Expressäo das proteínas p19 (gag) e gp21 (env) do HTLV-1 no tecido tireoidiano de pacientes com doença auto-imune da tireóide e no tecido tireoideano normal / Expression of p19 (gag) and pg21 (env) protein of HTLV-1 in thyroid tissue of patients with autoimmune disease of thyroid and in normal thyroid tissue

As doenças auto-imunes da tireóide säo os resultados da quebra da auto-tolerância causada principalmente por fatores genéticos e ambientais. O retrovírus HTLV-1 tem sido implicado como um importante fator ambiental desencadeador destas doenças. Objetivando encontrar evidências da participaçäo deste retrovírus, 47 tecidos tireoidianos parafinados de 45 pacientes com doença de Gravese dois com tireoidite de Hashimoto, juntamente com tecidos tireoidianos normais de seis tireóidesobtidos após necropsia e linfonodo de pacientes com infecçäo pelo HTLV-1, utilizados como controles negativo e positivo, respectivamente, foram estudados,. Com a intençäo de detectar as proteínas p19 (gag) E GP21 (env) do HTLV-1, os tecidos foram submetidos a imuno-histoquímica, utilizando-se um novo método de recuperaçäo antigênica e anticorpos monoclonais anti-19 e anti-gp21. Como resultado obtivemos a mediana do percentual de positividade no sexo feminino de 30 por cento e 41 por cento no masculino de 27 por cento e 52 por cento e total de 30 por cento e 41 por cento, para as proteínas p19 e gp21, respectivamente. Nos tecidos tireoidianos normais, cinco foram positivos para as duas proteínas e apresentaram mediana do percentual de positividade de 17 por cento para a p19 e 39 por cento para a gp21. A detecçäo das proteínas p19 e gp21 no tecido tireoidiano de pacientes com doenças auto-imune da tireóide e em tecidos normais talvez indique a expressäo genética de sequências do HTLV-1 integradas ao genoma dos indivíduos estudados, ou talvez possa representar mimetismo molecular, ou reaçäo cruzada, causada pela presença de antígenos comuns entre as proteínas P19 e gp21 do HTLV-1 e as células epiteliais foliculares da tireóide.

A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). The AGIS Group, and l'Agence Nationale de Recherche sur le SIDA.

The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group Network.

Recombinant gp160 derived from human immunodeficiency virus type 1 (HIV-1)IIIB and produced in mammalian tissue culture cells using a vaccinia virus expression system (rgp160-mam) was evaluated as a vaccine in combination with alum and deoxycholate adjuvant. Sixty low-risk, uninfected subjects received 12.5 micrograms, 50.0 micrograms, or adjuvant control at 0, 1, 6, and 12 months in a randomized, double-blind dose-escalation study. A single injection of 200 micrograms of vaccine was given at 18 months in an open study to 9 vaccines who had received 50 micrograms. The vaccine was safe. Six of 16 subjects receiving 50 micrograms developed neutralizing antibody to HIV-1IIIB. Seven of the 9 boosted with 200 micrograms of vaccine at 18 months developed neutralizing antibodies. Lymphocyte proliferation to rgp160-mam and baculovirus-derived rgp160 and rgp120 was induced in both groups (12.5 and 50.0 micrograms) and appeared after the first dose. Further studies with higher doses of rgp160-mam and vaccines derived from other strains of HIV-1 are warranted.

Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate.

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.

A phase I evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early human immunodeficiency virus infection. Military Medical Consortium for Applied Retroviral Research.

BACKGROUND: Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens. METHODS: We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored. RESULTS: In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell proliferative responses to gp160. Response was associated with the CD4 cell count determined before vaccination (13 of 16 subjects [81 percent] with greater than 600 cells per milliliter responded, as compared with 6 of 14 [43 percent] with less than or equal to 600 cells per milliliter; P = 0.07) and with the number of injections administered (87 percent of subjects randomly assigned to receive six injections responded, as compared with 40 percent of those assigned to three injections; P = 0.02). Local reactions at the site of injection were mild. There were no adverse systemic reactions, including diminution of general in vitro or in vivo cellular immune function. After 10 months of follow-up, the mean CD4 count had not decreased in the 19 subjects who responded, but it had decreased by 7.3 percent in the 11 who did not respond. CONCLUSIONS: This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.