Production of Long-Lived Neutralizing Antibodies to HIV-1 IIIB in Mice with a Vaccinia Recombinant Virus-Infected Cell Vaccine Expressing gp160

Parry, Catherine; McLain, Lesley; Dimmock, Nigel J.

doi:10.1089/aid.1994.10.205

Cited by 6 publications

(2 citation statements)

References 25 publications

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“…There have been several studies that have shown the generation of anti-gp160 immune responses in mice that had been vaccinated with recombinant vaccinia expressing the HIV-1 envelope protein (10,55,56). These studies utilized a variety of immunization protocols, some of which included boosting with recombinant protein.…”

Section: Cloned T Cell Cytolytic and Proliferation Assays Of Mhc II Pmentioning

confidence: 99%

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The Enhanced Immune Response to the HIV gp160/LAMP Chimeric Gene Product Targeted to the Lysosome Membrane Protein Trafficking Pathway

Ruff

Guarnieri

Staveley-O’Carroll

et al. 1997

Journal of Biological Chemistry

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The lysosome-associated membrane proteins (LAMP), found in the outer membrane of lysosomes and also in a multilaminar compartment that contains major histocompatibility complex class II (MHC II) proteins, are directed to their localization by a cytoplasmic carboxylterminal sequence. Our studies of the immune response to LAMP-targeted proteins has led to the application of a HIV-1 gp160/LAMP chimeric gene as a novel means to enhance the MHC II presentation of gp160. Immunofluorescence microscopy confirmed that the gp160/LAMP protein had a cellular localization corresponding to that of lysosomes. Pulse-chase analysis confirmed that the rates of synthesis of gp160/LAMP and wild type gp160 were comparable and that both proteins were processed to gp120 at similar rates. However, the gp160/LAMP was degraded more rapidly than the wild type gp160. MHC II-mediated T cell proliferation assays performed with cloned human cell lines showed that gp160/LAMP stimulated greater responses than did the wild type gp160. Moreover, mice vaccinated with recombinant vaccinia expressing gp160/LAMP had greater gp160-specific lymphoproliferation responses and higher titers of anti-V3 loop antibodies than mice vaccinated with recombinant vaccinia expressing wild type gp160.Much of the effort in developing an effective vaccine for HIV-1 has focused on the envelope protein. In addition to protein vaccines, some vaccine strategies have featured recombinant viruses that express the envelope protein (1-11), and other more recent studies have employed DNA immunization (12-17). Envelope-specific humoral and cell-mediated responses have been demonstrated by use of these approaches. However, one problem with DNA vaccines in general is that the vaccine antigen made in cells taking up the vector may not enter the major histocompatibility complex class II (MHC II) 1 antigen processing and presentation pathway, which conventionally operates only in professional antigen presenting cells (APC) that express MHC II molecules. This pathway is believed to be accessed primarily by the endocytosis or phagocytosis of extracellular proteins, with transport of the protein to endosomal/lysosomal compartments where it is proteolytically degraded, and the antigenic peptides loaded onto MHC II molecules for transport to the cell surface and presentation to CD4 ϩ T cells (18 -20). Some endogenously synthesized membrane proteins, including the influenza hemagglutinin and HIV envelope protein, are also presented by MHC II molecules, presumably by endocytosis from the cell surface or other suggested pathways (21-24).We have hypothesized that the targeting of recombinant antigens to the lysosome-associated membrane protein (LAMP) trafficking pathway will enhance the loading of endogenously synthesized antigen onto MHC II molecules and consequently elicit an enhanced CD4 ϩ helper T cell response with the resulting increase in both humoral and cell-mediated immunity. The basis of this approach is to create a chimeric antigen containing the endosomal/lysosomal localization ...

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Section: Cloned T Cell Cytolytic and Proliferation Assays Of Mhc II Pmentioning

confidence: 99%

“…In addition to protein vaccines, some vaccine strategies have featured recombinant viruses that express the envelope protein (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), and other more recent studies have employed DNA immunization (12)(13)(14)(15)(16)(17). Envelope-specific humoral and cell-mediated responses have been demonstrated by use of these approaches.…”

mentioning

confidence: 99%

The Enhanced Immune Response to the HIV gp160/LAMP Chimeric Gene Product Targeted to the Lysosome Membrane Protein Trafficking Pathway

Ruff

Guarnieri

Staveley-O’Carroll

et al. 1997

Journal of Biological Chemistry

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Characterization of a Novel Human Immunodeficiency Virus Type 1 Neutralizable Epitope within the Immunodominant Region of gp41

et al. 2000

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Previously, we generated human monoclonal antibodies using peripheral blood mononuclear cells from an asymptomatic human immunodeficiency virus type 1 (HIV-1)-seropositive donor. One of these monoclonal antibodies (designated clone 3, CL3) recognized 10 amino acids (GCSGKLICTT) within the immunodominant region (cluster I) of the transmembrane envelope glycoprotein gp41 and neutralized infection of target cells with different laboratory isolates. Because the epitope recognized by CL3 has two cysteine residues that could potentially produce a disulfide loop in gp41, we analyzed binding of our monoclonal antibody to the cyclic and linear motif of the peptide sequence IWGCSGKLICTTAVP (residues 600-614). The CL3 antibody did not bind to the synthetic cyclic peptide but did recognize the linear form. Two polyclonal rabbit sera against both the linear and cyclic peptides were then generated. Both antisera bound to viral glycoproteins gp41 and gp160, but neither sera neutralized HIV-1 laboratory isolates. Using a set of alanine-substituted IWGCSGKLICTTAV peptides, we analyzed binding of polyclonal antisera and CL3. The profile of binding of polyclonal antisera to these peptides was different from that of CL3 to the same peptides. This suggests that CL3 recognized a unique neutralizable core epitope, which was not immunogenic in either the cyclic or the linear IWGCSGKLICTTAVP peptides used as immunogens in the rabbits.

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Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus

McLain

Durrani

Wisniewski³

et al. 1996

Vaccine

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Production of Long-Lived Neutralizing Antibodies to HIV-1 IIIB in Mice with a Vaccinia Recombinant Virus-Infected Cell Vaccine Expressing gp160

Cited by 6 publications

References 25 publications

The Enhanced Immune Response to the HIV gp160/LAMP Chimeric Gene Product Targeted to the Lysosome Membrane Protein Trafficking Pathway

The Enhanced Immune Response to the HIV gp160/LAMP Chimeric Gene Product Targeted to the Lysosome Membrane Protein Trafficking Pathway

Characterization of a Novel Human Immunodeficiency Virus Type 1 Neutralizable Epitope within the Immunodominant Region of gp41

Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus

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