Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the established T-cell lines. Each isolate is closely related to the first HTLV isolate, and all the new HTLV isolates were transmitted into normal human T cells obtained from the umbilical cord blood of newborns.

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Whereas several recent AIDS vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (SHIV) 89.6P challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic SIV, which is more representative of HIV infection of people. We show here that priming with replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes, followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4 binding region of the envelope, protects rhesus macaques from intrarectal infection with the highly pathogenic SIV mac251 . Using trend analysis, significant reductions in acute-phase and set point viremia were correlated with anti-gp120 antibody and cellular immune responses, respectively. Within immunization groups exhibiting significant protection, a subset (39%) of macaques have exhibited either no viremia, cleared viremia, or controlled viremia at the threshold of detection, now more than 40 weeks postchallenge. This combination prime-boost strategy, utilizing replication competent adenovirus, is a promising alternative for HIV vaccine development.

Type-C RNA tumor viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T-cell leukemia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T-cells in tissue culture usually with T-cell growth factor (TCGF). We now report a cluster of adult T-cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HTLV virus and/or antibody. These patients have disease that appears indistinguishable from Japanese adult T-cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90% of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T-cell leukemia/lymphoma in these virus-endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico-pathologic entity.

The identification of HIV envelope structures that generate broadly cross-reactive neutralizing antibodies is a major goal for HIVvaccine development. In this study, we evaluated one such structure, expressed as either a gp120 -CD4 or a gp140 -CD4 complex, for its ability to elicit a neutralizing antibody response. In rhesus macaques, covalently crosslinked complexes of soluble human CD4 (shCD4) and HIV-1 IIIB envelope glycoproteins (gp120 or gp140) generated antibodies that neutralized a wide range of primary HIV-1 isolates regardless of the coreceptor usage or genetic subtype. Ig with cross-reactive neutralizing activity was recovered by affinity chromatography with a chimeric single-chain polypeptide containing sequences for HIV BaL gp120 and a mimetic peptide that induces a CD4-triggered envelope structure. These results suggest that covalently crosslinked complexes of the HIV-1 surface envelope glycoprotein and CD4 elicit broadly neutralizing humoral responses that, in part, may be directed against a novel epitope(s) found on the HIV-1 envelope.gp120 ͉ gp140 ͉ gp120 -CD4 complex ͉ vaccine A safe and effective vaccine against HIV should elicit humoral responses that are effective against a broad spectrum of primary HIV strains (1). Unfortunately, an immunogen capable of generating such antibodies in humans remains elusive. The structural and antigenic characteristics of the free HIV envelope (Env) have been studied intensively in hopes of identifying a configuration that might serve as a subunit immunogen. However, these efforts have produced Env-based immunogens that typically fail to elicit antibodies capable of neutralizing more than a minor fraction of primary isolates (2-9).The gp120-CD4 complex, which forms during virus attachment to cell surface receptor CD4 (10), has been considered as another potential target for broadly neutralizing antibodies. This complex is antigenically distinct from free gp120 and is essential for viral entry via 7-transmembrane domain (7-TM) chemokine receptors (10). Only a few studies have attempted to characterize immune sera raised by gp120-CD4 complexes for broadly cross-reactive neutralizing antibodies (11)(12)(13)(14). These studies showed that broadly neutralizing antibody responses were generated in mice by immunization with mixtures of gp120 and CD4. However, these responses were directed, in part, against the interactive domains of CD4 and gp120 and were not qualitatively different from what are elicited by the uncomplexed antigens (11, 13). In contrast, a gp120-CD4 complex, stabilized by covalent crosslinking, elicited antibody responses in goats that neutralized primary HIV isolates (12). Such an antigen can be useful for characterizing the immunogenic characteristics of HIV Env-CD4 complexes. Accordingly, in this study we evaluated the immunogenicity of crosslinked gp120-CD4 complexes in rhesus macaques, a nonhuman primate commonly used as an animal model for developing strategies to elicit protective anti-HIV immune responses. Expression and Production of HIV En...