Biomedical subjects

R Thorstensson

Publications and source records attributed to R Thorstensson.

At least 19 recordsLinked to original sources

PubMed2006

Multicenter evaluation of a new 4th generation HIV screening assay Elecsys HIV combi.

Fourth-generation screening assays which permit a simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody reduce the diagnostic window on average by four days in comparison to third-generation antibody assays. Recently, the new automated Elecsys HIV combi was compared in a multicenter study to alternative fourth- and third-generation assays, p24 antigen test and HIV-1 RNA RT-PCR. A total of 104 serocon-version panels, samples of the acute phase of infection after seroconversion (n = 33), anti-HIV-1 positive specimens (n = 572) from patients in different stages of the disease, 535 subtyped samples from different geographical locations, including group M (subtypes A-J) and group O, anti-HIV-2 positive sera (n = 364), dilutions of cell culture supernatants (n = 60) infected with different HIV-1 subtypes, selected performance panels, 8406 unselected samples from blood donors originating from different blood transfusion centers, 3810 unselected sera from daily routine and from hospitalized patients, 9927 unselected samples from South Africa and 1943 potentially interfering samples were tested with the Elecsys HIV combi. Elecsys HIV combi showed a comparable sensitivity to HIV-1 Ag stand-alone assays for early detection of HIV infection in seroconversion panels. The mean time delay of Elecsys HIV combi (last negative sample + 1 day) in comparison to HIV-1 RT-PCR for 92 panels tested with both methods was 3.23 days. The diagnostic window was reduced with Elecsys HIV combi between 1.56 and 5.32 days in comparison to third-generation assays. The specificity of Elecsys HIV combi in blood donors was 99.80% after repeated testing. Our results show that a fourth-generation assay with improved specificity and sensitivity like the Elecsys HIV combi is suitable for blood donor screening due to its low number of false positives and since it detects HIV p24 antigen with a comparable sensitivity to single antigen assays.

Early Diagnosis↗

PubMed2005

Antigen-specific beta-chemokine production and CD8 T-cell noncytotoxic antiviral activity in HIV-2-infected individuals.

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) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8+ T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1Bal) and beta-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-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 replication in vitro in 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.

Adult↗

PubMed2005

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau.

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.

Adolescent↗

PubMed2004

Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen.

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.

Animals↗

PubMed2004

MhcDRB-sequences from cynomolgus macaques (Macaca fascicularis) of different origin.

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.

Amino Acid Sequence↗

PubMed2004

Ethical issues in research on control of the HIV/AIDS epidemic: report from a workshop of the world federation of scientists, Erice, Sicily, Italy, 22-24 August 2003.

In research on control of the HIV/AIDS epidemic there are many ethical issues to be considered. The problem of personal autonomy versus the interest of society to prevent the spread of the disease in various settings makes it difficult to follow the regulations of the Declaration of Helsinki in all respects. This is particularly clear in the evaluation of trials aimed at preventing mother-to-child transmission of HIV. The interest of the child does not always conform to the policy of avoiding stigmatization of the mother. Programmes for the implementation of antiretroviral therapy and vaccine trials may differ in countries with different mean incomes of the inhabitants, and are also influenced by local patterns. For this reason, the Declaration of Helsinki should be changed in such a way that it conforms with the ways in which it may be possible to combat such a disastrous epidemic as that caused by HIV.

Developing Countries↗

PubMed2003

Development and evaluation of a flow-cytometric assay of specific cell-mediated immune response in activated whole blood for the detection of cell-mediated immunity against varicella-zoster virus.

A new assay for the detection of specific cell-mediated immune (CMI) responses is described. Whole blood, diluted 1/10 in medium, was cultured in the presence or the absence of specific antigens. Results were assessed by flow cytometric analysis with or without immunophenotyping to detect proliferating lymphoblasts among cultured cells. Interferon-gamma, IL-10, and IL-5 in culture supernatants are measured by ELISAs. The assay was evaluated using samples from 37 VZV-antibody-positive children with a history of chickenpox and samples from 15 seronegative children without a history of chickenpox; it displayed a sensitivity of 95% and a specificity of 100% for the detection of varicella-zoster virus (VZV)-specific CMI. The intraassay and interassay variations of the new test were lower than with the conventional assay for CMI, detecting thymidine incorporation in peripheral blood mononuclear cells (PBMCs). Cytokines were detected in only 70% of cultures from VZV-antibody-positive subjects. The cytokine response was restricted to IFN-gamma in most cases. The Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA) is a precise and accurate yet simple and convenient test that can be readily employed for the examination of single samples as well as for large-scale studies.

Adolescent↗

PubMed2003

Reduction of the diagnostic window in three cases of human immunodeficiency-1 subtype E primary infection with fourth-generation HIV screening assays.

BACKGROUND AND OBJECTIVES: The influence of genetic variability on the sensitivity of serological diagnosis of human immunodeficiency virus (HIV) infection has, to date, been poorly investigated. The aim of the present study was to assess whether fourth-generation assays for the combined detection of HIV antigen and antibodies to HIV (anti-HIV) permit a reduction of the diagnostic window in comparison to third-generation antibody enzyme immunoassays (EIAs), which so far have shown a poor sensitivity for detection of HIV-1 non-subtype B primary infections. MATERIALS AND METHODS: Three patients with primary HIV-1 subtype E (CRF01-AE) infection were tested with different third- and fourth-generation assays, stand-alone HIV antigen (Ag) EIAs and reverse transcription-polymerase chain reaction (RT-PCR). Additionally, virus lysates from HIV-1 Group M and O and HIV-2, at concentrations of p24 Ag close to the detection limit of licensed HIV Ag EIAs, were investigated with fourth-generation EIAs and HIV Ag EIAs. RESULTS: In the first blood donor, the most sensitive fourth-generation assay detected HIV-1 infection 11 days earlier than five of the eight third-generation antibody assays. Fourth-generation EIAs, with a high sensitivity for HIV antigen, detected HIV-1 subtype E infection simultaneously or 4 days later than HIV-1 RT-PCR on pooled samples. Low concentrations of virus lysates of different HIV-1 subtypes A-H and group O, tested positive with fourth-generation EIAs, with a high sensitivity of the antigen-detection module. CONCLUSIONS: Fourth-generation EIAs, especially those with a high sensitivity for HIV-1 p24 antigen, reduce the diagnostic window for primary HIV-1 subtype E infection in comparison with third-generation antibody-screening assays. These preliminary data from seroconversions and virus lysates indicate that the genetic diversity of HIV-1 does not represent a major challenge for the most sensitive EIAs of this new assay generation.

Antigenic Variation↗

PubMed2002

Spontaneous production of RANTES and antigen-specific IFN-gamma production in macaques vaccinated with SHIV-4 correlates with protection against SIVsm challenge.

The beta-chemokines, RANTES, MIP-1alpha and MIP-1beta, have been implicated as being some of the protective factors in the immune response against human immunodeficiency virus (HIV) infection. We have presented data previously indicating that these chemokines also play a role in protective immunity against HIV/SIV infection in macaques. The aim of this study was to investigate the production of beta-chemokines in eight cynomolgus macaques vaccinated with non-pathogenic SHIV-4 in relation to protection against pathogenic SIVsm challenge. Four control animals were also included in the study. Two of the vaccinated monkeys were completely protected and one was partially protected against the challenge virus. The monkeys that resisted infectious SIVsm virus challenge showed higher spontaneous beta-chemokine production by peripheral blood mononuclear cells and had higher numbers of antigen-induced IFN-gamma secreting cells compared to the non-protected animals. Our observations support our previous findings that the genetic background of the host and/or environmental factors are involved in the chemokine production and that beta-chemokines contribute to protection against HIV/SIV infection.

Animals↗

PubMed2001

Coreceptor usage of sequential isolates from cynomolgus monkeys experimentally Infected with simian immunodeficiency virus (SIVsm).

Sequential isolates from eight cynomolgus monkeys experimentally infected with simian immunodeficiency virus (SIVsm, of sooty mangabey origin) were tested for coreceptor use in the human osteosarcoma indicator cell line, GHOST(3), expressing CD4 and one or another of the chemokine receptors CCR3, CCR5, CXCR4, BOB, or the orphan receptor Bonzo. The indicator cell line carries the human immunodeficiency virus type 2 long terminal repeat-driven green fluorescence protein gene that becomes activated upon infection with HIV or SIV and fluorescence can be quantitated by flow cytometric analysis. The methodological details are described in the accompanying paper (Vödrös et al., 2001, Virology 290, in press). All SIVsm inoculum viruses and reisolates used CCR5 with a high level of efficiency. CCR5 use was stable over time. BOB and Bonzo use was less efficient than CCR5 use and, in particular, late isolates obtained at the time of immunodeficiency varied greatly in their coreceptor use and often could not establish a productive infection in BOB- or Bonzo-expressing cells. Unexpectedly, early reisolates obtained 12 days postinfection could infect the entire GHOST(3) panel including the parental cells. In one case this was due to use of CXCR4, either transfected or endogenously expressed on the GHOST(3) cells. Our results demonstrate the complex coreceptor use of SIVsm isolates. Moreover, they focus attention on the initial phase of virus replication when the availability of target cells may govern the replication pattern of the virus.

Animals↗

PubMed2001

Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki Forest virus and boosting with modified vaccinia virus Ankara.

The immunogenicity of two vector-based vaccines, either given alone or in a prime-boost regimen, was investigated. Cynomolgus macaques were immunised with modified vaccinia virus Ankara (MVA) expressing simian immunodeficiency virus (SIV)macJ5 env, gag-pol, nef, rev, and tat genes (MVA-SIVmac) or primed with a Semliki forest virus (SFV) vaccine expressing the same genes (SFV-SIVmac) and boosted with MVA-SIVmac. Generally, antibody responses, T-cell proliferative responses and cytotoxic T-cell responses remained low or undetectable in vaccinees receiving MVA-SIVmac or SFV-SIVmac alone. In contrast, monkeys who first received SFV-SIVmac twice and then were boosted with MVA-SIVmac showed increased antibody responses as well as high T-cell proliferative responses. Three of these vaccinees had cytotoxic T-lymphocytes directed against three or four of the gene products. No evidence of protection was seen against an intrarectal heterologous SIVsm challenge given 3 months after the last immunisation. The study demonstrates a prime-boost strategy that efficiently induces both humoral and cellular immune responses.

AIDS Vaccines↗

PubMed2001

Role of CD8+ cell-produced anti-viral factors in protective immunity in HIV-2-exposed but seronegative macaques resistant to intrarectal SIVsm challenge.

The cell-mediated immune response is likely to be important in controlling HIV/SIV infection. There is evidence that beta-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 beta-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-1alpha 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.

Animals↗

PubMed2000

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure. Karolinska Institute Primary HIV Infection Study Group.

OBJECTIVE: To determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the 'window period' and the influence of early initiated antiretroviral treatment (ART). DESIGN: A prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0-23) days after the onset of symptoms in 10 patients. MAIN OUTCOME MEASURES: The time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. RESULTS: The illness appeared 13-15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1-2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2-7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. CONCLUSION: Many tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.

Follow-Up Studies↗

PubMed2000

Cell-mediated immunity to low doses of SIVsm in cynomolgus macaques did not confer protection against mucosal rechallenge.

Simian immunodeficiency virus (SIV) infection of macaques is a useful model for studies of the roles of different immune responses against viruses that cause (AIDS). In this study, six cynomolgus macaques were inoculated intrarectally with subinfectious or infectious doses of SIVsm to assess the SIV specific immunity, in particular protective immunity against subsequent challenge with a higher dose of SIVsm. Following the first inoculation with SIVsm, the two monkeys given the highest doses of cell-free SIVsm stock and one monkey given the intermediate dose became infected. In the three remaining animals, one animal inoculated with an intermediate dose and two animals given low doses of SIVsm, no overt infection occurred. Nevertheless, SIV specific cytotoxic T-cells against Gag/Pol and Nef proteins and T-cell proliferative responses against HIV-2 whole viral lysate, native HIV-2 gp125, recombinant SIV gp140 and SIV Env synthetic peptides were detected. After intrarectal rechallenge of the uninfected macaques with a higher dose of SIVsm all the animals became infected. These results demonstrate that cell mediated immunity can occur in the absence of detectable infection in monkeys inoculated with a low dose of SIVsm. Despite the presence of cellular immune responses, the animals were not protected when challenged with a higher dose of virus later.

Administration, Rectal↗

PubMed2000

Shortening of the diagnostic window with a new combined HIV p24 antigen and anti-HIV-1/2/O screening test.

Because antibodies to the human immunodeficiency virus (HIV) are absent in the very early phase of HIV infection, there remains a slight residual risk for HIV transmission by blood donations by viremic but antibody negative donations. To shorten the diagnostic window between infection and the detection of antibodies, Enzygnost HIV Integral (Dade Behring, Germany) was developed. With this new test, HIV p24 antigen and HIV antibodies can be detected simultaneously in a single test. In a multicenter study the new screening assay has been compared with various tests that detect only HIV antibodies or HIV p24 antigen and with assays which permit a simultaneous detection of HIV antigen and HIV antibodies. The new assay showed 100% sensitivity for the detection of antibodies to HIV-1, groups M (n=1102) and O (n=55), and HIV-2 (n=289). In 23 out of 52 seroconversion panels, seroconversion was detected 2-18 days earlier with the new combined antigen/antibody test compared to single antibody tests. All samples from a viral load panel (n=451), all samples containing p24 antigen (n=302), and all but one of the cell culture supernatants (n=38) infected with various HIV-1 subtypes or HIV-2 were identified reliably by the new test. The specificity of the assay for 4002 unselected blood donors was 99.78% initially and 99.80% after retesting. Potentially interfering factors had no systematic influence on specificity. By testing for p24 antigen, which is present prior to the onset of antibody production in some cases of recent HIV infection, the new assay reduces the diagnostic window as compared to third generation screening assays, thus permitting an earlier diagnosis of HIV infection.

AIDS Serodiagnosis↗

PubMed1999

Fine characterization of a V3-region neutralizing epitope in human immunodeficiency virus type 2.

We have previously identified two distinct antigenic sites in the third variable region (V3) of human immunodeficiency virus type 2 (HIV-2) corresponding to the principal neutralizing determinant (PND) of HIV-1, the conserved Phe-His-Ser-Gln and Trp-Cys-Arg motifs (positions 315-318 and 329-331), which possibly interact to form a discontinuous antigenic site. The aim of this study was to further identify and characterize the immunogenic sites in the V3-loop of HIV-2 that are important in the binding of neutralizing antibodies and to study in detail the importance of different configurations of peptides corresponding to this region. Peptides representing modifications of the V3-region of HIV-2(SBL6669-ISY) were used for immunization of guinea pigs. With one exception, both the Phe-His-Ser-Gln and the Trp-Cys-Arg motifs were required in the peptide sequences to obtain neutralizing hyperimmune guinea pig sera, and the highest titers were obtained after immunization with 20-27 amino acids (aa) long peptides. Neither substitutions nor deletions of residues between the two motifs, nor the addition of peptide sequences representing a T-helper epitope improved the induction of neutralizing antibodies. Computer simulation modeling revealed that the Phe-315, His-316, Trp-329 and Cys-330 are likely to participate in the formation of a discontinuous epitope. Taken together, these data support the hypothesis that the well conserved motifs FHSQ (positions 315-318) and WCR (positions 329-331) of the HIV-2(SBL6669) V3 region are important targets for neutralizing antibodies, and this may have implications for the design of a future HIV-2 vaccine.

Amino Acid Motifs↗

PubMed1999

Comparative evaluation of 14 immunoassays for detection of antibodies to the human T-lymphotropic virus types I and II using panels of sera from Sweden and West Africa.

BACKGROUND: A new generation of assays for the detection of human T-lymphotropic virus types I and II (HTLV-I/II) antibodies has been released. These assays incorporate HTLV-I- and HTLV-II-specific antigens, and some are based on new assay principles. Comparative evaluation data that include these new as well as previous assays are limited. STUDY DESIGN AND METHODS: Fourteen HTLV antibody assays were evaluated by using well-characterized panels of sera from Guinea-Bissau, West Africa, and Sweden. The sera included 127 HTLV-I-positive and 62 HTLV-II-positive specimens, as well as 919 consecutive negative samples. RESULTS: The sensitivity for HTLV-I was 100 percent for all assays, except one, which repeatedly missed one sample. The sensitivity for HTLV-II varied between 86 percent and 100 percent. In general, new-generation assays incorporating HTLV-II-specific antigens, and some of which are based on new assay principles, had a higher sensitivity for HTLV-II than previous assays, which mainly are based on HTLV-I antigens. The specificity was generally higher for new assays than for the previous versions. Testing of Swedish blood donor sera gave higher specificities (94-100%) than did that of African specimens (90-99.7%). Most assays had low delta values (DVs), although there was a tendency toward increased DVs for the new generation of assays. Only two of the new generation of assays came close to a combination of high sensitivity for both HTLV-I and HTLV-II, high specificity, positive and negative predictive values, and high DVs. CONCLUSION: The sensitivity for HTLV-I was generally high and appears to have improved for HTLV-II with the introduction of a new generation of assays incorporating HTLV-II-specific antigens. However, some assays still give false-negative results on HTLV-II-positive specimens. The specificities and the DVs were generally higher for the new assays than for the previous versions.

Africa, Western↗

PubMed1999

Characterization of neutralizing sites in the second variable and fourth variable region in gp125 and a conserved region in gp36 of human immunodeficiency virus type 2.

Several determinants of human immunodeficiency virus (HIV) have been suggested to harbor sites important for neutralization. The third variable region (V3) of the envelope glycoprotein (gp) is an important neutralizing determinant for both serotypes of HIV. The localization of additional neutralizing regions is an urgent task because the virus appears to mutate to phenotypes that escape neutralizing antibodies. Therefore, we have focused on the possibility of finding other immunodominant regions in the envelope glycoproteins of human immunodeficiency virus type 2 (HIV-2). By immunization of guinea pigs with peptides corresponding to different selected regions of gp125 and gp36, we have found three antigenic determinants located in the V2 and V4 regions of the envelope protein gp125, and one region in the glycoprotein gp36, which are important for human antibody binding and also as targets for neutralization. The peptide representing the V2 region had the most pronounced capacity to induce neutralizing anti-HIV-2 antibodies in guinea pigs. Neutralizing activity was also detected in an antipeptide guinea pig sera representing a linear site in gp36, amino acids 644-658. A substitution set of peptides representing the conserved antigenic site in the central part of gp36 was used to identify the role of individual amino acids important for human antibody binding.

Amino Acid Sequence↗