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1.
Biotechnol Appl Biochem ; 27(2): 89-95, 1998 04.
Artigo em Inglês | MEDLINE | ID: mdl-9569603

RESUMO

The murine model was developed to assess the effects of maternally transferred HIV hyperimmune globulin or human intravenous immune globulin on the immunization of the offspring at 18-21 days of age with rgp 120SF2-complete Freund's adjuvant. Either HIV hyperimmune globulin or intravenous immune globulin was administered intraperitoneally to post-partum BALB/c mice and was transferred via milk to the offspring. Both HIV hyperimmune globulin and intravenous immune globulin inhibited the offspring anti-rgp 120SF2 IgG response to the vaccine. The HIV hyperimmune globulin inhibition persisted for 28 days after immunization while the intravenous immune globulin inhibition was still present at 63 days after immunization. In addition, the intravenous immune globulin had a more generalized immunosuppressive effect, inhibiting the IgG response to both rpg 120SF2 and an additional protein antigen, hen egg-white lysozyme. Effects of maternal or exogenously administered pre-existing antibody, including control antibodies (intravenous immune globulin), on the newborn response to HIV and other vaccines must be carefully evaluated when vaccine studies proceed in newborns.


Assuntos
Vacinas contra a AIDS/farmacologia , Anticorpos Anti-HIV/farmacologia , Imunidade Materno-Adquirida/efeitos dos fármacos , Imunoglobulinas Intravenosas/farmacologia , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Feminino , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunoglobulina G/análise , Imunoglobulina G/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular
2.
Vaccine ; 15(8): 869-73, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9234536

RESUMO

Small animals were immunized with plasmid DNA encoding HIV-1 envelope gp120 either intramuscularly by needle injection (mice and guinea pigs) or epidermally with the Accell gene gun (guinea pits). Subsequently, the animals were boosted with a recombinant gp120 protein subunit vaccine in an oil-in-water based adjuvant, MF59. Antibodies and cytotoxic T-lymphocyte (CTL) immune responses to the HIV envelope glycoprotein were observed in animals immunized with gp120 DNA derived from the HIV-1SF2 laboratory strain or from HIV-1 field isolates. Titers of ELISA antibodies and serum neutralizing antibodies against the HIV-1SF2 laboratory isolate were substantially increased in DNA-immunized animals following a single boost with recombinant gp120 protein subunit. This DNA prime/protein subunit boost immunization approach may be important for vaccination against infectious agents such as HIV for which it is difficult to raise strong antiviral humoral responses with DNA vaccination alone.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , Vacinas de DNA/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Adjuvantes Imunológicos , Animais , Biolística , DNA Viral/imunologia , Ensaio de Imunoadsorção Enzimática , Cobaias , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/genética , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/genética , Polissorbatos/análise , Esqualeno/análise , Esqualeno/imunologia , Tensoativos , Linfócitos T Citotóxicos/imunologia , Vacinação , Vacinas de DNA/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
3.
Apoptosis ; 2(1): 61-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-14646565

RESUMO

Haematologic abnormalities accompany the majority of HIV-1 infections. At present it is unclear whether this is due directly to HIV infection of hematopoietic progenitor cells, or whether this results from an indirect mechanism secondary to HIV infection. Here we provide evidence for an indirect mechanism, whereby hematopoietic progenitor cells undergo HIV gp120-induced apoptosis (programmed cell death) even in the absence of HIV infection. Freshly isolated, purified human hematopoietic progenitor CD34+ cells, derived from both umbilical cord blood and bone marrow, co-expressed the CD4 marker at low density on their surface. Although these CD34+CD4+ cells theoretically should be capable of productive infection by HIV, we found that HIV-IIIB could not establish productive infection in these cells. Nonetheless, gp120 from IIIB could bind the cells. Thus, binding of gp120 did not correlate with infectivity. Furthermore, binding of gp120 was a specific event, leading to apoptosis upon crosslinking with anti-gp120 through a fas-dependent mechanism. If apoptosis is also observed in vivo even in uninfected hematopoietic cells, this could contribute significantly to the impairment in hematopoietic cell number and function. Our data suggest a novel indirect mechanism for depletion of CD34+ and CD34+-derived cells even in the absence of productive viral infection of these cells.

4.
J Infect Dis ; 174(4): 866-9, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8843232

RESUMO

The effect of maternally transferred monoclonal antibody (MAb) on the offspring antibody response to rgp120SF2 was examined in a murine model. Two MAbs were studied: MAb 83.1, which recognizes a determinant in the V3 loop of gp120 from human immunodeficiency virus-1 (HIV-1) SF2, and MAb 26.2D3, which recognizes a conserved N-terminal region of gp120 from HIV-1SF2. Offspring were immunized at 18-21 days of age with 100 micrograms of rgp120SF2 in complete Freund's adjuvant. Offspring immunized in the presence of preexisting MAb 83.1 but not MAb 26.2D3 demonstrated inhibition of the IgG anti-V3 response. The total IgG anti-rgp120SF2 response was not affected by preexisting MAb. Since newborns at risk for HIV may be immunized in the presence of maternal or administered anti-HIV antibody, alternative strategies may be required to circumvent inhibition of the infant's epitope-specific response to HIV immunization by preexisting antibody.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , Imunidade Materno-Adquirida , Vacinas Sintéticas/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Feminino , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Gravidez
5.
AIDS Res Hum Retroviruses ; 12(14): 1341-8, 1996 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-8891113

RESUMO

A large stock preparation of the HIV-1SF2 isolate has been derived after serial passage in human peripheral blood mononuclear cells (PBMCs). This viral stock has a titer of 10(4.9) TCID50 in human PBMCs and 10(4.2) TCID50 in chimpanzee PBMCs. By inoculation into animals the 50% chimpanzee infectious dose titer was found to be about 10(2.3). Virus isolation from animals was achieved on most occasions within 1-4 weeks after inoculation and then became transient. Viral RNA and DNA PCR analyses confirmed the virus infection of the chimpanzees. Anti-HIV antibody levels in the inoculated animals ranged from 1:400 to 1:6400 as measured by ELISA. About 680 vials of this stock preparation, frozen at -190 degrees C, are available for future studies of vaccines and antiviral therapies.


Assuntos
Vacinas contra a AIDS , HIV-1 , Animais , DNA Viral/química , Ensaio de Imunoadsorção Enzimática , HIV-1/patogenicidade , Humanos , Pan troglodytes , Reação em Cadeia da Polimerase , RNA Viral/química
6.
J Acquir Immune Defic Syndr Hum Retrovirol ; 11(1): 95-104, 1996 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8528739

RESUMO

A flow cytometric assay based on expression of the activation antigen CD69 was developed to analyze immunological responses of T cells from human immunodeficiency virus (HIV)-infected (HIV+) or HIV-seronegative (HIV-) donors after in vitro simulation by antigens and polyclonal activators. The levels of CD69 on freshly-isolated or unstimulated, cultured CD3+, CD4+, or CD8+ peripheral blood lymphocyte (PBL) subsets were low and did not differ greatly between HIV+ and HIV- donors. The frequencies of CD3+, CD4+, and CD8+ lymphocytes from HIV+ donors that expressed CD69 after culture with antigenic or mitogenic stimuli were significantly lower than in HIV- donors. Comparison of CD69 expression with [3H]thymidine incorporation revealed that both assays could detect lymphocyte responses to antigenic or mitogenic stimuli. The CD3+ PBL from HIV+ or HIV- donors did not show increased CD69 expression after culture with soluble or cross-linked recombinant envelope glycoprotein, gp120. The gp120, however, significantly inhibited CD69 expression in phytohemagglutinin-stimulated T cells in vitro and may also affect T-cell activation in vivo. These studies demonstrate the usefulness of this CD69 expression assay for the rapid assessment of defects in immune responses of phenotypically defined lymphocyte subsets in HIV+ patients and for testing the effects of agents that modulate immune activation.


Assuntos
Antígenos CD/biossíntese , Antígenos de Diferenciação de Linfócitos T/biossíntese , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Ativação Linfocitária , Complexo CD3/imunologia , Células Cultivadas , Replicação do DNA , Citometria de Fluxo , Proteína gp120 do Envelope de HIV/farmacologia , Soropositividade para HIV/imunologia , Humanos , Imunofenotipagem , Lectinas Tipo C , Ativação Linfocitária/efeitos dos fármacos , Masculino , Mitógenos/farmacologia , Estudos Prospectivos , Proteínas Recombinantes , Timidina/metabolismo
7.
AIDS ; 9(12): 1313-22, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8605050

RESUMO

OBJECTIVE: To determine whether vaccination with recombinant HIV-1SF2 gp120 in a novel oil-in-water adjuvant emulsion, MF59, protects chimpanzees against challenge with HIV-1SF2, the homologous virus isolate. METHODS: Two vaccinated chimpanzees and two control animals were challenged with 25-50 animal infectious doses of a stock of HIV-1SF2 that had been grown in mitogen-activated human peripheral blood mononuclear cells (PBMC). The animals were monitored by a series of serologic [enzyme-linked immunosorbent assay (ELISA), Western blot, and neutralization assays] and virologic [virus culture, RNA and DNA polymerase chain reaction (PCR)] assays for infection. RESULTS: Both control animals showed evidence of seroconversion in ELISA and Western blot assays. In addition, virus was detected in the early, acute phase of infection of both control animals by (1) plasma RNA PCR, (2) virus culture, and (3) PBMC DNA PCR assays. One vaccinated animal showed no serologic or virologic evidence of infection. The other vaccinated animal has not seroconverted, and there was no evidence of plasma viremia. However, virus was detected at early timepoints in this animal's PBMC, and transient lymphoproliferation to HIV-1 proteins not in the vaccine was observed. These observations suggest that the former animal was protected from challenge while the latter may have experienced a transient or curtailed infection. CONCLUSION: Two types of vaccine-induced protective immune responses were observed when chimpanzees immunized with rgp120SF2 were challenged with the homologous virus isolate: a response consistent with the 'sterilizing immune response' documented in the chimpanzee model in previous studies, as well as one that did not completely protect from infection, showing curtailment of the acute phase and a failure of the animal to seroconvert.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Vacinação , Vacinas Sintéticas/uso terapêutico , Sequência de Aminoácidos , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Ativação Linfocitária , Dados de Sequência Molecular , Testes de Neutralização , Pan troglodytes , Reação em Cadeia da Polimerase , Cultura de Vírus
8.
J Infect Dis ; 172(2): 539-42, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7622900

RESUMO

A murine model was developed for assessing the effects of passively transferred polyclonal maternal anti-gp120 antibodies on the subsequent immunization of the offspring with recombinant gp120SF2 in complete Freund's adjuvant (rgp120SF2-CFA). Adult female BALB/c mice were immunized with rgp120SF2-CFA 6 weeks before mating. The 3-week-old offspring were subsequently immunized with the same vaccine and followed for 9 weeks. Both the total IgG anti-rgp120SF2 and the anti-V3 IgG antibody response to vaccine were inhibited in the experimental animals. The total IgG anti-rgp120SF2 response was < 20% of the control response (P < .001) 9 weeks after immunization. Anti-V3 antibody was also decreased. As vaccine studies begin in infants, the effects of preexisting antibody on the infant response to human immunodeficiency virus vaccines must be considered.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Antivirais/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , Imunidade Materno-Adquirida/imunologia , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Feminino , HIV-1/imunologia , Imunização Passiva , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Proteínas Recombinantes/imunologia
9.
J Infect Dis ; 171(5): 1343-7, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7751714

RESUMO

A vaccine breakthrough occurred in a phase 1 clinical trial of a human immunodeficiency virus (HIV) type 1 candidate subunit vaccine. The vaccine antigen, gp120SF2, is a fully glycosylated protein produced in mammalian cells from the HIVSF2 isolate. After 4 immunizations, the subject developed neutralizing antibodies and lymphoproliferative responses to the gp120 protein. About 18 weeks after the last immunization, the subject became HIV infected. During the acute phase of infection, there was high virus burden, a decline in CD4+ T lymphocytes, increases in rgp120SF2-binding antibodies and HIVSF2- and HIVMN-neutralizing antibodies, and transient lymphoproliferative responses to HIV-1 envelope and core proteins. The nucleotide sequence of the V3 loop from 2 virus isolations displayed close similarity to the V3 sequence of the vaccine antigen. Thus, the immunologic responses induced by the vaccine in this subject did not protect him from HIV-1 infection.


Assuntos
Vacinas contra a AIDS/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Sequência de Aminoácidos , Contagem de Linfócito CD4 , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina , Humanos , Imunidade Ativa , Masculino , Dados de Sequência Molecular , Testes de Neutralização , Fragmentos de Peptídeos/genética , RNA Viral/sangue , RNA Viral/genética , Análise de Sequência de DNA , Vacinação
10.
J Infect Dis ; 170(5): 1288-91, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7963729

RESUMO

A phase 1 study of 42 non-human immunodeficiency virus type 1 (HIV)-infected volunteers was initiated to determine the safety and immunogenicity of an HIV subunit vaccine consisting of recombinant envelope gp120 derived from HIVSF2 (rgp120SF2) combined with a novel adjuvant, MF59, with or without the immunomodulator muramyl tripeptide dipalmitoyl phosphatidylethanolamine (MTP-PE). All injections contained adjuvant MF59, and subjects were grouped according to MTP-PE dose. Injections were given on days 0, 30, 180, and 365. The vaccine was well tolerated with limited local and systemic reactions. These immunizations induced rgp120SF2-specific binding antibodies that persisted > or = 24 weeks. After three immunizations, all subjects receiving the antigen developed neutralizing antibodies to HIVSF2, and serum from 67% of these subjects also cross-neutralized HIVMN. ELISA-reactive antibodies to the HIVSF2 V3 region and strong lymphoproliferative responses to HIVSF2 envelope proteins were detected in all rgp120SF2-immunized subjects.


Assuntos
Vacinas contra a AIDS/imunologia , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adjuvantes Imunológicos/administração & dosagem , Proteína gp120 do Envelope de HIV/imunologia , Fosfatidiletanolaminas/administração & dosagem , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas contra a AIDS/administração & dosagem , Acetilmuramil-Alanil-Isoglutamina/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Feminino , Anticorpos Anti-HIV/sangue , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Vacinas Sintéticas/administração & dosagem
11.
Eur J Immunol ; 24(10): 2369-76, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7523139

RESUMO

Priming of CD8+ cytotoxic T lymphocyte (CTL) responses with recombinant proteins has been facilitated by the development of novel adjuvants that deliver antigens into the class I major histocompatibility complex (MHC) pathway. However, the extent to which secondary structure or glycosylation of these proteins prevents priming of class I MHC-restricted CTL responses is not clear. To address this issue, recombinant HIV-1 gp120 envelope proteins produced in yeast insect, or mammalian cells were compared for the ability to elicit CD8+ CTL activity in mice. Envelope-specific CD8+ T lymphocytes were detected in BALB/c mice immunized with env 2-3, a 55-kDa yeast-derived envelope protein that is not glycosylated and lacks a native conformation. This response was directed against a previously described epitope in the V3 region of gp120, as well as a newly identified epitope located near the carboxy-terminus of the molecule. Similar levels of V3-directed CTL activity were observed in mice immunized with recombinant gp120 produced in insect (Spodoptera fugiperda) cells using a baculovirus expression system (gp120BAC). In contrast, induction of CTL responses was considerably less efficient when mice were immunized with gp120CHO, a native, fully glycosylated envelope protein produced in mammalian CHO cells. Denaturation of gp120CHO prior to immunization was not sufficient to prime CTL responses. However, envelope-specific CD8+ CTL activity was elicited when N-linked glycans were removed by treatment with an endoglycosidase. Possible mechanisms by which N-linked glycans influence delivery or processing of recombinant proteins for class I MHC presentation, and the implications of these findings for the design of subunit vaccines, are discussed.


Assuntos
Glicoproteínas/imunologia , Proteína gp120 do Envelope de HIV/química , HIV-1/imunologia , Proteínas Recombinantes/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Animais , Citotoxicidade Imunológica , Epitopos , Feminino , Proteína gp120 do Envelope de HIV/imunologia , Imunidade Celular , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Peptídeos/química , Proteínas Recombinantes/química , Relação Estrutura-Atividade
12.
Vaccine ; 12(10): 885-94, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7975829

RESUMO

We have described previously the generation of seven HIV-SF2 Nef-specific, CD4+ T-cell clones, identification of epitopes within which are recognized by these clones, and the MHC alleles that restrict their responses. In this study, we have extended this characterization to include evaluation of antigen-processing and presentation requirements and cytotoxic activity. Clones were generated from five HIV-1 uninfected donors by in vitro stimulation of peripheral blood mononuclear cells with purified recombinant Nef1. In experiments with fixed cells, with the exception of two clones, recognition of Nef, but not Nef peptides, required processing. Also, at higher concentrations of antigen, the clones themselves were capable of presenting Nef peptides, but not soluble Nef. All clones had the ability to specifically lyse autologous, Epstein-Barr virus-transformed lines sensitized with Nef synthetic peptides, or, in some cases, soluble Nef. The cytotoxic activity mapped to the same epitopes identified for the proliferative response (a.a. 14-22, 47-53, 68-77, 70-77, 195-203 and 185-192) and was restricted by the same HLA class II molecules (DRw6, DQw7, DRw15(2), DR1 and DP5). Sensitization of the cytolytic clones with specific Nef peptides, but not soluble Nef, resulted in autolysis.


Assuntos
Apresentação de Antígeno , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica , Produtos do Gene nef/imunologia , HIV-1/imunologia , Alelos , Sequência de Aminoácidos , Células Cultivadas , Células Clonais , Genes MHC da Classe II , Humanos , Ativação Linfocitária , Dados de Sequência Molecular , Proteínas Recombinantes/imunologia , Linfócitos T Citotóxicos/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
13.
Vaccine ; 12(2): 117-28, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7511861

RESUMO

Human T-cell clones with specificity to the HIV-1 nef protein were generated by the in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-seronegative donors with purified nef from the HIV-SF2 isolate produced in genetically engineered yeast. Here the characterization is described of a total of seven discrete clones derived from five different donors. Each clone was CD3+ CD4+ CD8- as determined by FACS analysis. The epitopes recognized by these clones were identified using synthetic overlapping peptides spanning the entire length of nef. Six discrete helper T-cell epitopes located in five distinct regions of nef were identified by this approach. Three of these epitopes are more than 80% conserved among all HIV-1 nef proteins for which sequence data are available. The remaining epitopes are in regions of nef that vary among isolates. Many of the epitopes recognized by our clones overlap T-cell epitopes identified by others examining T-cell responses to nef in HIV-1-infected patients and immunized animals. Using partially class II-matched EBV-transformed B-cell lines, we were able to identify five different HLA class II alleles which encode restricting elements for the in vitro nef-specific proliferative response of these clones (DR1, DRw15(2), DRw6, DQw7, DP5).


Assuntos
Linfócitos T CD4-Positivos/imunologia , Produtos do Gene nef/imunologia , HIV-1/imunologia , Adulto , Sequência de Aminoácidos , Células Clonais/imunologia , Reações Cruzadas , Epitopos/genética , Produtos do Gene nef/genética , Soronegatividade para HIV/imunologia , HIV-1/genética , Antígenos de Histocompatibilidade Classe II , Humanos , Técnicas In Vitro , Ativação Linfocitária , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
14.
J Acquir Immune Defic Syndr (1988) ; 5(10): 1005-8, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1280682

RESUMO

This report compares the immunogenicity of three different preparations of gp120 [the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virus]: (a) native, fully glycosylated gp120; (b) a nonglycosylated, denatured form of gp120; and (c) a nonglycosylated peptide representing the "immunodominant" third hypervariable region of the gp120 molecule. Results indicate that the native glycosylated form of gp120 induces a maximal anti-HIV response in which a majority of B cells bind to conformation-dependent epitopes but less than one-fifth recognize the V3 loop region.


Assuntos
Formação de Anticorpos , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Animais , Linfócitos B/imunologia , Células CHO , Cricetinae , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Feminino , Variação Genética , Glicosilação , Anticorpos Anti-HIV/análise , Anticorpos Anti-HIV/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Conformação Proteica , Desnaturação Proteica
16.
J Gen Virol ; 73 ( Pt 5): 1099-106, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1375277

RESUMO

Chimpanzees infected with human immunodeficiency virus type 1 produce antibodies against the variable regions of the external envelope glycoprotein gp120. All five variable regions contain an epitope which is recognized by at least one of five chimpanzee sera. Each of the sera recognized a different pattern of epitopes. It is suggested that this varying response contributes to the emergence of variant viruses in the host. In contrast with the variability of the chimpanzees' response to replicating virus, that of baboons to a candidate recombinant vaccine is more uniform. Baboons injected with recombinant gp120 produced high levels of antibodies to epitopes within both the variable and conserved regions which coincided with epitopes previously shown to induce neutralizing antibodies.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Epitopos/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , HIV-1/imunologia , Animais , Formação de Anticorpos , Especificidade de Anticorpos , Pan troglodytes , Papio , Fragmentos de Peptídeos/imunologia , Proteínas Recombinantes/imunologia , Vacinas Sintéticas
17.
J Med Primatol ; 21(2-3): 82-90, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1433271

RESUMO

Sera from SIV-infected macaques were found to contain antibodies that reacted with conformation-dependent, group-specific determinants on the SIV envelope protein gp130. These conformation-dependent antibodies exhibited virus neutralizing activity; their presence was associated with protection in vaccine studies. The properties of these antibodies are quite similar to those that have been identified in sera from HIV-infected human subjects. These data suggest that the SIV envelope gp130 remains a candidate for subunit vaccine studies.


Assuntos
Anticorpos Antivirais/sangue , Macaca , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Western Blotting , Células CHO , Cricetinae , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , HIV-1/imunologia , Soros Imunes/imunologia , Testes de Neutralização , Ensaio de Radioimunoprecipitação , Proteínas Recombinantes/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia
18.
J Virol ; 66(1): 172-82, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1727480

RESUMO

The protection of individuals from human immunodeficiency virus type 1 (HIV-1) infection with an envelope subunit derived from a single isolate will require the presentation of conserved epitopes in gp120. The objective of the studies presented here was to test whether a native recombinant gp120 (rgp120) immunogen would elicit responses to conserved neutralization epitopes that are not present in a denatured recombinant gp120 antigen from the same virus isolate. In a large study of 51 baboons, we have generated heterologous neutralizing activity with native, glycosylated rgp120SF2 but not with denatured, nonglycosylated env 2-3SF2. After repeated exposure to rgp120SF2 formulated with one of several adjuvants, virus isolates from the United States, the Caribbean, and Africa were neutralized. The timing of the immunization regimen and the choice of adjuvant affected the virus neutralization titers both quantitatively and qualitatively. These results suggest that vaccination with native, glycosylated rgp120 from a single virus isolate, HIV-SF2, may elicit a protective immune response effective against geographically and sequentially distinct HIV-1 isolates.


Assuntos
Anticorpos Anti-HIV/biossíntese , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Testes de Neutralização , Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos , Sequência de Aminoácidos , Animais , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Glicosilação , Antígenos HIV/imunologia , Imunização Passiva , Imunização Secundária , Cinética , Estudos Longitudinais , Dados de Sequência Molecular , Papio , Fragmentos de Peptídeos/imunologia , Desnaturação Proteica , Proteínas Recombinantes/imunologia , Vacinas Sintéticas/imunologia
19.
Science ; 254(5028): 105-8, 1991 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-1718036

RESUMO

The spectrum of human immunodeficiency virus type 1 (HIV-1) isolates neutralized by antibodies from HIV-1-infected humans is broader than the spectrum of isolates neutralized by sera from animals immunized with purified gp120 subunits. This broader neutralization was due, in part, to the presence of antibodies to conserved gp120 conformational epitopes. Purified conformation-dependent gp120-specific human antibodies neutralized a wider range of virus isolates than human antibodies directed to linear determinants in gp120 and were also responsible for the majority of the gp120-specific CD4-blocking activity of HIV-1-infected human sera. A gp120 subunit vaccine that effectively presents these conformation-dependent neutralization epitopes should protect against a broader range of HIV-1 variants than a vaccine that presents exclusively linear determinants.


Assuntos
Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Sequência de Aminoácidos , Especificidade de Anticorpos , Epitopos , Produtos do Gene env/imunologia , Anticorpos Anti-HIV/química , Proteína gp120 do Envelope de HIV/química , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Testes de Neutralização , Conformação Proteica , Relação Estrutura-Atividade
20.
J Virol Methods ; 34(2): 173-80, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1687144

RESUMO

An HeLa-LAV cell line was established by infecting and subcloning previously described CD4-expressing HeLa cells with HIV-1. Cells of this line stably synthesize all major HIV proteins, release infectious particles of HIV-1, but do not die even after long term culture. More than 90% of the cells express the envelope protein gp120 on the surface. The cells can be easily and efficiently labeled with 51chromium, and exhibit a low spontaneous release. Because they are susceptible to killing by allogeneic cytotoxic T cells (CTL) when targeted to gp120, they ought to be a useful source of target cells in any kind of HIV-specific killing assays. The cells may also help studies on HIV replication in non-lymphatic/non-monocytic cells. The HeLa-LAV cell line will be freely available from the AIDS Research and Reference Reagent Program.


Assuntos
HIV-1 , Células HeLa/microbiologia , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Células Cultivadas , Células Clonais , Citotoxicidade Imunológica , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Produtos do Gene gag/análise , Proteína gp120 do Envelope de HIV/análise , Células HeLa/imunologia , Humanos , Técnicas In Vitro , Linfócitos T Citotóxicos/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana
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