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Biomedical subjects

B Bizzini

Publications and source records attributed to B Bizzini.

At least 55 records · Page 3Linked to original sources
PubMed1993

Adjuvants--a balance between toxicity and adjuvanticity.

Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions. The most common adjuvants for human use today are still aluminium hydroxide, aluminium phosphate and calcium phosphate although oil emulsions, products from bacteria and their synthetic derivatives as well as liposomes have also been tested or used in humans. In recent years monophosphoryl lipid A, ISCOMs with Quil-A and Syntex adjuvant formulation (SAF) containing the threonyl derivative of muramyl dipeptide have been under consideration for use as adjuvants in humans. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side effects.

Adjuvants, Immunologic↗
PubMed1993

Envelope protein and p18(IIIB) peptide recognized by cytotoxic T lymphocytes from humans immunized with human immunodeficiency virus envelope.

Cytotoxic T cells are the main antigen-specific effector cells of the cellular immune system and MHC class I restricted cytotoxic T-lymphocyte (CTL) responses in mice, acting against the HIV-1 envelope protein, are known to be predominantly directed against an amino acid sequence in the third hypervariable domain. We have investigated the epitope specificity of anti-HIV-1 CTL in healthy human volunteers inoculated with a recombinant vaccinia expressing the HIV-1 gp160 envelope gene. Their isolated lymphocytes were stimulated in vitro with autologous HIV-1 infected cells. Our results show that immunization with recombinant virus is able to generate virus-specific CTLs to the HIV-1 gp160 envelope protein and to a 15-residue synthetic peptide corresponding to a highly variable region of the envelope p18(IIIB). The CTL response was restricted by class I MHC molecules HLA-A2 and A3 that commonly occur in the human population.

AIDS Vaccines↗
PubMed1993

Skin-window-induced inflammation in breast cancer patients: a study of macrophage migration.

A decreased number of macrophages has previously been demonstrated by means of skin-window assays in operable breast cancer patients. However, in this type of cellular inflammatory response, a varying intensity of cellular activation, cellular recruitment and macrophage chemotaxis exists. In this study, we performed skin windows after stimulation by a chemo-attractant (FMLP) and a recall antigen (Candidin-latex). Cellular responses were classified in 19 breast cancer patients according to the presence (A+) or absence (A0) of macrophage activation by comparison to healthy controls. In 13 A0 patients, the admixture of a cytokine (IFN alpha) and an immunomodulator (P40) to one agent or the other or both resulted in the restoration of macrophage functions. Our study shows that uniform cellular responses to chemo-attractants and antigens are observed in healthy and not immunocompromised individuals as assessed by skin-window tests. However, the cellular response recorded in immunodeficient cancer patients is altered. It also shows that the admixture to chemoattractants and antigens of particular cytokines or better still of an immunomodulator displaying a wide spectrum of activity offers a way of restoring macrophage functions. Individual responses to immunotherapy in clinical oncology may be related to such results.

Adjuvants, Immunologic↗
PubMed1992

Anti-infectious effect of C granulosum-derived P40 immunomodulator given by aerosolization and intranasal instillation.

It is known that C granulosum-derived P40 immunomodulator displays strong anti-microbial effects in mice by the intravenous route. Since microbial contamination of humans occurs in many instances via the airways, the effect of P40 on infections was investigated when it was given intranasally or by aerosolization. In order to augment its bioavailability, P40 was derivatized by coupling with polylysine chains (P40-PL). The results showed that P40-PL exercised a significant protective effect, both by the intranasal route and by aerosolization on both influenza and K pneumoniae infections produced by aerosolization or intranasal instillation. Stimulation of the phagocytic capacity of alveolar macrophages by these types of treatment is likely to account for the increased resistance of mice toward microbial infections.

Adjuvants, Immunologic↗
PubMed1992

Immunogenicity of combined anti-HIV and anti-suppressive vaccine preparations.

HIV-1 antigens generate in man both a humoral and cellular immune reaction. However, in ARC/AIDS patients, the cellular response is inhibited by HIV-1 which induces an antiproliferative (suppressive) effect on activated T cells. To overcome this inhibition and up-regulate the cellular response, we designed a new vaccine strategy directed both against HIV-1 and immunosuppression and we used an immunizing preparation composed of HIV-1 antigens combined with immunoregulatory peptides prepared in a biologically inactivated but immunogenic form. In mice, this preparation induced anti-HIV-1 antibodies and a cell-mediated cytotoxicity directed against H2 restricted cells carrying HIV-1 antigens.

Animals↗
PubMed1992

Induction of various cytokines in mice and activation of the complement system in rats as a part of the mechanism of action of the Corynebacterium granulosum-derived P40 immunomodulator.

The capacity of the Corynebacterium granulosum-derived P40 immunomodulator to induce in mice the formation of various cytokines IFN, IL-1, IL-2, alpha-TNF as well as to activate the complement system in rats was investigated. The results showed that P40 injected by the intravenous route was capable of inducing the formation of all four cytokines. High levels of IFN were measured 2 h after P40 stimulation and were still present at 24 h. The kinetic study of IL-1, IL-2 and alpha-TNF induction showed that it was a biphasic phenomenon. The patterns of IL-1 and alpha-TNF induction were quite comparable, whereas the release of IL-2 was delayed with respect to that of IL-1 and alpha-TNF. Oral administration of P40 to rats strongly activated the alternative pathway of the complement system. It was concluded that most of the non-specific effects of P40 on the immune system are likely to be mediated by its capacity to induce cytokine formation and to activate the complement system.

Adjuvants, Immunologic↗
PubMed1992

Assessment of the anti-viral effect of a short-term oral treatment of mice with live Saccharomyces cerevisiae cells.

For assessing the efficacy of antiviral treatments, influenza and herpes virus HSV-1 infections of varying degrees of severity have been produced. The infections proved to be reproducible with respect to both their course and death rate. These infections also exhibited a course slow enough to permit the assessment of treatments under conditions mimicking human infections and lent themselves to the choice of the best adapted strategy to treat an infection. A short-term oral treatment with live cells of S. cerevisiae was efficacious in protecting mice against mild influenza infection and partly but significantly against severe infection. On the other hand, it did not afford significant protection towards either mild or severe HSV-1 infections, but it significantly potentiated the effectiveness of the antiviral drug vidarabin. S. cerevisiae treatment induced the synthesis of IFN alpha but not that of TNF alpha.

Adjuvants, Immunologic↗
PubMed1992

Standardized mouse infection models as a way of evaluating the potency of anti-infectious agents.

Standardized bacterial and viral mouse infection models have been developed. Infections with extracellular bacteria (K. pneumoniae, S. pneumoniae, S. pyogenes A) were produced by either of two routes: via the intravenous route (i.v.) resulting in septicaemia and the intranasal route (i.n.) giving infections confined to the respiratory apparatus. Infections with intracellular bacteria (L. monocytogenes, S. typhimurium) were produced only by the i.v. route. Two types of viral infection, mild and severe, were produced. Infection with influenza virus was by aerosol and herpes virus HSV-1 by the intraperitoneal route. All infection models produced under strictly controlled conditions were shown to be characterized by a remarkable reproducibility regarding both the pattern of development and death rate. The infection models lend themselves to estimation of the efficacy of a drug as well as the designing of new therapeutic strategies.

Animals↗
PubMed1992

A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity.

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.

AIDS Vaccines↗
PubMed1992

One-year follow-up of vaccine therapy in HIV-infected immune-deficient individuals: a new strategy.

Immunization of AIDS/ARC patients with autologous cells expressing HIV antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of HIV-1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against HIV-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens.

AIDS Vaccines↗
PubMed1991

The effect of tetanus toxin on in vitro synaptogenesis.

Cultures of spinal cord neurons and cocultures of rat embryo neurons and muscle cells have been studied in the presence of tetanus toxin (TT) at a concentration of 40 micrograms/ml of medium. TT strongly stimulated neurite outgrowth, notably branching from the cell bodies. In addition it induced a marked, overall increase in acetylcholine receptor (AChR), but inhibited focalisation of AChR and acetylcholinesterase (AChE) at the synaptic sites. TT seems to act on neurite emergence, on the neuronal factor(s) controlling AChE and AChR concentrations, and on the factor(s) modulating degradation and/or synthesis of AChR.

Acetylcholinesterase↗
PubMed1991

Pneumococcal vaccination of elderly individuals.

Pneumococcal infections are still a cause of high morbidity and mortality in elderly populations. Since antibiotics are not wholly effective, vaccination should be performed. The response to pneumococcal vaccination of a limited group of elderly persons aged 60 to 90 years was studied. The sera of most individuals were found to contain antipneumococcal antibodies prior to vaccination. Vaccination resulted in antibody level increases in sera of all subjects except two. On the basis of antibody levels, 19 out of 20 vaccinees proved to be protected after vaccination. Combination of vaccination with a non-specific immunostimulation enhanced the antibody response.

Aged↗
PubMed1991

[The usefulness of vaccination in elderly persons].

The antitetanus, antipneumococcal and antiinfluenza immune status, as well as the efficacy of vaccination have been evaluated in the elderly. Ages of the studied populations ranged from 60 to 98 years. Before vaccination, only half of the tested population was found to be protected against tetanus. Immunization resulted in 80% coverage of this population. Prior to antipneumococcal vaccination, 32% of the tested sera did not contain a "potentially" protective antibody titre. Vaccination resulted in 100% seroconversion. It was verified that 100% of tested sera contained antibodies (greater than 10 U.H.A./ml) directed to the former Singapore antigen and 99.2% and 66.7%, respectively, to the newly immerged Shanghaï and Yamagata antigens (present in the administered vaccine). Following vaccination, 100% of the sera exhibited antibody titres higher than 10 U.H.A./ml to the Singapore and Shanghaï antigens, and 90.5% to the Yamagata antigen. It can be concluded from the reported results that antitetanus, antipneumococcal and antiinfluenza vaccinations should be systematically given to all individuals beyond 60 years of age, since these vaccinations are innocuous and confer extended vaccinal coverage.

Aged↗
PubMed1991

Usefulness of influenza vaccination in the elderly.

Since influenza morbidity and mortality are high in the elderly, the usefulness of vaccination has been evaluated. One hundred and twenty-six older persons aged 60-90 yr were given a vaccine consisting of the 3 antigens Singapore, Shanghaï and Yamagata, the latter 2 being new antigens. Antibody levels for each of the antigens were determined by ELISA calibrated in HA units prior to and 1 month after vaccination. Before vaccination, antibodies to Shanghaï and Singapore antigens were found in practically all sera tested, and antibodies to Yamagata antigen in only 66% of sera. After vaccination, significant levels of antibodies to all 3 antigens were found in sera tested. Thus, it was observed that influenza vaccination proved to be effective in the elderly. The elderly should be immunized against influenza, since this is a safe and efficacious preventive measure. In addition, vaccination should limit the spreading of influenza in nursing homes.

Aged↗
PubMed1990

Retrograde axonal transport of an exogenous enzyme covalently linked to B-IIb fragment of tetanus toxin.

Attempt to replace enzymes in a number of fatal lysosomal storage disease involving the central nervous system have as yet been unsuccessful owing to the impermeability of the blood/brain barrier to macromolecules. In order to treat storage disease due to enzyme deficiencies, we investigated the feasibility of transporting an enzyme into the central nervous system without crossing the blood/brain barrier. Using the B-IIb fragment of tetanus toxin (because it is involved in recognition by the nerve-cell endings), retrograde axonal transport toward the spinal cord and trans-synaptic movement, and glucose oxidase as a marker, we demonstrated that a non-toxic enzyme-vector conjugate was taken up by axon terminals. After injection into the gastrocnemius muscle, the B-IIb-glucose oxidase conjugate was detected, both histologically and electrochemically, distally to a ligature on the sciatic nerve. Thus the B-IIb fragment could serve as a vector for glucose oxidase transport into the central nervous system. It was also verified that the transported enzyme retained its activity. Transport of this 150 kDa molecule by fragment B-IIb of tetanus toxin suggests that other enzymes of a lesser molecular mass may also be transported.

Animals↗
PubMed1990

A dot-ELISA for the detection of IgG antibodies to mumps and varicella viruses.

An enzyme-linked immunosorbent assay using nitrocellulose strips (dot-ELISA) for the routine laboratory detection of IgG antibodies to mumps and varicella viruses is described. The virus antigens are dotted onto nitrocellulose strips, and the dotted strips are incubated with the sera to be tested. The bound antibodies are revealed using enzyme-labeled antihuman IgG antibodies. Reliable results are obtained when the assay is carried out at 37 degrees C. The reported data indicate that the dot-ELISA can reliably be used for the detection of IgG antibodies to mumps and varicella viruses in human sera.

Antibodies, Viral↗
PubMed1990

A dot-ELISA intended for the specific and simultaneous detection of antibodies directed to antigens derived from Toxoplasma gondii, rubella virus, cytomegalovirus, and type 1 and type 2 herpesviruses.

A procedure for the routine and simultaneous laboratory detection of IgG antibodies produced in humans in the course of various infectious diseases is described. The procedure, based on dot-enzyme-linked immunosorbent assay (ELISA), used single nitrocellulose strips onto which several antigens were dotted in close proximity. Optimal conditions were specified that allowed the unequivocal and simultaneous detection of IgG antibodies specifically directed against Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus type 1 and type 2 antigens. This technique has proved to be simultaneously specific, sensitive, and reliable, and it has been applied to prenatal screening of sera from pregnant women. It is suggested that this technique should also be used for the screening of large numbers of sera under field trial conditions.

Animals↗