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The efficacy of a recombinant human immunodeficiency virus (HIV) type 2 canarypox (ALVAC HIV-2) vaccine candidate given alone or in combination with HIV-2 envelope gp125 or HIV-2 V3 synthetic peptides was investigated in 14 cynomolgus monkeys. High antibody titers to HIV-2 gp125 were demonstrated in monkeys given booster immunizations with gp125. Neutralizing antibody titers were low (< or = 20) in all monkeys except 2. Significant lymphocyte proliferative responses to killed HIV-2 virions were observed in monkeys given booster immunizations with gp125. HIV-2-specific cytotoxic T lymphocytes were demonstrated prior to viral challenge in 3 of 12 monkeys. After challenge with homologous cell-free HIV-2 propagated in monkey cells, 4 of 10 monkeys immunized with ALVAC HIV-2 plus HIV-2 gp125 or V3 peptides were protected, as determined by negative virus isolation and polymerase chain reaction for viral DNA. Four monkeys immunized with ALVAC HIV-2 alone were not protected. All 12 control monkeys became infected. There was no correlation between the immunologic parameters studied and protection against infection in the vaccinated monkeys. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8+ T-cell antiviral factors (CAF) andβ-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-inducedβ-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also comparedin vitroCD8+ T-cell-mediated noncytotoxic antiviral activity againstβ-chemokine-sensitive R5 virus (HIV-1Bal) andβ-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specificβ-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8+ T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replicationin vitroin a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8+ T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients. [ABSTRACT FROM AUTHOR]

Cynomolgus macaques are frequently used in biomedical research. However, in contrast to their closest relative, the rhesus macaque, little is known about their Mhc genes except for the DQB1 locus. In this study, 33 DRB-sequences belonging to 17 allelic lineages were detected in a total of 68 macaques, 58 originating from Mauritius and 10 from China. The majority of the sequences were detected in the few macaques from China, confirming the low degree of genetic variation in macaques from Mauritius. In summary, the DRB region in cynomolgus macaques is polymorphic. The sequences belong in general to the same allelic lineages as in their closest relative, the rhesus macaque. Two exon 2 DNA sequences were identical in both species and may represent a trans-species origin. In addition, protein sequences of members of the DRB*W1 lineage seem to be rather conserved in the three macaque species examined so far. Six DRB-haplotypes were detected in the macaques from Mauritius. While single DRB-alleles or some protein sequences seemed to be conserved among macaque species, we could not detect any evidence for a trans-species conservation of a complete DRB region. Overall, the data indicate that reorganization of the DRB region by recombination is a major force in creating diversity in cynomolgus macaques as it is in rhesus macaques. [ABSTRACT FROM AUTHOR]

Background: No gold standard exists for diagnosis of HTLV infection. The aim of thus study was to compare the accuracy of a combination of two sensitive ELISAs with Western blot (WB), a line immunoassay, and PCR for diagnosis of HTLV infection.Study Design and Methods: Nine hundred eighty-five specimens were tested for the presence of HTLV antibodies by HTLV-I and/or HTLV-II EIAs (Murex and Ortho), WB (Diagnostic Biotechnology), line immunoassay (INNO-LIA, Innogenetics), and/or presence of HTLV DNA by PCR. The results were compared with the probable HTLV infection status of each subject, as determined by detailed review of all available laboratory, clinical, and epidemiologic data.Results: The sensitivity for diagnosis of HTLV-I infection was high for all assays evaluated, but both PCR and WB had a lower sensitivity rate (approx., 80%) for confirmation of HTLV-II. INNO-LIA detected 94 percent of the HTLV-II-positive samples. However, Murex EIA in combination with Ortho EIA was 100-percent sensitive for the detection of both HTLV-I and HTLV-II antibodies. Furthermore, the number of samples giving indeterminate results in the ELISA combination was much lower as compared with WB (2.5% vs. 50%).Conclusion: Based on these findings, a new, more sensitive and specific test strategy for HTLV diagnosis than the current algorithm, which includes WB, is proposed. Thereby, both the direct and indirect costs can be substantially reduced. [ABSTRACT FROM AUTHOR]

The cell-mediated immune response is likely to be important in controlling HIV/SIV infection. There is evidence that β-chemokines and other, as yet unknown, anti-viral factors play a role in host defence against HIV infection. We reported previously that HIV-2 exposed but seronegative cynomolgus macaques developed SIV-specific cytotoxic T lymphocytes and were resistant to mucosal SIV challenge. The aim of this study was to examine CD8+ cell-dependent production of β-chemokines and other anti-viral factors in these macaques. The animals, selected from among 17 monkeys enrolled in two separate experiments, were either treated with an anti-viral drug or immunized passively with HIV-2 antibody-positive serum. Three of these monkeys were protected against repeated HIV-2 challenge and were also able to control SIV infection 3 years later. Control samples were obtained from four macaques that became SIV infected and from 39 naïve animals. The three resistant monkeys showed significantly higher production of RANTES and MIP-1α than the 39 naïve animals. In addition, SIV infection was suppressed by CD8+ cell culture supernatants of these monkeys. However, antibodies to chemokines only partially neutralized CD8+ cell-mediated SIV suppression indicating that the anti-viral activity observed in these monkeys was the result of combined action of several inhibitory factors. [ABSTRACT FROM AUTHOR]

Binding to the surface of living E. histoyrica trophozoites of 125I-labelled anti-amoeba antibodies or of such antibodies and antiglobulin resulted in a rapid disappearance of the antibody into the medium. This disappearance consisted of a l temperature-independent and a subsequent slow temperature-dependent phase. The disappearance ot antibody from fixed trophozoites merely consisted of a temperature-independent rapid phase whereas no slow phase was observed. The magnitude of the rapid phase of antibody disappearance was virtually the same in living and fixed cells,During culture of living trophozoites For 4 h the amount of iodine-labelled material sedirnenting lighter than monomeric lgG increased from 2% to 14% of all labelled material in the case of the single antibody layer. The corresponding values fur the double layer were 2% and 32% Of the material lighter than lgG. 10% of that in the single layer anti 26"% of that in the double layer were detected in the medium. Thus. during the 4-h culture period 25% of the originally amoeba-bound single layer of antibody probably disappeared from she cells not complexed with antigen. 27%. disappeared as complexes heavier than IgG. 10% disappeared as material lighter than lgG. and 18% persisted on or within the cells. The corresponding values for the double layer antibody were 10%,30%, 26% and 34%. [ABSTRACT FROM AUTHOR]

The possible influence of cell membrane dynamics on complement activation and cytolysis was studied. The interaction between membrane-bound antibodies and complement was investigated by use of purified human C1q protein. The following observations were made: [1] Binding of C1q to cells was proportional to the amount of membrane-bound antibody. [2] Demonstration of C1q at the eel! surface was critically influenced by a prozone effect generated by the interaction between C1q and anti-C1q antibody. [3] C1q induced pronounced patching of membrane-bound antibody at 0°C and at 37°C, but its capping effect was weak. [4] C1q seemed to exert an inhibitory action on the disappearance of membrane-bound antibody. The antibody-bound C1q disappeared very rapidly from the cell membrane in comparison with the antibody. [5] The cytolytic sensitivity of several cell types differed at different stages of redistribution of membrane-bound antibody; maximal sensitivity corresponded to a predominantly patchy antibody distribution. Microfluorometry and the isotope antiglobulin method suggested that these changes in cytolytic sensitivity was due neither to differences in the amount of membrane-bound antibody nor to a different accessibility of membrane-bound antibody to complement. [ABSTRACT FROM AUTHOR]

All of 15 sera containing anti-mitochondrial antibodies (AMA), type M5, reacted in ELISA with ssDNA, whereas only four had anti-nuclear antibodies as demonstrated by immunofluorescence technique. Twelve of 15 had biological false-positive seroreaction for syphilis and seven of 11 cases investigated had a positive lupus anti-coagulant test. Cold agglutinins were present in 11 sera. Hyper-y-globulinaemia was not a prominent finding, but C4 values below the lower limit were common in spite of C3 within the normal range. Absorption of IgG fractions from three different sera with cardiolipin eliminated the reaction with ssDNA and mitochondria, supporting a certain degree of cross-reactivity among the antibodies. The presence of AMA, type M 5, seemed to discriminate a group of patients with symptoms often consistent with SLE although some of the most prominent findings were often absent. [ABSTRACT FROM AUTHOR]

The staining pattern of anti-actin sera on various cells smeared on glass was compared to the relative amount of cellular actin estimated by SDS-polyacrylamide-gel electrophoresis with subsequent scanning of the gel. Although the cells showed a varying stainability the actin content was fairly constant. Thus, the staining differences reflected changes in the organization of cellular actin rather than actual differences in the amount of actin. [ABSTRACT FROM AUTHOR]