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Biomedical subjects

B Vaslin

Publications and source records attributed to B Vaslin.

34 records · Page 2Linked to original sources
PubMed1995

Highly attenuated SIVmac142 is immunogenic but does not protect against SIVmac251 challenge.

We report here the use of the highly attenuated SIVmac142 clone, unable to establish permanent infection of rhesus macaques, in a vaccine trial. Four rhesus macaques were immunized over a long time period with HUT-78 cells infected with wild-type SIVmac142 or, in order to reinforce the safety use of the vaccine, a deleted mutant with similar in vitro infectivity. The first two injections were done with living cells and the remaining boosts with cells emulsified in muramyl dipeptide adjuvant. Three control macaques were injected with uninfected HUT-78 cells. Over 3 years, we have been unable except once to detect viral infections by three methods. However, antibodies directed against the viral Gag proteins and envelope glycoproteins were detected by immunoblots and/or in vitro neutralization assays. All macaques were challenged intravenously with a low dose (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251 grown on macaque PBMCs. All seven animals became persistently viremic following challenge. The cell-associated viral loads of the vaccinated monkeys were not reduced relative to those of unvaccinated controls during the first weeks postchallenge even if vaccinated monkeys did not present a transient CD4 decrease. Thus, our data reinforced the notion that the efficacy of live attenuated SIV requires the establishment of persistent infection.

Animals↗
PubMed1995

Functional consequences of macrophage infection by human immunodeficiency virus: bispecific antibody targeting of HIV-1-infected cells to Fc gamma RI expressing effector cells.

Human monocytes/macrophages play a major role in pathogenesis of human immunodeficiency virus (HIV) infection. These cells have been suspected of acting as a reservoir for the virus and are important in viral dissemination and persistence in infected individual. Furthermore, several biologic and clinical features indicate that monocytes/macrophages from HIV-1-seropositive patients have characteristics of an activation status, including the ability to secrete high levels of cytokines. Dysregulation of the cytokine network may influence the level and the consequences of viral replication in infected monocytes/macrophages. Therefore, the development of virus-specific agents that may interfere with viral replication could help to slow down the fatal course of HIV infection. In this article, we try to further quantify the early and late kinetic patterns of the cytokine network during HIV-1 macrophage infection and report the biologic effects of virus-specific bispecific antibody (MDX-240) in HIV-1 macrophage infection.

Antibodies, Bispecific↗
PubMed1995

Tumor necrosis factor-alpha in serum of macaques during SIVmac251 acute infection.

TNF secretion was explored in sera during acute SIV-infection of cynomolgus macaques. A peak of TNF was detected in sera of animals in concomitance with SIV replication. Likewise, AZT treatment delayed and reduced peaks of viral replication and TNF production. Thus, SIVmac251-infected monkey could be an excellent model to explore the interdigitation existing between HIV and TNF in acute and chronic infection and to develop new therapeutic strategies that target the production of this cytokine or its inductive effects.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Four cross-linked HIV Gag peptides prime the immune response to HIV proteins in mice.

The functional help provided by four cross-linked synthetic peptides from HIV-1 Gag structural proteins was investigated in the mouse model. These peptides, selected upon non-self-criteria, are not predicted as T epitopes by classical prediction methods such as the Rothbard consensus or the amphipathy rule. Priming mice with these peptides allows the enhancement of the antibody response to HIV-1 Gag proteins (p55, p18, p24) given in the viral particle form. Furthermore, all of them also induce spleen and lymph node cells from primed mice to proliferate in vitro, in a MHC class II restricted context. This approach may help to identify relevant immunogenic viral epitopes that may be involved in a vaccinal strategy.

Amino Acid Sequence↗
PubMed1994

Induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection?

In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of SIV/Delta B670 in either an oil-in-water emulsion with Ribi Detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL) (group A) or a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). Animals were challenged with 10-100 monkey ID50 of monkey-cell-grown SIVmac251 3 months after the last injection, along with a group of four unvaccinated controls. Group B animals demonstrated the strongest immune responses following immunization, including neutralizing antibody titres against the challenge virus ranging from 160 to 320 and SIV-specific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL-2) production responses to the immunogen. Neutralizing antibody was not detectable in group A animals, ELISA titres were lower (10(2)-10(4)), no in vitro lymphoproliferative responses were observed, and in vitro IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a more pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degree of lymphadenopathy on day 7, followed by hypothermia and generally higher levels of serum viraemia on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nef and Gag synthetic peptide priming of antibody responses to HIV type 1 antigens in mice and primates.

T epitope mapping in human immunodeficiency virus proteins provides a useful tool for AIDS vaccine design. We have previously shown that four peptides selected from the Gag polyprotein of HIV-1 were able to prime mice for in vitro lymphoproliferative responses. These responses were shown to be MHC restricted, and a pool of these peptides was able to prime mice for a subsequent humoral response to HIV-1 Gag proteins. Here we show that two of these Gag peptides are able to prime the anti-HIV-1 IgG response to heat-inactivated HIV-1 in B10Sc.Cr mice. Furthermore, we extended this study in the nonhuman primate model, and show efficient priming of the IgG response to heat-inactivated HIV-1 using the pool of four Gag peptides in baboons. Further mapping of "nonself" peptides is extended to the HIV-1 Nef protein. Three potential Nef T epitopes located at positions 137-145, 98-107, and 81-95 are also shown to prime the IgG response to HIV-1 in the mouse model, although T cell proliferation to recall peptides in vitro was not detectable. Although they have not yet been defined as major helper T epitopes in humans, using classic in vitro stimulation assays, the fact that most of them are able to prime IgG responses in animals without detectable in vitro proliferative responses does not rule out their functional helper capacity in humans.

Amino Acid Sequence↗
PubMed1994

An animal model for antilentiviral therapy: effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus.

We analyzed the kinetics of the virological and immunological events that occurred in four AZT-treated cynomolgus macaques during the acute infection that followed their exposure to the simian immunodeficiency virus (SIVmac251) grown on monkey PBMCs in a cell-free stock solution. These events included changes in the CD4+ and CD8+ T lymphocyte subsets, p27 antigenemia, infectious serum virus, and cell-associated virus loads. The kinetics of these changes proved strikingly similar to those reported in human HIV-1 infection. Four other SIV-exposed macaques were treated with placebo instead of AZT. We demonstrated that AZT does not prevent SIV infection, even when administered before SIV inoculation. However, the peaks of p27 antigenemia and of serum and cellular viremia were significantly smaller and occurred significantly later in the monkeys given AZT than in those given placebo.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Antibody-dependent cellular cytotoxicity and neutralization of human immunodeficiency virus type 1 by high affinity cross-linking of gp41 to human macrophage Fc IgG receptor using bispecific antibody.

Human monocytes/macrophages, which express Fc receptors for IgG are involved in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis. These receptors are known to mediate numerous immunological functions including cell-mediated killing and possibly targeting of HIV to the lysophagosome monocyte-derived macrophage (MDM) entry route for virus neutralization. To study both activities in HIV-1 infection, MDM Fc gamma RI was specifically selected using bispecific antibody (Bs-Ab) containing whole human monoclonal antibody against gp41 and the Fab' fragment of murine anti-Fc gamma RI 22.2 antibody. Bs-Ab was found to mediate potent antibody-dependent cellular cytotoxicity and virus neutralization.

Antibodies, Bispecific↗
PubMed1994

Evolution of the human immunodeficiency virus type 2 envelope gene in preimmunized and persistently infected rhesus macaques.

The V3 and V4 domains of human immunodeficiency virus type 2 (HIV-2) env genes from 14 rhesus macaques experimentally infected by HIV-2 SBL6669/H5 were sequenced. No variation was observed in viral sequences from sera and from uncultured peripheral blood mononuclear cells during primary infection. The first mutations were detected 17 months after infection; they mainly concerned the region between the V3 and V4 domains and not those domains themselves, which are known to be hypervariable, suggesting that variation of V3 is a late event of HIV infection.

AIDS Vaccines↗
PubMed1992

Specific and non-specific immunity and protection of macaques against SIV infection.

The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge.

Animals↗
PubMed1988

Inactivation of human immunodeficiency virus during human growth hormone production.

Since human immunodeficiency virus (HIV) has been found in the brains of AIDS patients, the possibility was investigated that preparations of human growth hormone (hGH) extracted from human pituitary glands harbor infectious HIV. It was found that the procedure used for extracting hGH, i.e. a combination of acid pH and 10% ethanol, totally inactivates HIV infectivity.

Antiviral Agents↗
PubMedDate not supplied

Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251.

We developed an animal model for the male-to-female transmission of human immunodeficiency virus, consisting of an atraumatic vaginal application of simian immunodeficiency virus onto the intact vaginal mucosa of cynomolgus macaques. Different doses of a pathogenic isolate of SIVmac251, with or without seminal plasma, were infused into the vaginas of female macaques. Infection of macaques could be achieved after a single exposure to the virus. Two patterns of infection were underscored with no relation to the virus dose inoculated: in 50% of the monkeys, SIV was persistently recovered and a strong antibody response to SIV was evidenced in blood and vaginal secretions. In the other infected animals, SIV infection was only transiently evidenced and a weak systemic antibody response was detected. It appeared that the presence of seminal plasma may be implicated in this variability only when low doses of virus are inoculated. Sequence analysis of the env gene of SIV revealed that most of the persistently viraemic animals were infected with a viral variant different from that of transiently viraemic macaques.

Amino Acid Sequence↗
PubMedDate not supplied

Consequences of ddI-induced reduction of acute SIVmac251 virus load on cytokine profiles in cynomolgus macaques.

This study evaluates the consequences of antiretroviral treatment of the acute simian immunodeficiency virus (SIV) primary infection on virus load and cytokine responses. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate (SIVmac251). Animals were pretreated with 10.8 mg/kg/day of dideoxyinosine (ddI) from 4 days before inoculation, and treatment was continued for 28 days. Proinflammatory (IL6, IL1 beta and TNF alpha) and antiinflammatory (IL10) cytokine and lymphokine (IL2, IL4 and IFN gamma) polymerase chain reaction (PCR) ratios were monitored in unmanipulated peripheral blood mononuclear cells (PBMCs) during acute infection by using a semiquantitative reverse transcription (RT)-PCR method. PBMC-associated virus loads were dramatically reduced compared to those of placebo-treated macaques. Nevertheless, a transient rise in IL6, IL1 beta, TNF alpha and IL10 mRNA expression was observed in PBMCs. IL2, IL4 and IFN gamma mRNAs were either undetectable or weakly detectable throughout the study, with no major changes. Despite a dramatic reduction in the acute viral loads in ddI-treated monkeys, early cytokine mRNA profiles were comparable to those of untreated SIVmac251-infected monkeys. Contrary to what was previously evidenced during primary infection with an attenuated SIV clone, no increase in IL2 and IL4 mRNA was detected in PBMCs of the ddI-treated monkeys, although these monkeys exhibited virus loads similar to those evidenced in macaques infected by attenuated SIV. These data indicate that differential lymphokine expression patterns found in pathogenic and Nef-truncated SIV-infected monkeys may not be strictly dependent on virus load levels.

Acute Disease↗
PubMedDate not supplied

Chemoattractant factors (IP-10, MIP-1alpha, IL-16) mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques.

We have used semiquantitative RT-PCR to monitor the expression of mRNA encoding chemoattractant factors IP-10, MIP-1alpha, and IL-16 in freshly isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral replication (two weeks after experimental inoculation) and proinflammatory cytokine IL-6 mRNA expression, high levels of MIP-1alpha and IP-10 mRNA were produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked progressive overexpression of IFN-gamma mRNA coinciding with an increase in the CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL-16 mRNA. Our results suggest the role of chemokines IP-10, MIP-1alpha, and IL-16 in the development of inflammatory and immune responses during the early stages of lentiviral infection.

Animals↗