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Biomedical subjects

M Giuliano

Publications and source records attributed to M Giuliano.

At least 19 recordsLinked to original sources
PubMed2006

Matrix metalloproteinase gene expression in oral lichen planus: erosive vs. reticular forms.

BACKGROUND: Oral lichen planus (OLP) is an autoimmune disease of unknown aetiology. The pathogenesis is characterized by apoptosis of basal keratinocytes, triggered by contact between CD8+ -activated lymphocytes and an unknown antigen expressed on the surface of the basal cells. Basement membrane (BM) degradation, which allows lymphocytes to migrate, involves proteolytic enzymes known as matrix metalloproteinases (MMPs). OBJECTIVES: This study aimed to evaluate the expression of a series of MMPs in biopsies from OLP patients, to reveal correlations with different clinical forms of OLP. METHODS: Twenty-six patients diagnosed with OLP (14 reticular and 12 erosive) were studied, together with seven healthy patients as negative controls. RESULTS: Reverse transcriptase polymerase chain reaction (RT-PCR) showed that the overall levels of expression of MMP mRNAs were higher in erosive lichen planus (E-OLP) than in the reticular forms (R-OLP). Moreover, MMP-1 and MMP-3 may be principally associated with erosion development. The expression of specific tissue inhibitors of metalloproteinases (TIMPs) was also evaluated. CONCLUSIONS: The different clinical appearances of OLP are associated with significant differences in MMP mRNA levels.

Aged↗
PubMed2005

Targeting HER2 as a therapeutic strategy for breast cancer: a paradigmatic shift of drug development in oncology.

Targeted therapies are causing a dramatic change in cancer drug development. Trastuzumab, a humanized recombinant monoclonal antibody that recognizes the extracellular domain of HER2 trans-membrane protein, is among the first target-specific drugs that have been licensed for clinical use and its development represents a model of integration of new agents with classical treatment strategies. In preclinical models, trastuzumab has demonstrated a marked antiproliferative effect and a synergistic action with several chemotherapeutic agents. Monotherapy trials indicate that trastuzumab is active as a single agent in HER2 positive patients, is well tolerated, and is associated with preservation of quality of life (QoL). Furthermore, as first line therapy for metastatic breast cancer overexpressing HER2 receptor, the addition of trastuzumab to taxane-based chemotherapy significantly increased rate of objective response, time to disease progression and survival when compared with chemotherapy alone. Trastuzumab has shown important activity when used with many chemotherapeutic agents such as platinum salts, gemcitabine, vinorelbine and capecitabine and liposomal anthracyclines. Various trials are now ongoing to optimize the use of trastuzumab and to investigate its role in the adjuvant and in the neo-adjuvant setting.

Animals↗
PubMed2004

Expression of Sulfolobus solfataricus alpha-glucosidase in Lactococcus lactis.

The industrial potential to use extreme thermophilic microorganisms and their enzymes lies in applications in which the temperature cannot be adjusted (cooled) at will. The production of enzymes from wild-type thermophiles is very low, therefore, for industrial applications, it is necessary to use recombinant microorganisms. In this paper, the cloning of a heat-stable alpha-glucosidase from Sulfolobus solfataricus using lactic acid bacteria as expression system is reported. The extremophilic alpha-glucosidase was cloned in Lactococcus lactis and correctly folded despite being expressed at a lower temperature. The recombinant cells were assayed for enzyme residual activity at 75 degrees C in order to analyze the direct use of whole cells as biocatalysts. Maximum activity corresponded to 40 U/l in static cultures. The protein yield was further improved by optimizing fermentation and reached 600 U/l in batch mode. Microfiltration led to an even higher enzyme production of 850 U/l as a result of increased biomass. The overall production of alpha-glucosidase using the engineered L. lactis strain in microfiltration fermentation is 1,000-fold higher than obtained using the wild-type.

Cloning, Molecular↗
PubMed2004

Macular coloboma in siblings affected by different phenotypes of retinitis pigmentosa.

Purpose To report the clinical association between macular coloboma (early-onset macular dystrophies/atrophic changes) and different phenotypes of retinitis pigmentosa (RP). Methods Three young-adult siblings, two males and one female, were retrospectively studied. These patients underwent two complete ophthalmologic examinations (27-month follow-up), including orthoptic evaluation, colour vision test, visual field, corneal topography, electronystagmography, fluorescein angiography, and electroretinography. Eye check, automated visual field test, and complete electroretinographic study were also conducted on other asymptomatic members of the same family. Results All symptomatic siblings were affected by manifest congenital nystagmus, poor visual acuity, and progressive visual field impairment in both eyes, bilaterally presenting macular coloboma associated with three different RP patterns: classic RP; mild dystrophy of the retinal pigment epithelium, associated with subnormal electroretinographic findings (subclinical form of RP); and sector RP. The ophthalmologic reports regarding their deceased father documented that he had suffered from the same alterations of ocular movements and visual performances diagnosing, in both eyes, extensive atrophic changes of the macular area completely surrounded by pigmented bone spicules (RP-type tapeto-retinal dystrophy). The other investigated relatives did not show any specific and/or significant ocular disorder. Conclusions In these three adult members of the same family, the concomitance between macular coloboma and different intrafamilial RP phenotypes is described. This association represents an autosomal dominant clinical entity, hitherto observed only in non familial sporadic cases.Eye (2004) 18, 421-428. doi:10.1038/sj.eye.6700689

Adult↗
PubMed2003

Macrophage-mediated clearance of cells undergoing caspase-3-independent death.

Little is known of the functions of caspases in mediating the surface changes required for phagocytosis of dying cells. Here we investigate the role played by the effector caspase, caspase-3 in this process using the caspase-3-defective MCF-7 breast carcinoma line and derived caspase-3-expressing transfectants. Our results indicate that, while certain typical features of apoptosis induced by etoposide--namely classical morphological changes and the ability to degrade DNA into oligonucleosomal fragments - are caspase-3-dependent, loss of cell adhesion to plastic and the capacity to interact with, and to be phagocytosed by, human monocyte-derived macrophages - both by CD14-dependent and CD14-independent mechanisms--do not require caspase-3. Furthermore, both etoposide-induced caspase-3-positive and -negative MCF-7 cells suppressed proinflammatory cytokine release by macrophages. These results demonstrate directly that cell surface changes that are sufficient for anti-inflammatory clearance by human macrophages can be regulated independently of stereotypical features of the apoptosis programme that require caspase-3.

Annexin A5↗
PubMed2002

Apoptosis induced in hepatoblastoma HepG2 cells by the proteasome inhibitor MG132 is associated with hydrogen peroxide production, expression of Bcl-XS and activation of caspase-3.

This report is focused on the apoptotic effect induced by MG132, an inhibitor of 26S proteasome, in human hepatoma HepG2 cells. The results were compared with those obtained with non-transformed human Chang liver cells. MG132 reduced the viability of HepG2 cells in a time- and dose-dependent manner. The effect was in tight connection with the induction of apoptosis, as indicated by fluorescence microscopy and cytometric analysis, and was accompanied by a remarkable increase in the production of H2O2 and a reduction in mitochondrial transmembrane potential (Deltapsim). In addition cell death was prevented by antioxidants such as GSH, N-acetylcysteine or catalase. Western blot analysis showed that HepG2 cells contain a very low level of Bcl-2 and a much higher level of Bcl-XL, another antiapoptotic factor of the same family. When the cells were exposed to MG132 the level of Bcl-XL diminished, while a new band, corresponding to the expression of the proapoptotic protein Bcl-XS was detected. MG132 also caused the release of cytochrome c from mitochondria and the activation of caspase-3 with the consequent degradation of poly-ADP ribose polymerase (PARP). The observation that the broad spectrum caspase inhibitor z-VAD markedly reduced the apoptotic effect of the drug clearly demonstrated that caspases play an important role in MG132-induced apoptosis. MG132 exerted a modest effect on the viability of Chang liver cells which primarily depended on the G2/M arrest of cell cycle while only a small percentage of apoptotic cells was found. The remarkable differences in the effects induced by MG132 in Chang liver cells and HepG2 cells made us hypothesise the potential use of proteasome inhibitors in hepatocarcinoma therapy.

Antineoplastic Agents↗
PubMed2001

pRb suppresses camptothecin-induced apoptosis in human osteosarcoma Saos-2 cells by inhibiting c-Jun N-terminal kinase.

This paper studies the cytotoxic effect induced by the topoisomerase I inhibitor camptothecin in human osteosarcoma Saos-2 cells, which lack p53 and contain a non-functional form of the product of the retinoblastoma gene, pRb. Cytotoxicity induced by camptothecin was dose- and time-dependent; the treatment with 100 nM camptothecin reduced cell viability by 50% at 32 h and by 75% at 72 h of exposure. The cytotoxic effect was caused by apoptosis, as ascertained by morphological evidence, acridine orange-ethidium bromide staining and flow cytometric analysis. Apoptosis was accompanied by both the activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase. Treatment with camptothecin caused a threefold increase in the activity of c-Jun N-terminal kinase (JNK) and an eightfold increase in the level of phosphorylated c-Jun. The introduction of the RB gene into Saos-2 cells reduced the rate of cell growth. Moreover, stable clones of transfected cells were resistant to camptothecin. Exposure to 100 nM camptothecin for 72 h reduced the viability of transfected cells by only 10%; moreover, very modest effects were observed on the activity of JNK as well as on the level of phosphorylated c-Jun. The results reported in this paper support the conclusion that the expression of wild-type pRb in Saos-2 cells exerts an anti-apoptotic influence through the control of JNK activity.

Apoptosis↗
PubMed2001

Enhancing the potency of peptide-pulsed antigen presenting cells by vector-driven hyperexpression of a triad of costimulatory molecules.

Recombinant orthopox vectors (both replication-defective fowlpox [rF], and replication competent vaccinia [rV] have been developed that simultaneously express three T-cell costimulatory molecule transgenes. The constituents of this triad of costimulatory molecules (designated TRICOM) are B7-1, ICAM-1, and LFA-3. We have previously shown that infection of murine dendritic cells (DCs) with TRICOM vectors increases their level of expression of the triad of costimulatory molecules and enhances the efficacy of DCs to activate T cells. While DCs are arguably the most potent antigen presenting cell (APC), limitations clearly exist in their use due to the level of effort and cost for their generation. The studies reported here demonstrate that a generic APC population, murine splenocytes, can be made markedly more efficient as APCs by infection with either rF-TRICOM or rV-TRICOM vectors. Infection of splenocytes with either TRICOM vector led to significant improvement of APC capabilities in terms of: (a) enhancement of mixed lymphocyte reactions; (b) a reduction in the amount of signal 1 to activate naive T cells; and (c) a reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. TRICOM-enhanced T-cell activation was shown to correspond to increases in type-1 cytokines and a reduced level of apoptosis, compared with T cells activated with uninfected or control vector-infected splenocytes. In vitro and in vivo experiments compared DCs with TRICOM-infected splenocytes. Infection of splenocytes with TRICOM vectors markedly enhanced their ability to activate T cells to levels approaching that of DCs. These studies thus demonstrate for the first time that an abundant and accessible population of APCs obtainable without lengthy culture or the use of costly exogenous cytokines (in contrast to that of DCs) can be made more potent as APCs with the use of vectors that express a triad of costimulatory molecules.

Animals↗
PubMed2001

Innovative fermentation strategies for the production of extremophilic enzymes.

A new type of microfiltration (MF) bioreactor, developed in our laboratory, was investigated for use in improving efficiency of the production of extremophilic enzymes. In spite of the difficulties in cultivating hyperthermophiles, we achieved, in 300 h fermentation, more than 38 g/l dry weight of Sulfolobus solfataricus using a MF technique, and we demonstrated that the activity of alcohol dehydrogenase (ADH), as the reporter enzyme, was not affected by cell density. However, hyperthermophile cultivation is difficult to scale up because of evaporation and the very low growth rate. Thus, to achieve high productivity we cultivated, in the MF bioreactor, recombinant mesophilic hosts engineered for the production of two thermophilic enzymes, namely, trehalosyldextrin-forming enzyme (SsTDFE) and trehalose-forming enzyme (SsTFE) from Sulfolobus solfataricus. The traditional Luria-Bertani broth used for recombinant Escherichia coli growth was replaced with a semidefined medium. The latter was used in both the batch and the MF experiments, and the ratio of complex components (e.g., yeast extract and tryptone) to a simple carbon source (glycerol) was decreased during the fed-batch phase to further decrease the medium cost in view of industrial applications. The bioprocess developed was able to improve productivity 500 fold for rSsTFE and 60 fold for rSsTDFE with respect to the wild type cultivated in MF mode. Comparisons with another recombinant enzyme, alpha-glucosidase (rSsalphagly), from Sulfolobus solfataricus produced in our MF bioreactor are reported.

Bioreactors↗
PubMed2001

Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect of combined treatment with the topoisomerase I-inhibitor topotecan.

Our results demonstrate that sodium phenylbutyrate, a compound with a low degree of toxicity, exerted a cytotoxic effect on human retinoblastoma Y79 cells in a time- and dose-dependent manner. Treatment of Y79 cells for 72 h with phenylbutyrate reduced cell viability by 63% at 2 mM and 90% at 4 mM. Cell death caused by phenylbutyrate exhibited the typical features of apoptosis, as shown by light and fluorescent microscopy. Western blot analysis demonstrated that exposure of Y79 cells to phenylbutyrate decreased the level of the antiapoptotic factor Bcl-2 and induced the activation of caspase-3, a key enzyme in the execution phase of apoptosis. Moreover, treatment with phenylbutyrate markedly increased the level of acetylated histone-H3. Combined treatment with phenylbutyrate and topotecan, a topoisomerase I-inhibitor, resulted in a clear synergistic effect. We suggest that the effects exerted by phenylbutyrate on Y79 cells essentially depend on modifications of gene expression consequent to histone hyperacetylation.

Acetylation↗
PubMed2000

Pleuropulmonary blastoma: management and prognosis of 11 cases.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor that affects children and adults. This neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that often demonstrates multidirectional differentiation. Despite the introduction of multimodal therapy, the prognosis of patients with PPB remains poor. METHODS: In the current study the authors reported on PPB cases from a national retrospective search performed in 18 Italian Associations for Pediatric Hematology and Oncology centers. Clinical data, surgical notes, pathologic findings, and summaries of chemotherapy and radiotherapy were obtained from reports and correlated with outcome by standard statistical methods. RESULTS: The series included 11 patients (7 boys and 4 girls) with a median age of 32 months. Respiratory distress was the most common clinical symptom. In three patients the PPB developed from other primary dysplastic diseases: cystic adenomatoid malformation in one case and congenital lung cysts in the other two cases. Five patients experienced disease recurrences (local recurrence in three patients and distant metastasis in two patients, within the central nervous system and an intraocular location, respectively). Patients with a type 2 histologic pattern and/or pleural involvement were found to have a worse outcome compared with patients without such features. Event free survival at 2 years from the time of diagnosis was 45% for all patients. Overall survival at 2 years was 72% for all patients. CONCLUSIONS: PPB is an aggressive neoplasm of early childhood and to the authors' knowledge no adequate therapy has been defined to date for patients with PPB. After making the diagnosis, the main goal of therapy should be radical surgery, even in patients with microscopic residual disease. Because the response to chemotherapy is poor, the authors' experience suggests that chemotherapy should be given with local radiotherapy in the majority of patients.

Child↗
PubMed2000

Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress.

Arachidonic acid administration caused apoptosis in Y79 cells, as shown by typical morphological changes, phosphatidylserine externalization, chromatin condensation, processing and activation of caspase-3 and cleavage of the endogenous caspase substrate poly-(ADP-ribose)-polymerase. Arachidonic acid also caused lamin B cleavage, suggesting caspase-6 activation. Arachidonic acid treatment was accompanied by increased formation of the lipid peroxidation end products malondialdehyde and 4-hydroxy-2-nonenal, lowering in reduced glutathione content and in mitochondrial membrane potential. Inhibiting glutathione synthesis sensitized Y79 cells to apoptosis-inducing stimuli, whilst replenishing reduced glutathione attenuated arachidonic acid toxicity. Similar findings were obtained using hydroperoxyeicosatetranoic acids (oxygenated metabolites of arachidonic acid which deplete the reduced glutathione pool) and nordihydroguaretic acid, a general inhibitor of lipooxygenase pathway. which may also trigger rapid depletion of reduced glutathione. Melittin, which is known to activate phospholipase A2, also potently induced apoptosis. Arachidonic acid toxicity was inversely related to cell density. This could depend on an increased production of molecules with antiapoptotic effect; insulin-like growth factors could most likely be one of these molecules. These results propose a role for oxidative stress in the cytotoxicity induced by arachidonic acid in Y79 cells and suggest that these cells could be protected from such toxicity as long as sufficient levels of reduced glutathione and survival factors are present.

Apoptosis↗
PubMed2000

Adenovirus-mediated wild-type p53 overexpression reverts tumourigenicity of human mesothelioma cells.

Pleural malignant mesothelioma (MM) shows poor survival, regardless of tumour stage at diagnosis. MM is unresponsive to present treatment regimens and new protocols are desperately needed. The localised nature, the potential accessibility, and the relative lack of distant metastases make MM a particularly attractive candidate for somatic gene therapy. A common target for cancer gene therapy is the tumour suppressor protein p53. p53 does not seem to be mutated or deleted in MM, but it can be inactivated by binding to other proteins, like mdm2 and SV40 large T antigen. We tested the effects of a replication-deficient adenoviral vector carrying wild-type p53 cDNA in human MM cells. Our results show that >95% of MM cells were efficiently infected with 25 multiplicity of infection (MOI) of vector. Wild-type p53 was effectively expressed resulting in >80% inhibition of proliferation in MM cells. AdCMV.p53 infection induced apoptosis while controls did not show any evident morphological alterations. Ex vivo p53 gene transfer experiments inhibited tumourigenesis in nude mice. In vivo, direct intratumour injection of AdCMV.p53 arrested tumour growth and prolonged survival of treated mice. These results indicate that p53-gene therapy should be strongly exploited for clinical trials in MM patients.

Adenoviridae↗
PubMed1999

The apoptotic effects and synergistic interaction of sodium butyrate and MG132 in human retinoblastoma Y79 cells.

This study deals with the apoptotic effect exerted on human retinoblastoma Y79 cells by both sodium butyrate and an inhibitor of 26S proteasome [z-Leu-Leu-Leu-CHO (MG132)] and their synergistic effect. Exposure to sodium butyrate (1-4 mM) induced an accumulation of cells in the G2-M phase that was already visible after 24 h of treatment, when morphological and biochemical signs of apoptosis appeared only in a small number of cells (5-10%). Thereafter, the apoptotic effects increased progressively with slow kinetics, reaching a maximum after 72 h of exposure, when they concerned a large fraction of cells (>75% with 4 mM sodium butyrate). Sodium butyrate stimulated the conversion of procaspase-3 into caspase-3 and also induced the cleavage of poly-(ADP-ribose) polymerase and lamin B, two hallmarks of apoptosis. All of the apoptotic signals were suppressed by benzyloxy carbonyl-Val-Ala-Asp-fluoromethylketone (a general inhibitor of caspase activities), whereas acetyl-Asp-Glu-Val-Asp aldehyde, a specific inhibitor of caspase-3 activity, only induced a partial reversion of the apoptotic effects. Sodium butyrate also decreased the Bcl-2 level, whereas it increased the Bax level and stimulated the release of cytochrome c from the mitochondria, an event that was most likely responsible for the activation of caspase-3. Finally, sodium butyrate activated 26S proteasome, the major extralysosomal degradative machinery, which is responsible for the degradation of short-lived proteins. Consequently, the levels of p53, N-myc, and IkappaBalpha (factors that play regulatory roles in apoptosis) diminished, whereas the nuclear level of nuclear factor kappaB concomitantly increased. Treatment of Y79 cells with MG132 induced apoptosis with more rapid kinetics than with sodium butyrate. The effects appeared after 8 h of incubation, reaching a maximum at 24 h, and they were accompanied by increased levels of N-myc, p53, and IkappaBalpha. MG132 also favored the release of cytochrome c from the mitochondria and increased the activity of caspase-3. When Y79 cells were exposed to combinations of sodium butyrate and MG132, the latter compound suppressed the decreasing effect induced by sodium butyrate on the levels of p53, N-myc, and IkappaBalpha and the increasing effect on the nuclear level of nuclear factor kappaB. Moreover, an increase in the level of Bax and an enhancement in the release of cytochrome c from the mitochondria were observed. Clear synergistic effects concerning the activation of both caspase-3 and apoptosis were induced by a combination of suboptimal doses of sodium butyrate and MG132. The results support the conclusion that MG132 potentiates the apoptotic effect of sodium butyrate by suppressing its stimulatory effect on 26S proteasome activity. Synergistic interactions between butyrate and inhibitors of proteasome could represent a new important tool in tumor therapy and, in particular, the treatment of retinoblastoma.

Apoptosis↗
PubMed1999

Generation and characterization of a novel single-gene-encoded single-chain immunoglobulin molecule with antigen binding activity and effector functions.

Monoclonal antibody (MAb) CC49 is a murine IgG1 that reacts with tumor-associated glycoprotein (TAG)-72, a pancarcinoma antigen. Clinical trials using radiolabeled CC49 for diagnostic imaging have demonstrated specific localization of more than 90% of carcinomas. The feasibility of adopting in vivo gene inoculation methods for antibody-based immunotherapy requires introduction and expression of two genes, encoding immunoglobulin (Ig) heavy and light chains, in a single cell to generate a functional antibody. To circumvent the problems inherent in this approach, we have constructed a single-gene encoding a single-chain immunoglobulin (SCIg) that, unlike previously developed SCIgs, contains all IgG domains. To construct the novel SCIg, the carboxyl end of the constant region of the chimeric (c) CC49 kappa chain is joined, via a 30 residue Gly-Ser linker peptide, to the amino terminus of the CC49 heavy chain. To our knowledge, neither a linker peptide this long nor a linkage between the constant light (C(L)) and variable heavy domains has been reported previously. Transfectomas developed by introducing the expression construct of the amplifiable gene in dihydrofolate reductase-deficient Chinese hamster ovary (CHO dhfr-) cells secrete a 160 kDa homodimeric molecule, SCIgcCC49. The in vitro antigen binding properties of SCIgcCC49 are comparable to those of cCC49 and SCIgcCC49deltaC(H)1, a single-chain Ig deficient in constant heavy chain-1 (C(H)1) and C(L) domains. The antibody-dependent cellular cytotoxicity (ADCC) of SCIgcCC49 and cCC49 were also comparable. This single-gene approach for generating an immunoglobulin molecule may facilitate in vivo gene inoculation as well as ex vivo transfection of patients' cultured tumor-infiltrating lymphocytes for immunotherapy protocols for a variety of diseases, including cancer.

Animals↗
PubMed1998

Antibody responses and persistence in the two years after immunization with two acellular vaccines and one whole-cell vaccine against pertussis.

OBJECTIVE: To evaluate the persistence of specific antibodies induced by primary immunization with three doses of two three-component acellular vaccines against pertussis with an observed efficacy of 84%, and one whole-cell vaccine with an observed efficacy of 36%. STUDY DESIGN: Serum samples were collected from a subsample of 1572 children from the Italian double-blind, placebo-controlled, randomized trial of vaccines used in 15,601 children at three time points: before administration of the first dose of vaccine, and 1 month and approximately 15 months after administration of the third dose. Further evaluation included pooled cross-sectional analysis of serum specimens associated with episodes of cough (which were not laboratory confirmed as pertussis infection) occurring among the entire population enrolled in the trial. RESULTS: With both acellular vaccines there was a fast and steep decrease in geometric mean antibody titers to pertussis toxin, filamentous hemagglutinin, and pertactin after vaccination. Mean titers were close to the limit of detection 15 months after primary immunization. The immunogenicity of the whole-cell study vaccine was poor 1 month after the third dose, and no antibody was detected in nearly all children 15 months after whole-cell vaccination. CONCLUSIONS: Although the study acellular pertussis vaccines induced a strong primary specific antibody response in almost all recipients, the duration of the response was limited. Sustained high-level production of antibody to the antigens tested does not account for the observed efficacy of acellular pertussis vaccines.

Animals↗
PubMed1998

Persistence of protection through 33 months of age provided by immunization in infancy with two three-component acellular pertussis vaccines. Stage II Working Group.

A large, randomized, placebo-controlled clinical trial in Italy on two three-component pertussis vaccines, given as DTaP in infancy, one manufactured by SmithKline and Beecham (SB) and one by Chiron Biocine (CB), found each vaccine to be 84% efficacious through the average age of 24 months. The cohort of children enrolled in the trial was followed with unmodified case ascertainment procedures for nine additional calendar months, during which partial unblinding occurred, for the unvaccinated randomized group. For the DTaP groups, the specific vaccine assignment remained double-blinded throughout the entire additional observation period. Pertussis was defined as paroxysmal cough lasting at least 21 days and confirmed by culture or serology. In the additional 9 months the observed absolute efficacy was 78% (95% CI, 62-87%) for SB DTaP vaccine and 89% (95% CI, 79-94%) for CB DTaP. The relative risk of developing pertussis in SB DTaP recipients compared to CB DTaP vaccinees was 1.99 (95% CI, 1.13-3.51). By combining observations from the initial and additional follow-up periods, the overall observed vaccine efficacy through an average age of 33 months of SB DTaP was 80% and of CB DTaP, 85%.

Child, Preschool↗