: By use of monoclonal antibodies, WB strips from Diagnostic Biotechnology and Diagnostic Pasteur were shown to contain gp125 as well as monomeric and oligomeric forms of gp36, whereas Cambridge WB strips contained mainly oligomeric gp36 and no detectable gp125. The sensitivity of the WB strips for detection of HIV-2 seroconversion was similar if WB seropositivity was defined as reactivity with p24 and one envelope protein. When the WHO WB criteria were applied requiring reactivity with at least two envelope proteins for positivity, the sensitivity of the WB strips from Diagnostic Biotechnology and Diagnostic Pasteur was retained, whereas the sensitivity of Cambridge Biotech WB strips was reduced. Among 100 HIV-2 antibody positive human sera all were reactive on PEPTI-LAV 1-2 and INNO-LIA HIV-1/HIV-2 ab, but two of the hundred sera failed to react with the HIV-2 synthetic peptide band on Diagnostic Biotechnology version 2.2 WB strips. On in-house WB strips the relation between monomeric and oligomeric gp36 was changed by altering the SDS concentration and the temperature. Thus the monomeric form increased with the SDS concentration and the temperature. The sensitivity for detection of antibodies during seroconversion did not differ between the monomeric and oligomeric forms of gp36. CONCLUSIONS: The sensitivity for detection of HIV-2 antibodies during seroconversion was independent of the oligomeric or monomeric structure of the transmembrane glycoprotein. One of the three commercial WB kits tested had a lower sensitivity for detection of HIV-2 seroconversion compared with the other two kits when the WHO criteria for WB positivity were used.

Journal Article↗
PubMed1995

Early diagnosis of HIV-1 infection in infants in Dar es Salaam, Tanzania.

OBJECTIVES: To evaluate two simple methods, an immune complex dissociation (ICD) p24 antigen assay and an HIV-1-specific IgA antibody assay, for the early demonstration of HIV-1 infection in infants, using the polymerase chain reaction (PCR) as the reference method. DESIGN AND SETTING: Group A: 143 HIV-1-seropositive and 134 -seronegative mothers and their infants were recruited at delivery at the main hospital in Dar es Salaam, Tanzania. Group B: 26 HIV-PCR-positive hospitalized children in Dar es Salaam, 3-15 months old and suspected of having an HIV-related illness. METHODS: Blood samples were taken from mothers and infants in group A at intervals during the children's first 24 months and once from each of the children in group B. Peripheral blood mononuclear cells were tested by nested PCR for viral DNA. Plasma samples were tested by the Coulter p24 antigen (ag) enzyme-linked immunosorbent assay (ELISA) after acid dissociation of p24 antigen-antibody complexes. All p24-ag-positive reactions were confirmed by neutralization. Viral specific IgA antibodies were demonstrated in plasma by a modified ELISA. RESULTS: One hundred and sixty-three of 174 samples from seropositive mothers were PCR-positive (sensitivity 93.7%) and 612 of 614 samples from seronegative mothers and children of seronegative mothers were PCR-negative (specificity 99.7%). Twenty-nine of 145 (20.0%) children born to seropositive mothers were positive by PCR when tested during the first year of life. By use of both the p24 ag ELISA and the IgA antibody ELISA in combination, HIV-1 infection was detected in 9 of 17 (53%) PCR-positive children 1-8 weeks old, in 15 of 18 (83%) PCR-positive children 9-26 weeks old and in 23 of 24 (96%) PCR-positive children 27-52 weeks old. The specificities of the p24 ag ELISA and the IgA ELISA were 100%. CONCLUSIONS: The p24 ag assay and the IgA antibody ELISA, when used in combination, had a high sensitivity and specificity for detection of HIV-1 infection in infants, especially in those above the age of 6 months.

Journal Article↗
PubMed1995

Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine.

The aim of this study was to test the ability of a live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine to protect cynomolgus monkeys against superinfection with a pathogenic simian immunodeficiency virus (SIVsm). This report is an update on our previously reported observation period of nine months. The new data here show that three of four monkeys vaccinated with live HIV-2 were protected against immunosuppression and SIV-induced disease during more than five years of follow-up. The quality of the immunity was permissive for infection, but monkeys that survived showed restricted viral replication in peripheral blood and lymph nodes. This study shows that it is possible to induce protection against a pathogenic heterologous primate lentivirus and to prevent disease in vaccinated monkeys even if infection is not prevented. These findings provide evidence that protection against AIDS can be achieved by immunization.

AIDS Vaccines↗
PubMed1995

HTLV infections among Swedish intravenous drug users in 1992.

Serum samples collected in 1992 from 1158 intravenous drug users (IVDUs) in Stockholm, Sweden, were tested retrospectively for antibodies to human T-lymphotropic virus type I and II (HTLV-I and II). The overall prevalence rate of HTLV infections was 2.4% (28/1158). A majority of the HTLV infections were caused by HTLV-II (27/28). A significant association between HTLV-II and HIV-1 seropositivity was found, the prevalence of HTLV-II infection being 11.4% (11/96) in HIV-seropositive individuals compared with 1.5% (16/1062) in HIV-seronegative persons (p < 0.001). All the HTLV-infected individuals were of Scandinavian origin. No significant differences in age and sex distribution were observed in HTLV-infected persons compared to seronegative individuals. This study confirms that HTLV-II infection is present in the Swedish IVDU population and the findings provide baseline information for future epidemiological studies.

Adolescent↗
PubMed1994

Stable biological and antigenic characteristics of HIV-2SBL6669 in nonpathogenic infection of macaques.

The purpose of the present study was to investigate if the biological and antigenic properties of human immunodeficiency virus type 2 change over time in cynomolgus macaques (Macaca fascicularis) experimentally infected with HIV-2SBL6669. Sequential virus isolates and serum samples were obtained during a 2-year period and studied in autologous neutralization assays. All six macaques studied seroconverted shortly after infection and remained healthy during the observation period. Virus could be isolated from all six animals during the first 100 days postinfection. Thereafter four monkeys became virus isolation negative, either permanently or transiently (two macaques each), whereas two macaques remained virus isolation positive during the entire observation period. Sequential reisolates from the macaques invariably replicated in HUT-78, U937-2, and Jurkat-tat cell lines, similarly to the HIV-2SBL6669 inoculum virus. The ability to produce neutralizing antibodies correlated with positive virus isolations, hence four macaques produced neutralizing antibodies against inoculum virus and sequential reisolates. Once the neutralizing antibody appeared, sequential reisolates obtained at both early and late time after infection were neutralized, indicating that the neutralizing epitopes of the virus are conserved in the infected animals over time. This is different from the pathogenic SIVsm infection in macaques or HIV-1 infection in humans, where emergence of neutralization resistant variants seems to be the rule. In contrast, in HIV-2-infected macaques the biological properties of the virus are stable and the neutralizing antibody response shows extensive cross-reactivity.

Animals↗
PubMed1994

Evaluation of the WHO human immunodeficiency virus (HIV) antibody testing strategy for the diagnosis of HIV infection.

OBJECTIVE: To evaluate a WHO testing strategy based on the use of two consecutive enzyme-linked immunosorbent assays (ELISA) as an alternative to ELISA followed by Western blotting (WB) for the serologic diagnosis of HIV infection. STUDY DESIGN: The study was of 2069 consecutive serum specimens from patients suspected of HIV infection received for HIV diagnostic testing at the HIV laboratory, Muhimbili Medical Centre, Dar es Salaam. The strategy involved testing all sera with Behring indirect anti-HIV 1 + 2 peptide ELISA, followed by Wellcozyme anti-HIV-1 recombinant competitive ELISA on those sera reactive by the first ELISA. WB was done on a sample of the sera reactive on both ELISAs and on all those giving discordant results on the two ELISAs. Of the 2069 sera tested, 837 (40.5%) were negative on the first ELISA, 1172 (56.6%) were reactive on both ELISAs and 60 (2.9%) were initially reactive on the first test but not on the second assay. RESULTS: Of the 1172 sera reactive on both ELISAs, 329 (28.1%) were tested by WB. The diagnostic accuracy of the WHO alternative testing strategy using WB confirmation as the 'gold' standard was as follows: sensitivity 99.4% (326/328), specificity 99.7%, (893/896), positive predictive value 99.1% (328/331) and negative predictive value 99.8% (893/895). Repeated testing by ELISA of the sera which initially gave discordant results on the two ELISAs increased the sensitivity to 100%. Three sera giving false positive reactions on both ELISAs became negative on both ELISAs after retesting. In order to achieve a specificity and a positive predictive value of 100%, it would have been necessary to subject all sera reacting on both ELISAs to retesting on one ELISA. CONCLUSIONS: A second ELISA based on different antigens and a different test principle compared with the first ELISA could be used as an alternative to the WB assay for confirmation of HIV antibodies. However, some modifications of the WHO strategy for diagnostic HIV antibody testing were required in order to maximize the diagnostic accuracy.

Journal Article↗
PubMed1994

Long-standing protection of macaques against cell-free HIV-2 with a HIV-2 iscom vaccine.

We investigated the capacity of two immunostimulating-complex (iscom) formulations including inactivated native HIV-2 viral proteins and selected peptides to induce protective immunity against HIV-2 in a nonhuman primate. Four cynomolgus monkeys were first immunized with five i.m. injections of purified detergent-disrupted HIV-2 virions (total dose, 0.7 mg) in iscoms over a period of 16 months. At months 18 and 20, all four macaques were given booster immunizations with iscom-coupled V3-derived synthetic peptides representing a dominating neutralizing region of HIV-2 gp125. Two weeks after the final dose of vaccine, the four vaccinated animals, together with four controls, were challenged i.v. with 10 monkey infectious doses (MID50) of monkey-cell-grown homologous cell-free virus, HIV-2SBL-6669/H5. After the challenge, the four control animals became readily infected; however, three of four vaccinated animals were protected as shown by repeated negative virus isolations and negative polymerase chain reaction for viral DNA and by failure to transmit HIV-2 infection with whole blood and lymph node cells into naive cynomolgus macaques. One of three protected animals showed an anamnestic antibody response to a dominating antigenic site, indicating possible limited virus replication. The vaccine-protected monkeys were subsequently resistant to rechallenge infection at 12, 15, and 18 months after the first challenge, suggesting that a reasonable duration of protective immunity had been induced by the vaccine.

AIDS Vaccines↗
PubMed1993

Expression of Epstein-Barr-virus-related nuclear antigens and B-cell markers in lymphomas of SIV-immunosuppressed monkeys.

Simian-immunodeficiency-virus(SIV)-infected cynomolgus monkeys develop B-cell lymphomas in approximately one third of the cases. We have now studied the expression of cynomolgus-Epstein-Barr-virus(cyno-EBV) nuclear antigens in 13 cyno-EBV-carrying SIVsm-associated monkey lymphomas and established cell lines from 3 of these tumors. Immunoblots of cell lysates were probed with polyspecific and monospecific reagents directed against human EB-virus EBNAI-6, and against the membrane protein LMPI. An EBNA2-cross-reacting protein was demonstrated in 8 lymphoma tissues (8/13) and in the 3 cell lines derived from the tumors. All tumors expressed a polypeptide with 50 to 55 kDa molecular weight, which cross-reacted with some antibodies to EBNAI. Absorption experiments with normal monkey tissue showed that this polypeptide was specific for the cyno-EBV-carrying lymphoma cells. Equivalents of EBNA3-6 and LMPI could not be detected. Immunophenotypical characterization showed that the monkey lymphomas were similar to human HIV-associated B-cell lymphomas. Malignant B-cell lymphomas in experimentally SIVsm-infected cynomolgus monkeys can be a model for EBV-associated lymphomagenesis in immunodeficiency states.

Animals↗
PubMed1993

Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection.

Human immunodeficiency virus type 2 (HIV-2) has been reported to be less pathogenic than HIV-1. We have investigated the capacity of sera from nine HIV-2-infected individuals to neutralize their own autologous virus. All nine HIV-2-infected individuals neutralized autologous virus with titers ranging between 20 and 320. In contrast, we have previously reported that most HIV-1-infected individuals lack such antibodies. The difference between HIV-1 and HIV-2 infection was statistically significant (P < 0.0002, Pearson test) and the difference in neutralizing antibody prevalence may explain the faster disease progression in HIV-1-infected individuals than in HIV-2-infected individuals.

HIV Antibodies↗
PubMed1993

Autologous neutralizing antibodies to SIVsm in cynomolgus monkeys correlate to prognosis.

Sequential virus isolates from eight cynomolgus monkeys experimentally infected with SIVsm were studied for susceptibility to neutralization by autologous antibodies. The biological and antigenic characteristics of sequential reisolates differed both from the inoculum virus and from each other. Five monkeys developed neutralizing antibodies to the inoculum virus and the 12-day reisolate at 4 months postinfection, while the remaining three monkeys produced very little, if any, neutralizing antibodies. Strikingly, the two long survivor monkeys developed neutralizing antibody response to a second or third autologous reisolate and to 12 reisolates obtained from other monkeys. Thus the neutralizing antibody response of the long survivor monkeys showed a relatively broad specificity, whereas the neutralizing antibody response of the monkeys with early disease, if at all present, was specific for the infecting strain only and lost over time. Our results show that the pattern of virus neutralization in SIVsm-infected monkeys is similar to human immunodeficiency virus type 1-infected humans. In both cases, variant viruses resistant to neutralization by autologous sera emerge during the entire course of infection. In addition, the ability to produce autologous neutralizing antibodies to sequential virus reisolates appeared to correlate with the degree of immunodeficiency in the host.

Animals↗
PubMed1993

Incidence of HIV-1 infection among adults in the Kagera region of Tanzania.

The results of a population-based follow-up study are presented. The baseline study which started in August 1987, was carried out to determine the prevalence of human immunodeficiency virus (HIV-1) infection in the Kagera region of Tanzania. A multistage cluster sampling technique was adopted in the selection of the study population. In the follow-up survey which started in June 1988, members of the same study population were revisited and studied in order to determine the incidence of HIV-1 infection among those who were HIV seronegative in the initial survey. HIV serology was conducted by using enzyme-linked immunosorbent assay and all positive sera were confirmed by the Western blot technique. A total population of 1316 adults aged 15-54 years was studied, constituting an average follow-up response rate of 69% in the rural areas and of 59% in the urban area. The overall incidence of HIV-1 infection among the adult population sample was 13.7 per 1000 person-years at risk with the highest incidence in the urban zone (47.5 per 1000 person-years at risk) and the lowest incidence in one of the three rural zones (4.9 per 1000 person-years at risk). The age-specific annual incidence was highest in the age group 25-34 years for males and in the age group 15-24 for females. From these results it was estimated that the number of newly infected adults in the region each year is about 8200 with a range between 5400 and 11,000 corresponding to the 95% confidence limits on the overall incidence.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

HIV-antibody testings among injecting drug users (IDUs) in the Stockholm area, 1984-91: information compiled from testing laboratories.

The available information about testings for HIV antibodies in injecting drug users (IDUs) carried out in Stockholm between 1984 and 1992 has been compiled. These testings were carried out mainly in special settings. The use of codes (the first 2 digits giving the age and the last 4 the 6 and checking figures in the individual's personal identity number) precluded exact identification of individuals; in most cases, however, complementary information made it possible to recognize patients at follow-up. The data indicated that 9,150 persons associated with current or previous drug addiction were tested. The first extensive testings were performed in 1985 and 1986. After this period, 4,500 persons were retested. 11% of the IDUs tested in 1984-85 were found to be HIV-antibody-positive. After 1988, 1% were estimated to seroconvert each year. While in the first phase the heroin users predominated among those infected, in later years the rates of newly diagnosed infections became similar for all types of IDUs. The age profiles of the IDUs tested were similar up to 1988, after which there was an indication that also younger persons had entered the scene. However, the infected IDUs discovered belonged mainly to the 'old' cohort born between 1950 and 1960.

Adult↗
PubMed1993

HIV-1 and HIV-2 antibodies in pregnant women in the City of Maputo, Mozambique. A comparative study between 1982/1983 and 1990.

The seroprevalence of HIV-1 and HIV-2 among pregnant women in Maputo, the capital of Mozambique, was compared between the years 1982/83, 1988 and 1990. None of the 432 serum samples collected in 1982/83 was positive for HIV antibodies whereas in 1988 the HIV-1 and HIV-2 seroprevalence was 0.4% (2/500) and 0.6% (3/500), respectively, and in 1990 0.6% (12/2014) and 0.2% (4/2014), respectively. These results indicate that HIV infection has been introduced recently in Maputo and is spreading at a slow rate among women.

Adolescent↗
PubMed1993

Immunohistochemical distribution of leucocyte antigens in lymphoid tissues of cynomolgus monkeys (Macaca fascicularis).

Crossreactivity of antibodies to human leucocyte antigens with lymphoid tissues of cynomolgus monkeys was studied by immunohistochemistry and immunoblotting. Of a total of 54 clusters of differentiation (CD) antigens, 39 were expressed essentially with the same immunostaining patterns in the monkey as in human lymphoid tissues. By immunoblotting L26 (CD20) detected a 35 Kd molecule in the monkey lymph node. Our observations indicated that most of the CD antigens are expressed and can be studied in lymphoid tissues of cynomolgus monkeys.

Animals↗