Temporal development of cross-neutralization between HTLV-III B and HTLV-III RF in experimentally infected chimpanzees

Sera from chimpanzees inoculated respectively with HTLV-III B, LAV, HTLV-III RF and brain tissue from an AIDS patient were analysed for neutralizing activity by two methods: a cell fusion inhibition test (CFI) using HTLV-III B infected cells as inoculum and CD4+ cells as target and a replication inhibition test (RIT) using cell-free HTLV-III B as well as HTLV-III RF as inoculum and also CD4+ cells as target. All chimpanzees seroconverted for HTLV-III B antibodies within 2 months after inoculation and the ten sera included in the study recognized the HTLV-III B core proteins p17 and p24 and the transmembrane protein gp41 by immunoblotting. The HTLV-III B external envelope gp120 was recognized by eight sera with antibodies active in the CFI (CFI-Ab) or in the RIT (VN-Ab) using HTLV-III B as inoculum, while neither of two sera without such reactivity did. HTLV-III B CFI-Ab and HTLV-III B VN-Ab concurred in nine of ten serum samples. LAV and HTLV-III B infection induced HTLV-III B CFI-Ab and HTLV-III B VN-Ab within 9 months after inoculation in all four chimpanzees tested. However, only the serum of one of the four animals also neutralized HTLV-III RF. HTLV-III RF inoculation evoked only HTLV-III RF VN-Ab within nine months. Between 11 and 18 months neutralizing activity to both HTLV-III B and HTLV-III RF was found in all four sera of chimpanzees inoculated with HTLV-III B, LAV or HTLV-III RF.(ABSTRACT TRUNCATED AT 250 WORDS

Vaccination antirabique de renardeaux à l’aide d’un vaccin inactivé

Pastoret Paul-Pierre, Schwers A., Thiriart C., Iokem A., Costy F., Brochier Bernard. Vaccination antirabique de renardeaux à l’aide d’un vaccin inactivé. In: Revue d'Écologie (La Terre et La Vie), tome 40, n°2, 1985. pp. 267-268

Effects of natural sequence variation on recognition by monoclonal antibodies neutralize simian immunodeficiency virus infectivity.

The determinants of immune recognition by five monoclonal antibodies (KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus infectivity were analyzed. These five neutralizing monoclonal antibodies were generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus recombinant vector. All five recognize conformational or discontinuous epitopes and require native antigen for optimal recognition. These monoclonal antibodies also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural variants of SIVmac239, 1-12 and 8-22, which evolved during the course of persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which were constructed by exchanging variable regions between SIVmac239 and variant 1-12 were used to define domains important for recognition. Radioimmunoprecipitation analysis demonstrated that sequence changes in variable regions 4 and 5 (V4/V5) were primarily responsible for the loss of recognition of the 1-12 variant. Site-specific mutants were used to define precise changes that eliminate recognition by these neutralizing antibodies. Changing N-409 to D, deletion of KPKE, and deletion of KEQH in V4 each resulted in loss of recognition by all five monoclonal antibodies. SIVs with these natural sequence changes are still replication competent and viable. Changing A-417 to T or A/N-417/418 to TK in V4 or Q-477 to K in V5 did not alter recognition detectably. These results define specific, naturally occurring sequence changes in V4 of SIVmac that result in loss of recognition by one class of SIVmac neutralizing antibodies

Theoretical and functional analysis of the SIV fusion peptide.

The fusion domain of simian immunodeficiency virus (SIV) envelope glycoproteins is a hydrophobic region located at the amino-terminal extremity of the transmembrane protein (gp32). Assuming an alpha helical structure for the SIV fusogenic domain of gp32 in a lipid environment, theoretical studies have predicted that the fusion peptide would insert obliquely in the lipid bilayer. This oblique insertion could be an initial step of the fusion process by disorganizing locally the structure of the lipid bilayer. We have tested this hypothesis by selectively mutagenizing the SIV gp160 expressed via a vaccinia virus vector, to alter the theoretical angle of insertion of the fusion peptide. The fusogenic activity of the wild-type and mutant glycoproteins was tested after infection of T4 lymphocytic cell lines by the recombinant vaccinia virus, and measure of syncytia formation. Mutations that modified the oblique orientation reduced the fusogenic activity. In contrast, mutations that conserve the oblique orientation did not alter the fusogenic properties. Our results support the hypothesis that oblique orientation is important for fusogenic activity

The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells.

The induction of immune responses in vivo is typically performed with antigens administered in external adjuvants, like alum, complete Freund's adjuvant, LPS and, more recently, monophosphoryl lipid A (MPL). However, the role of the adjuvant is still poorly defined. The aim of this study was to test whether the MPL affects the function of antigen-presenting cells (APC) in vitro and in vivo. Antigen-pulsed APC [including macrophages, B cells and dendritic cells (DC)] were incubated or not with MPL, and their ability to sensitize naive T cells was tested in vitro and in vivo. The data show that MPL enhances the ability of macrophages and B cells to sensitize naive T cells, and confers to them the capacity to induce the development of T(h)1 and T(h)2. Administration of MPL i.v. in mice results in the redistribution of fully mature DC in the T cell area of the spleen. These observations suggest that MPL may induce an antigen-specific primary immune response by provoking the migration and maturation of DC that are the physiological adjuvant of the immune system.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

An HIV-1 and HIV-2 cross-reactive cytotoxic T-cell epitope.

The HLA-B27-restricted HIV gag cytotoxic T-lymphocyte (CTL) epitope, 265-279, is highly conserved amongst HIV-1 isolates, only one, HIV-1ELI, having a single amino acid substitution. Over the same region HIV-2 differs by five amino acids. As a broadly cross-protective AIDS vaccine should protect against infection from all isolates of HIV-1 and HIV-2, we tested CTL specific for the HIV-1 265-279 epitope with peptide analogues from HIV-1ELI, HIV-2 and two simian immunodeficiency virus (SIV) isolates, and with recombinant vaccinia viruses expressing the respective gag genes, to determine whether there was any cross-reactivity for this CTL epitope. CTL from the HIV-1-infected donor could recognize the HIV-1ELI peptide, the HIV-2 peptide and recombinant vaccinia virus-infected target and one of the two SIV peptide-treated targets. Epitopes that exhibit such cross-reactivity may be valuable in vaccine design

Virus load in chimpanzees infected with human immunodeficiency virus type 1: effect of pre-exposure vaccination

Many reports indicate that a long-term asymptomatic state following human immunodeficiency virus type 1 (HIV-1) infection is associated with a low amount of circulating virus. To evaluate the possible effect of stabilizing a low virus load by non-sterilizing pre-exposure vaccination, a quantitative virus isolation method was developed and evaluated in four chronically infected chimpanzees infected with a variety of HIV-1 related isolates. This assay was then used to monitor a group of chimpanzees (n = 6) challenged with HIV-1 following vaccination with gp120 or gp160. Data indicated that of the three vaccinated animals which became infected after challenge, the animal with the lowest neutralizing titre at the time of challenge acquired a virus load similar to the control animals, whereas the two other chimpanzees had reduced numbers of virus producing cells in their peripheral circulation. One animal became virus isolation negative, developed an indeterminant PCR signal on lymph node DNA and subsequently became negative for HIV-1 DNA as determined by PCR on PBMC (peripheral blood mononuclear cells) and bone marrow DNA. Recently, the second animal has also become PCR negative. To confirm observations from quantitative virus isolations, quantification of HIV-1 DNA in PBMC and virus RNA in serum was performed by PCR on serially diluted samples at two different time points. Comparison of virus load as determined by these three methods confirmed that there was an effect of vaccination in reducing virus load and demonstrated a correlation between decreased numbers of virus producing cells, HIV-1 DNA containing cells and virus RNA molecules in seru