Hypervariable epitope constructs as a means of accounting for epitope variability

Anderson, David E.; Malley, Arthur; Benjamini, E.; Gardner, Murray B.; Torres, José V.

doi:10.1016/0264-410x(94)90225-9

Cited by 26 publications

(15 citation statements)

References 20 publications

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“…Peptides were prepared as described elsewhere [12]. The synthetic peptides representative of various strains of HIV-1 envelope glycoprotein (gp120) consisted of amino acids (aa) RF3V3 (aa, 313-340), SF2V2 (aa,159-194), LAI (aa, 421-443), HIV-1 subtype A V3 (aa, 266-280), and MNV5 (aa, 454-476).…”

Section: Methodsmentioning

confidence: 99%

Effect of Human Immunodeficiency Virus Type 1 on Intracellular Activation and Superoxide Production by Neutrophils

et al. 1999

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The immunopathogenesis of AIDS is associated with the development of opportunistic infections by intracellular pathogens that can invade and reproduce freely because of impaired cellular functions. Neutrophils from asymptomatic human immunodeficiency virus (HIV) type 1-infected persons and from symptomatic patients with AIDS were found to retain normal phagocytosis activity while producing significantly less superoxide than neutrophils from HIV-1-negative subjects, when stimulated through Fc receptors or protein kinase C. After priming with a synthetic HIV-1 envelope peptide and stimulation via the Fc receptor, the neutrophils from HIV-1-negative controls had suppressed superoxide production, reduced phosphorylation of two unidentified cellular proteins, and increased expression of a third phosphoprotein. These results suggest that HIV-1 can produce direct functional damage of neutrophils through binding of envelope components to the cell membrane.

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Section: Methodsmentioning

confidence: 99%

Effect of Human Immunodeficiency Virus Type 1 on Intracellular Activation and Superoxide Production by Neutrophils

et al. 1999

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“…Complete coupling was assessed by using the ninhydrin test to detect free amino groups (10). PAM peptide conjugates were cleaved from the resin, deprotected, and purified using standard procedures (1,16). The lipopeptide was cleaved from the resin using trifluoroacetic acid in the presence of phenol, thioanisol, and 1,2-ethanediol.…”

Section: Methodsmentioning

confidence: 99%

“…Peptides were synthesized by solid-phase F-moc chemistry with a PS3 automatic peptide synthesizer (Rainin Instrument Company, Wobum, MA). The technique and procedures developed for the synthesis of the HECs have been previously described elsewhere (1,16). Palmitic acid (Sigma Chemical Company, St. Louis, MO) was coupled to deprotected amino terminus of the resin-bound R group-protected peptides according to a modified published protocol (27).…”

Section: Methodsmentioning

confidence: 99%

“…Having established the ability of simian immunodeficiency virus (SIV) envelope hypervariable epitope constructs (HECs) to induce a broad cross-reactive humoral immune response (1,16) and CTL responses in Macaques, we attempted to improve cellular responses induced by HECs. As demonstrated before, we found that iron bead inoculation resulted in a CTL response similar to that obtained with unmodified HECs and that the beads remained at the immunization site (11).…”

Section: Introductionmentioning

confidence: 99%

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Induction of Cytotoxic and Helper T Cell Responses by Modified Simian Immunodeficiency Virus Hypervariable Epitope Constructs

Meyer¹,

Torres

1999

Viral Immunology

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We previously reported the broad humoral immunogenicity of peptides synthesized according to the cumulative variability of an epitope (1,16). These peptides, hypervariable epitope constructs (HECs), are designed to represent the envelope glycoproteins of several isolates of the simian immunodeficiency virus (SIV). When HEC peptides were conjugated to palmitic acid and palmitic acid ester (lipoHECs), they promoted the induction of cellular immune responses. SIV envelope lipoHEC immunization of BALB/c and ICR mice resulted in up to 80% cytotoxic T lymphocyte (CTL) lysis of SIV envelope-expressing target cells and SIV envelope-specific delayed type hypersensitivity (DTH). This DTH response was significantly higher than that of single peptide controls, and the response peaked at 24 hours. Strong SIV envelope-specific T-cell proliferative responses were also induced in mice with stimulation indexes higher than 20 for spleen cells and higher than 10 for lymph node cells. Overall, our results demonstrate that conjugation of these variable synthetic peptides to a lipid moiety results in an immunogen capable of inducing strong and cross-reactive cellular immune responses.

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“…The method for designing the HEC based on these regions has been described elsewhere (2,3,8,9,22,23). Our previous work demonstrated that HECs based on hypervariable regions of simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) induce broadly reactive humoral as well as T-helper cell responses in rodents and non-human primates (2,3,8,22,23).…”

Section: Introductionmentioning

confidence: 99%

Synthetic Antigens Representing the Antigenic Variation of Human Hepatitis C Virus

et al. 2010

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Immune responses against hepatitis C virus (HCV) have been studied by numerous groups. However, details concerning the production of antibodies to antigenically variable epitopes remain to be elucidated. Since the sequences of the variable regions of several HCV proteins are different among the virus strains infecting patients, we decided to design peptide combinations that represent the theoretical maximum antigenic variation of each epitope to be used as capture antigens. We prepared six peptide mixtures (hypervariable epitope constructs; HECs) representing six different epitopes from structural and non-structural proteins of HCV from genotypes 1-6. Plasma from 300 HCV patients was tested to determine if their antibodies recognize the synthetic constructs. All the patients were chronically infected with diverse HCV genotypes and did not receive antiviral treatment. Antibodies to one or more of the HECs were detected in all of the HCV-infected individuals. Immunogenicity of the HCV HECs was also evaluated in outbred and inbred mice. Strong HEC-specific antibodies were produced, and cellular responses were also induced that were Th-1 rather than Th-2. Our results show that HCV HECs are both antigens that can be used to detect the broad cross-reactivity of antibodies from HCV-infected patients, and strong immunogens that can induce antigen-specific humoral and cellular immune responses in mice.

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Hypervariable epitope constructs as a means of accounting for epitope variability

Cited by 26 publications

References 20 publications

Effect of Human Immunodeficiency Virus Type 1 on Intracellular Activation and Superoxide Production by Neutrophils

Effect of Human Immunodeficiency Virus Type 1 on Intracellular Activation and Superoxide Production by Neutrophils

Induction of Cytotoxic and Helper T Cell Responses by Modified Simian Immunodeficiency Virus Hypervariable Epitope Constructs

Synthetic Antigens Representing the Antigenic Variation of Human Hepatitis C Virus

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