To define protein folding patterns of HIV-1 Env subunit vaccines, we have isolated a set 30 monoclonal antibodies (MAbs) from BALB/c mice immunized with recombinant gp160 vaccine (rgp160) expressed in baculovirus system. This article describes epitope mapping for the MAb panel and topology epitopes rgp160 gp120 (rgp120) also The following results are reported: (1) harbors minimum 4 antigenic domains, 3 to C1, C2, C3/V4 regions 1 cytoplasmic tail gp41; (2) there at least adjacent or...

A murine T lymphocyte proliferation assay that used antigen-primed lymph node cells, was antigen specific, and required exogenous accessory cells to characterize the supported proliferation. These were Thy 1.2 negative, radioresistant, glass-adherent, functional only if alive. The cell function of spleen adherent much greater than peritoneal cells. Also, proportional length time such incubated with very small numbers provided function. Cytotoxic studies subregion-restricted anti-Ia...

Abstract One hundred five patients were enrolled in a 12‐week, randomized, prospective, double‐blind, placebo‐controlled trial of recombinant human γ‐interferon (rHuγ‐IFN) for the treatment rheumatoid arthritis. Fifty‐four received rHuγ‐IFN and 51 placebo. Forty‐two each group completed 12‐week trial. Some clinical improvement occurred both groups patients. Although with was greater than that placebo, differences generally not statistically significant.

Abstract A/B toxins, produced by bacteria and plants, are among the deadliest molecules known. The B chain binds cell, whereas A exerts toxic effect. Both anti-A anti-B Abs can neutralize toxins in vivo vitro. block binding of toxin to cell. It is not known how function. Working with ricin toxin, we demonstrate that immunization induces greater protection than chain. panel mAbs, chain, or both chains, has been characterized. Immunologic characteristics evaluated include isotype, relative...

mAb 907 is directed against the envelope protein of HIV. The epitope recognized by this antibody expressed in moderate density on surface tissue culture cells infected with LAV/HTLV-IIIB strain We have coupled to ricin A chain (RAC). antibody-RAC conjugate inhibited synthesis and cell growth HIV-infected cells. An irrelevant conjugated RAC had no effect. Most important, treatment markedly production infectious virus, as measured viral foci susceptible monolayer Exposure target for short a...

Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure the most likely route of contact to ricin toxin will result in severe toxicity. Early recognition essential if specific antidotes are applied. Initial diagnosis syndromic, i.e., fitting clinical laboratory signs into pattern which then guide choice more diagnostic assays therapeutic interventions. We have studied pathology rhesus macaques exposed lethal sublethal aerosols. Animals...

Microbial polysaccharides are notably poor immunogens. We have developed an alternate route for the production of Abs to important carbohydrate epitopes. mAb S9, a protective against type III capsular polysaccharide group B streptococci (GBS), was used select epitope analogues from peptide display phage library. Depending upon desorption conditions, two populations were identified with displayed sequences WENWMMGNA and FDTGAFDPDWPA. ELISA results demonstrated that these bound S9 no other...

To investigate the effectiveness of passive antibody treatment as post-exposure therapy for ricin, we had developed an oropharyngeal aspiration model ricin lethal challenge and administration. When polyclonal anti-deglycosylated A-chain (dgA Ab) was administered between 1–18 hr after challenge, all animals survived while delayed to 24 resulted in 30% survival. The protective effects dgA Ab correlated with inhibition apoptosis lungs vivo RAW264.7 macrophage Jurkat T cells vitro. In addition,...

Magnetite nanoparticle coated silica (Fe3O4@SiO2) hybrid nanomaterials hold an important position in the fields of cell imaging and drug delivery. Here we report a large scale synthetic procedure that allows attachment magnetite nanoparticles onto surface situ. Many different such as Stöber nanospheres, mesoporous nanoparticles, hollow nanotubes have been with high density layer water-dispersible nanoparticles. The size efficiency can be well tuned by adjusting precursor concentration reflux...

Abstract Immunotoxins (ITs) targeting the HIV envelope protein are among most efficacious antiviral therapies when tested in vitro. Yet a first-generation IT targeted to gp120, CD4-PE40 (chimeric immunotoxin using CD4 and translocation enzymatic domains of Pseudomonas exotoxin A), showed limited promise initial clinical testing, highlighting need for improved ITs. We have used new mouse model infection test comparative efficacy anti-HIV ITs gp120 or gp41. Irradiated SCID/nonobese diabetic...

Studies of the immune response to human immunodeficiency virus (HIV) have been hampered by antigenic diversity HIV envelope protein. In an effort predict efficacy vaccination we compared systemic anti-envelope antibody in seronegative volunteers immunized with recombinant gp160 (either vaccinia or as soluble protein produced baculovirus) derived from HTLV-IIIB strain HIV-1 and two laboratory workers accidentally infected same strain. 11 14 vaccinees responded immunization producing...

Murine monoclonal antibodies to group-B Streptococcus type III were developed by fusion of splenic lymphocytes from immunized BALB/c mice with the mouse-myeloma cell line SP 2/0. The four III-specific antibodies, which IgM class, protected neonatal rats against intraperitoneal infection homologous-type streptococci; survival rates 95%–100% for but only 17% unprotected rats. One antibody preparation offered excellent protection any five type-III strains employed. Monoclonal provided when...

We have produced and characterized six mAb directed against group B streptococci (GBS). All antibodies are IgM. previously shown that some of these highly protective in the treatment experimental infections neonatal rats, whereas others do not appear to any efficacy. Using an ELISA, we demonstrate specificity both nonprotective antibodies. Two antibodies, binding different epitopes, antigenic structures present on all GBS; two specific for type III carbohydrate determinants; one binds a...

Background Mechanisms of antibody-mediated neutralization are much interest. For plant and bacterial A-B toxins, A chain mediates toxicity B binds target cells. It is generally accepted taught that antibody (Ab) neutralizes by preventing toxin binding to Yet for some ricin included, anti-A Abs afford greater protection than anti-B. The mechanism(s) whereby the neutralize toxins not understood. Methodology/Principal Findings We use quantitative confocal imaging, assays, other techniques study...

Protein–protein interactions (PPI) play a crucial role in many biological processes and modulation of PPI using small molecules to target hot spots has therapeutic value. As model system we will use human epidermal growth factor receptors (EGFRs). Among the four EGFRs, EGFR–HER2 HER2–HER3 are well known cancer. We have designed molecule that is targeted modulate HER2-mediated signaling. Our approach novel because disrupts dimerization not only EGFR–HER2, but also HER2–HER3. In present study...

Six different anti-HIV envelope antibodies and one irrelevant control antibody were coupled to ricin A chain tested for their efficacy in inhibiting HIV tissue culture infections. The consisted of five monoclonals, three murine two human origin, polyclonal preparation prepared by affinity purifying pooled serum from HIV-infected humans on rgp160. binding specificity the was defined ELISA using recombinant proteins synthetic peptides, flow cytometry cells. vitro abilities immunotoxins inhibit...

Three laboratory workers have been infected with the IIIB strain of HIV; their antibody response to HIV has studied in serial serum specimens. Because infecting virus is known, fine specificity was on homologous HIV. Anti-p17, anti-p24, anti-gp160, CD4/gp120 blocking and neutralizing antibodies developed parallel. Epitope mapping anti-gp160 indicated several regions that consistently induced an response. Serum contained which reacted V3-specific peptides corresponding very tip loop...

ABSTRACT The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on surface both virions and infected cells. Env target neutralizing antibodies (Abs) has been subject intense study in efforts to produce vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such immunotoxins (ITs). In course screening monoclonal (MAbs) for their ability deliver agents Env-transfected cells, we noted...

Monoclonal antibodies specific for the gp120 or gp41 portions of human immunodeficiency virus (HIV) envelope protein gp160 were conjugated to ricin A chain, and their immunotoxic activities against HIV-infected cells evaluated in presence absence soluble CD4 (sCD4). Immunotoxin activity was measured vitro as cytotoxicity inhibition secretion infectious HIV. The efficacy anti-gp41 immunotoxins enhanced at least 30-fold sCD4. This effect cells, but not uninfected seen concentrations sCD4 low...