Publications (6)12.7 Total impact
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Article: A human anti-HIV autoantibody enhances EBV transformation and HIV infection.
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ABSTRACT: A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. This reactivity with uninfected cells is inhibited by free gp120 demonstrating the cross-reactive nature of this antibody. The F223 light chain demonstrates strong homology to VLlambda2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HIV-1 (gp41) human mAb, 3D6, with related autoreactivity, suggests that VH3 sequences may be important components of potentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was isolated from an HIV-1 infected individual with lymphoma and in vitro F223 significantly enhances EBV transformation of normal B cells and increases immunoglobulin production without affecting B cell proliferation. Characterization of this antibody response may provide important insights and mechanistic information on HIV pathogenesis.Clinical Immunology 01/2000; 93(3):263-73. · 4.05 Impact Factor -
Article: Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120.
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ABSTRACT: A phase I dose escalation study was conducted with the human monoclonal anti-gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional activity of F105 in HIV-1-infected individuals. F105 is an IgG1(kappa) antibody reactive with a discontinuous epitope that overlaps the CD4-binding site of gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates, and synergizes with other antibodies in neutralizing an expanded spectrum of isolates. Four patients each with CD4 counts between 200 and 500/mm3 received a single dose of F105 at 100 or 500 mg/m2, intravenously. Sustained levels of F105 were obtained in plasma, and there was no evidence of an immune response to F105 as determined by a double-antigen immunoassay. No patient experienced any toxicity. Infused antibody retained full functional activity as detected by the ability of sera to block the binding of labeled F105 to HIV-1-infected cells. Of note, all patients had preexisting antibody to the gp120 CD4-binding site. The ability to culture virus by quantitative microculture remained unchanged by this single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic as a single injection at the doses tested. Furthermore, the antibody retains full gp120-binding activity. In these patients, with preexisting CD4-binding site antibody, there is no evidence of anti-HIV-1 activity following a single antibody infusion.AIDS Research and Human Retroviruses 06/1998; 14(7):545-50. · 2.25 Impact Factor -
Article: Human antibody variable region gene usage in HIV-1 infection.
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ABSTRACT: Human antibody variable region gene usage during human immunodeficiency virus type 1 (HIV-1) infection is examined in the following review, and several hypotheses are presented to account for the distinct patterns of antibody gene expression associated with infection. Evidence supporting qualitatively biased antibody gene expression has been derived from analysis of the human humoral immune response by isoelectric focusing (IEF) and serological and molecular studies of immunoglobulin (Ig) from different lymphoid compartments of HIV-1-infected patients. Preferential usage of heavy-chain variable region (VH) gene families 1 and 4 is supported by serological studies of serum Ig and molecular characterization of anti-HIV-1 human monoclonal antibodies derived from infected patients. Negative biases against VH3 family gene usage are detected by polymerase chain reaction (PCR) studies of peripheral blood lymphocytes from AIDS patients but not by combinatorial phage display library techniques. Biased antibody gene usage and expression during HIV-1 infection may be related to HIV-1 pathogenesis by limiting the available HIV-1 neutralizing repertoire. Further molecular characterization of anti-HIV-1 antibodies and in vivo expression of V-region genes during HIV-1 infection should provide important information regarding antibody gene expression and its relationship to HIV-1 pathogenesis.Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 02/1996; 11(1):31-8. -
Article: Induction of hepatic pathology in SCID-Hu mice engrafted with peripheral blood lymphocytes of patients with Schistosomiasis japonica.
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ABSTRACT: SCID mice were engrafted with peripheral blood lymphocytes (PBL) derived from persons currently or previously infected with Schistosoma japonicum. After immunization with soluble worm antigenic preparation, the SCID-Hu mice were analyzed for a human immune response. ELISA revealed a low titer of human antibody recognizing soluble egg antigens in 2 of 10 mice. One mouse had detectable levels of interleukin (IL)-2 and gamma-interferon, TH1 phenotype cytokines. All mice had elevated levels of IL-4, a TH2 phenotype cytokine. The human cytokine profile of the mice paralleled the patient's serum profile at clinical examination. In addition, all mice had substantial hepatic pathology, including inflammatory cell infiltrates and macrovesicular fat deposition. The data indicate that activation of PBL from patients with a history of schistosomiasis japonica infection can result in focal hepatic pathology, which may be driven by specific cytokines.The Journal of Infectious Diseases 10/1994; 170(3):733-6. · 6.41 Impact Factor -
Article: Human monoclonal antibodies against Cryptosporidium parvum generated by hypo-osmolar electrofusion.
Transactions of the Association of American Physicians 02/1993; 106:86-90. -
Article: An immunoregulatory human monoclonal antibody in schistosomiasis japonica.
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ABSTRACT: A series of human monoclonal antibodies were generated using splenocytes from a Chinese patient with chronic schistosomiasis who had undergone splenectomy as part of a portacaval decompression operation. Splenocytes were transformed in bulk culture by Epstein Barr virus and transformants fused with the HMMA 2.11 TG/O cell line. Twenty individual IgG antiworm and egg antibody-producing hybridomas were generated and screened for antigen reactivity by Western blot and for suppression of antigen-induced blastogenesis of murine splenocytes from Schistosoma japonicum-infected animals. Only one IgG clone significantly suppressed (56% P less than 0.05) soluble egg antigen (SEA)-induced blastogenesis. This human monoclonal antibody bound a 50 kD carbohydrate antigen on Western blot analysis, binding both the adult worm and egg antigens of this parasite. The non-regulatory monoclonal antibodies bound this same molecule present in adult worms but not the corresponding molecule in a preparation of soluble eggs. Thus, specific immunoregulatory epitopes can be identified by human monoclonal antibodies generated from patients with chronic disease.Human antibodies and hybridomas 02/1991; 2(1):42-5.
