Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm.

Objective: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2.

Design And Methods: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa.

Immune responses but no protection against SHIV by gene-gun delivery of HIV-1 DNA followed by recombinant subunit protein boosts.

The efficacy of combining immunization with human immunodeficiency vitus type 1 (HIV-1) DNA and HIV-1 recombinant proteins to obtain protection from chimeric simian/human immunodeficiency virus (SHIV) was determined. Four cynomolgus monkeys received four gene-gun immunizations intraepidermally of plasmid DNA encoding HIV-1lai env (gp160), gag, tat, nef, and rev proteins. Ten micrograms of DNA was used per immunization.

Outcome of immunization of cynomolgus monkeys with recombinant Semliki Forest virus encoding human immunodeficiency virus type 1 envelope protein and challenge with a high dose of SHIV-4 virus.

Infection of macaques with chimeric simian-human immunodeficiency viruses (SHIVs) allows evaluation of HIV-1 envelope vaccines. SHIV-4 is based on SIVmac239 but carries the env, tat, and rev genes of HIV-1IIIB. In this study we used Semliki Forest virus (SFV) RNA vectors to express the envelope protein gp160 of HIV-1IIIB in cynomolgus macaques.

Protection of human immunodeficiency virus type 2-exposed seronegative macaques from mucosal simian immunodeficiency virus transmission.

At present it is not known which form of immunity would be most effective against infection with human immunodeficiency virus (HIV). To evaluate the possible role of cellular immunity, we examined whether four HIV type 2-exposed but seronegative macaques developed cellular immune responses and determined whether these exposed macaques were resistant to mucosal transmission of simian immunodeficiency virus (SIV). Following intrarectal challenge with SIV, 2 monkeys were protected against detectable SIV replication and another showed suppressed viral replication compared to 14 persistently infected controls.

Prevention of simian immunodeficiency virus, SIVsm, or HIV-2 infection in cynomolgus monkeys by pre- and postexposure administration of BEA-005.

Objective: To study the possibilities and limitations of postexposure treatment to prevent the establishment of infection after accidental exposure to HIV.

Design And Methods: The effect of 2,3'-dideoxy-3'-hydroxymethyl cytidine (B1 A-005) was investigated on acute simian immunodeficiency virus (SIV) and HIV-2 infections in macaques in pre- and postexposure treatment experiments.

Results: Postexposure treatment with BLA-005 (3 x 10 mg/kg) for as short as 3 days prevented infection with SIVsm after intravenous or rectal inoculation.

Immunogenicity and protective efficacy of a human immunodeficiency virus type 2 recombinant canarypox (ALVAC) vaccine candidate in cynomolgus monkeys.

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.

Protection against mucosal SIVsm challenge in macaques infected with a chimeric SIV that expresses HIV type 1 envelope.

In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge. Four cynomolgus monkeys were inoculated intravenously with SHIV-4. Virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of SHIV.

Broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections.

Sera from human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2)-infected humans were tested with autologous (from the same individual) and heterologous (from other individuals) virus isolates in a neutralization assay. Similarly, sera from experimentally simian immunodeficiency virus (SIVsm from sooty mangabey) or HIV-2SBL6669-infected cynomolgus macaques were tested for neutralizing activity against autologous and heterologous reisolates. In the neutralization assay, the virus dose ranged between 10-75 50% infectious dose (ID50), sera were used in five 2- or 4-fold dilutions, beginning with 1:20, and human peripheral blood mononuclear cells (PBMCs) served as target cells.

SIV infection of monkey spleen cells including follicular dendritic cells in different stages of disease.

Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes, and macrophages from SIVsm-inoculated cynomolgus monkeys (Macaca fascicularis) at different stages of disease were compared for latent and productive SIV infection. Analysis of FDCs by in situ hybridization, electron microscopy, and coculture assays indicated that comparatively high levels of virus were associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR results revealed that the levels for SIVpol DNA did not correlate with the level of env mRNA in the various cell subsets, suggesting differences in latency.

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.

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.

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.

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.

Chimeric macaque/human Fab molecules neutralize simian immunodeficiency virus.

A collection of simian immunodeficiency virus (SIV) neutralizing recombinant Fab fragments was generated using the combinatorial antibody library approach. Functional antibody fragments efficiently expressed in Escherichia coli were identified only in the form of chimeric macaque heavy chain gamma 1 and human light chain kappa. The gamma 1 and kappa chains were derived from a clinically healthy long-term surviving SIVsm-infected cynomolgus macaque and from an asymptomatic HIV-2 seropositive individual, respectively.

Heterologous HIV-2 challenge of rhesus monkeys immunized with recombinant vaccinia viruses and purified recombinant HIV-2 proteins.

In an attempt to analyse the role of anti-envelope immunity in the protection of rhesus monkeys against an HIV-2 intravenous challenge, rhesus macaques were immunized twice with recombinant HIV-2 ROD vaccinia viruses (10(8) p.f.u.

Broadly reactive HIV-2 and SIVmac specific antibody-dependent cellular cytotoxicity in immunized and infected cynomolgus monkeys.

Antibody-dependent cellular cytotoxicity (ADCC) was analysed in groups of cynomolgus monkeys that had been immunized with either HIV-2 (strains SBL6669 or SBL-K135) or SIVmac. HIV-2- and SIVmac-infected monkeys were also studied for ADCC. Sequential serum samples were collected from the animals, which were followed for 1 to 3 years.

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.

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.

Efficacy of inactivated whole HIV-2 vaccines with various adjuvants in cynomolgus monkeys.

Twenty-one cynomolgus monkeys were immunized with whole inactivated HIV-2 preparations administered with various adjuvants (incomplete Freund's adjuvant, Alum, Ribi, MDP, or Iscoms) and challenged with 10 or 100 MID50 of a homologous monkey-cell grown, cell-free HIV-2. Seven animals were completely protected against infection, three showed reduced virus replication. The vaccines elicited neutralizing and ADCC antibodies; the titers did not correlate with protection.

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.

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.

Protection of cynomolgus macaques (Macaca fascicularis) against infection with the human immunodeficiency virus type 2 strain ben (HIV-2ben) by immunization with the virion-derived envelope glycoprotein gp130.

We have investigated the efficiency of a subunit vaccine consisting of native gp130 micelles of HIV-2ben mixed with keyhole limpet hemocyanin (KLH). Over a period of 52 weeks, nine cynomolgus monkeys (Macaca fascicularis) were immunized with seven intramuscular injections of gp130-KLH, equivalent to a total of about 1.1 mg of purified gp130 per animal.