RESUMO
BACKGROUND: Long-term treatment with a high-strength hydroquinone (HQ) cream (usually 4% HQ) is the mainstay therapy for hyperpigmentation disorders. Instability and high potential for irritancy hinders patient compliance. A new 4% HQ preparation has been designed with an innovative antioxidant for stability and a biomimetic of an herbal extract for skin calming. AIMS: To investigate the activity, stability, and irritancy of a new HQ cream. METHODS: To evaluate the new HQ cream in comparison with commercial 4% HQ creams for stability by temperature stress test, for irritancy by repeated-insult patch test on human subjects, and for lightening effect using the MelanoDerm B skin equivalent model. RESULTS: The new HQ is more resistant to browning and shows less irritancy than three commercially available 4% HQ products. It has comparable bleaching effect with faster onset than a 4% HQ product containing 0.05% tretinoin and 0.01% fluocinolone acetonide. CONCLUSION: Based on its improved stability, lower irritancy, and activity in skin lightening, the new approach to the formulation of 4% HQ may improve therapeutic outcomes by improving patient compliance to dosing.
Assuntos
Dermatite Irritante/etiologia , Fármacos Dermatológicos/administração & dosagem , Hidroquinonas/administração & dosagem , Hiperpigmentação/tratamento farmacológico , Melanócitos/efeitos dos fármacos , Adulto , Alcaloides/administração & dosagem , Antioxidantes/administração & dosagem , Células Cultivadas , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/química , Combinação de Medicamentos , Estabilidade de Medicamentos , Ergotioneína/administração & dosagem , Feminino , Humanos , Hidroquinonas/efeitos adversos , Hidroquinonas/química , Masculino , Melaninas/biossíntese , Melanócitos/metabolismo , Quinazolinas/administração & dosagem , Testes de Irritação da Pele , Estatísticas não ParamétricasRESUMO
The UBITh AD immunotherapeutic vaccine for Alzheimer's disease uses an amyloid-beta (Abeta) immunogen having two designer peptides that have been engineered to elicit anti-N terminal Abeta(1-14) antibodies while minimizing potential for the generation of adverse anti-Abeta immune responses. The vaccine has been further designed for minimization of inflammatory reactivities through the use of a proprietary vaccine delivery system that biases Th2 type regulatory T cell responses in preference to Th1 pro-inflammatory T cell responses. In vitro studies and in vivo studies in small animals, baboons and macaques show that anti-Abeta antibodies are generated with the expected N-terminus site-specificity, and that these antibodies have functional immunogenicities to neutralize the toxic activity of Abeta and promote clearance of plaque deposition. The antibodies appear to draw Abeta from the CNS into peripheral circulation. Results indicate that the UBITh AD vaccine did not evoke anti-Abeta cellular responses in a transgenic mouse model for AD. The vaccine was safe and well tolerated in adult Cynomolgus macaques during a repeat dose acute and chronic toxicity study.
Assuntos
Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/administração & dosagem , Especificidade de Anticorpos , Fragmentos de Peptídeos/administração & dosagem , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/imunologia , Animais , Formação de Anticorpos , Encéfalo/patologia , Modelos Animais de Doenças , Desenho de Fármacos , Ensaio de Imunoadsorção Enzimática , Cobaias , Imunoterapia , Macaca , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Vacinas/administração & dosagemRESUMO
United Biomedical, Inc. (UBI) has developed a set of core technologies for the discovery and production of synthetic peptide-based immunotherapeutics and vaccines. These core technologies have led to products that stimulate functional site-directed antibody responses for therapeutic effects. UBI active immunotherapies can be used to modulate physiological processes effective for the control of cell entry by HIV virions, for control of prostate cancer and allergy, and for immunocastration in livestock leading to boar taint elimination and growth promotion in swine. The UBI technologies are also useful to stimulate site-directed antibodies against pathogenic agents such as foot-and-mouth disease virus. UBITh Immunotherapeutic peptides were developed as antigens to direct antibody responses against targeted epitopes on self-proteins and viral pathogens that are responsible for biological functions and pathogenicity. A collection of promiscuous UBITh T helper cell epitopes was used to impart these functionally antigenic peptides with immunogenicity. The T cell helper epitopes were covalently linked to the functional antigenic target sites by peptide synthesis, creating well-defined synthetic immunogens. Finally, vaccine formulations were selected appropriate for the delivery of peptide immunogens. Controlled production processes and the means to characterize the final product provide a framework for the GMP-compliant manufacture of UBITh immunotherapeutics and vaccines.
Assuntos
Vacinas de Subunidades Antigênicas/isolamento & purificação , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/isolamento & purificação , Sequência de Aminoácidos , Animais , Anticorpos Anti-Idiotípicos/biossíntese , Vacinas Anticâncer/isolamento & purificação , Cães , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Humanos , Hipersensibilidade/terapia , Imunização , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Imunoterapia/métodos , Imunoterapia/veterinária , Masculino , Dados de Sequência Molecular , Orquiectomia/métodos , Orquiectomia/veterinária , Neoplasias da Próstata/terapia , Ratos , Sus scrofa , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. The assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-associated coronavirus. The new peptide ELISA consistently detected seroconversion by week 2 of onset of fever, and seropositivity remained through day 100. Specificity was 100% on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. The peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for SARS. The assay was used for a retrospective survey of healthy healthcare workers in Taiwan who treated SARS patients. Asymptomatic seroconversions were detected in two hospitals that had nosocomial disease.
Assuntos
Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Surtos de Doenças , Humanos , Vigilância da População/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologiaRESUMO
We have designed a peptide-based immunotherapeutic vaccine for treatment of androgen-responsive prostate cancer. The vaccine targets the luteinizing hormone-releasing hormone (LHRH) decapeptide that results in an androgen-deprivation immunotherapy. The design elements of the peptide immunogens are the LHRH peptide or B cell epitope synthetically linked to different promiscuous helper T cell (Th) sequences, the UBITh epitopes, derived from four natural pathogens for effective immunogenicity in outbred populations, and in some cases, also linked to an adjuvanting peptide from Yersinia invasin (Inv) protein. The UBITh LHRH immunogens are adsorbed on Alhydrogel or formulated as several different oil-based emulsions and tested in rodents, dogs, and a non-human primate, baboons. The immunogens generate an anti-LHRH antibody response specific to the LHRH decapeptide element in contrast to LHRH conjugate-carrier protein vaccines where only a small portion of the antibody response is directed to the target epitope and epitopic suppression is noted. Individual UBITh peptide domains, but not the LHRH and Inv peptide domains, are stimulatory in lymphocyte cultures. The UBITh LHRH immunogens in a clinically applicable formulation, controlled the growth of Dunning R3327-H androgen-responsive prostate tumor cells in rats. The results demonstrate universal responsiveness and long duration of androgen deprivation from three diverse species, and thus vaccine efficacy.
Assuntos
Androgênios/metabolismo , Hormônio Liberador de Gonadotropina/imunologia , Neoplasias da Próstata/terapia , Vacinas/imunologia , Animais , Cães , Desenho de Fármacos , Ensaio de Imunoadsorção Enzimática , Hormônio Liberador de Gonadotropina/sangue , Humanos , Imunoterapia , Masculino , Transplante de Neoplasias , Papio , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/prevenção & controle , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Testosterona/sangue , Vacinas/síntese química , Vacinas de Subunidades Antigênicas/síntese química , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
An immunotherapeutic vaccine for allergy was produced by designing IgE-based synthetic peptide immunogens and selecting them for functional immunogenicity. The vaccine targets the binding site on IgE for the high affinity receptor Fc epsilon RI, by active immunization. The peptide target site on IgE heavy chain was selected from among the amino acid sequences for the C epsilon 2, C epsilon 3, and C epsilon 4 domains. These were characterised by epitope mapping studies for cross-reactivity to IgE and functional antigenicity. A peptide, modified from positions 413-435 of a loop region of C epsilon 3 and subjected to conformational constraint, elicited anti-IgE antibodies that blocked IgE-mediated histamine release. It was immunopotentiated by linkage to a promiscuous T helper site to produce a wholly synthetic chimaeric immunogen. This immunogen was shown to induce polyclonal site-specific anti-IgE antibodies that obstruct binding to Fc epsilon RI, inhibit histamine release by IgE-sensitised basophils, inhibit passive cutaneous anaphylaxis, and do not signal degranulation. Immunized dogs experienced significant reductions in total serum IgE.
Assuntos
Dessensibilização Imunológica/métodos , Hipersensibilidade/prevenção & controle , Imunoglobulina E/uso terapêutico , Sequência de Aminoácidos , Animais , Sítios de Ligação de Anticorpos , Cães , Sistemas de Liberação de Medicamentos/métodos , Cobaias , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Receptores de IgE/metabolismo , Suínos , Vacinas de Subunidades Antigênicas/uso terapêutico , Vacinas Sintéticas/uso terapêuticoRESUMO
A class of synthetic peptide immunogens for the cell surface HIV receptor complex has been developed to elicit antibodies that block viral entry by inhibiting gp120-CD4 interaction. These peptides extend our HIV receptor-directed approach from passive immunotherapy with mAb B4 (Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 10367) to active immunization by a synthetic peptide-based vaccine. A peptide site from CD4 was identified as a B cell epitope capable of mimicking a susceptible site on the HIV receptor complex, and then rendered immunogenic. An effective target antigenic site (B cell epitope) for the cell surface HIV receptor complex was selected by epitope mapping from among diverse CD4 and chemokine receptor peptides. It is a cyclized sequence modified from the CDR2-like domain of CD4 (AA 39-66), that was predicted to produce steric hindrance of the discontinuous recognition site of mAb B4. The immunogenicity of the targeted epitope was augmented by tandem combination with promiscuous T helper cell epitopes (Th). The antibody response to this class of immunogens attained sufficient concentrations and affinities of the correct specificity to block the interactions of HIV env glycoprotein with the cellular receptor, and prevent infection. The polyclonal antibodies generated against these fusion constructs in multiple animal species neutralized a broad array of HIV-1 primary isolates from clades A to E. Despite eliciting antibodies to the key CD4 immunomodulatory molecule, the site-specific and chemically defined immunogens displayed no overt immunotoxicity in baboons and have potential for the immunotherapy and immunoprophylaxis of HIV infection.
Assuntos
Vacinas contra a AIDS/imunologia , Antígenos CD4/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Vacinas Sintéticas/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/síntese química , Vacinas contra a AIDS/química , Animais , Epitopos/análise , Cobaias , HIV-1/isolamento & purificação , Humanos , Técnicas In Vitro , Testes de Neutralização , Suínos , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/isolamento & purificaçãoRESUMO
We have designed a peptide-based vaccine for foot-and-mouth disease (FMD) effective in swine. The peptide immunogen has a G-H loop domain from the VP1 capsid protein of foot-and-mouth disease virus (FMDV) and a novel promiscuous T helper (Th) site for broad immunogenicity in multiple species. The G-H loop VP1 site was optimised for cross-reactivity to FMDV by the inclusion into the peptide of cyclic constraint and adjoining sequences. The incorporation of consensus residues into the hypervariable positions of the VP1 site provided for broad immunogenicity. The vaccine protected 20 out of 21 immunised pigs from infectious challenge by FMDV O1 Taiwan using peptide doses as low as 12.5 microg, and a mild adjuvant that caused no lesions. A safe chemically-defined product would have considerable advantages for vaccination against FMD.