Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Tuberculosis (Edinb) ; 93(2): 179-88, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23219236

ABSTRACT

UNLABELLED: Prevention of tuberculosis (TB) through vaccination would substantially reduce the global TB burden. Mtb72F/AS02 is a candidate TB vaccine shown to be immunogenic and well tolerated in PPD-negative adults. We evaluated the safety and immunogenicity of Mtb72F/AS02 in Mycobacterium-primed adults (BCG-vaccinated, or infected adults who had received post-exposure chemoprophylaxis or treatment for pulmonary TB disease). In this observer-blind controlled trial, 20 BCG-vaccinated adults and 18 adults previously infected with Mycobacterium tuberculosis (Mtb), were randomized 3:1 to receive three doses of Mtb72F/AS02 or AS02 at one-month intervals, and followed for 6 months post third vaccination. Mtb72F/AS02 was well tolerated in BCG-vaccinated adults, and tended to be more reactogenic in Mtb-infected adults. Adverse events were mainly self-limiting, resolving without sequelae. No serious adverse events were reported. The adverse events in Mtb72F/AS02 vaccinees were not clearly associated with vaccine-induced responses (as assessed by proinflammatory cytokines, total IgE and C-reactive protein levels). No Th2 T-cell responses, or vaccine-induced T-cell responses to Mtb antigens (CFP-10/PPD/ESAT-6) were detected by ICS. In both cohorts, Mtb72F/AS02 induced persistent polyfunctional Mtb72F-specific CD4(+) T-cell responses and anti-Mtb72F humoral responses. IFN-γ was detectable in serum one day post each vaccination. Further evaluation of the candidate vaccine, Mtb72F/AS02, is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00146744.


Subject(s)
Tuberculin/immunology , Tuberculosis Vaccines/immunology , Tuberculosis/immunology , Adolescent , Adult , Antibodies, Bacterial/biosynthesis , BCG Vaccine/immunology , CD4-Positive T-Lymphocytes/immunology , Dose-Response Relationship, Immunologic , Double-Blind Method , Female , Humans , Immunity, Cellular , Immunoglobulin G/biosynthesis , Interferon-gamma/biosynthesis , Male , Middle Aged , Mycobacterium tuberculosis/immunology , T-Lymphocyte Subsets/immunology , Tuberculosis Vaccines/administration & dosage , Tuberculosis Vaccines/adverse effects , Vaccination/adverse effects , Young Adult
2.
Infect Immun ; 73(12): 8017-26, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16299295

ABSTRACT

The C-terminal conserved region of Plasmodium falciparum merozoite surface protein 3 (MSP3) is the trigger antigen of a protective immune response mediated by cytophilic antibodies. In an open, randomized, two-adjuvant (Montanide ISA 720, aluminum hydroxide) phase I clinical trial we evaluated the safety and immunogenicity of increasing doses of a long synthetic peptide construct spanning the conserved region of MSP3 targeted by biologically active antibodies (MSP3-LSP). Thirty-five healthy volunteers were randomized to receive three subcutaneous injections on days 0, 30, and 120. Of the 100 injections given, 10 caused severe local reactions, 62 caused transient mild to moderate local reactions, and 28 caused no reaction. On the basis of preestablished exclusion criteria, use of the Montanide formulation led to withdrawal of five volunteers after the second injection. This led to a reduction in the subsequent vaccine doses in four of the groups. No vaccine-related serious adverse events occurred throughout the trial. After the third injection, volunteers displayed a marked specific anti-MSP3-LSP antibody response (23/30 individuals, compared with 29/34 individuals for plasma from an area where malaria is endemic), an anti-native MSP3 antibody response (19/30 individuals), a T-cell-antigen-specific proliferative response (26/30 individuals), and gamma interferon production (25/30 individuals). In conclusion, the MSP3-LSP vaccine was immunogenic with both adjuvants, although it was unacceptably reactogenic when it was combined with Montanide. The potential usefulness of the candidate vaccine is supported by the induction of a strong cytophilic response (i.e., the type of anti-MSP3 antibodies involved in antibody-dependent, monocyte-mediated protective mechanisms in areas where malaria is endemic).


Subject(s)
Antigens, Protozoan/immunology , Malaria Vaccines/adverse effects , Malaria Vaccines/immunology , Peptide Fragments/adverse effects , Peptide Fragments/immunology , Protozoan Proteins/immunology , Adult , Antibodies, Protozoan/blood , Antigens, Protozoan/administration & dosage , Antigens, Protozoan/adverse effects , Cell Proliferation , Cytokines/immunology , Female , Humans , Malaria Vaccines/administration & dosage , Male , Peptide Fragments/administration & dosage , T-Lymphocytes/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects , Vaccines, Subunit/immunology
3.
Vaccine ; 23(28): 3634-41, 2005 May 25.
Article in English | MEDLINE | ID: mdl-15882523

ABSTRACT

Cervical cancer results from cervical infection by human papillomaviruses (HPV), especially HPV16. Previous studies have shown that intramuscular vaccination of women with an HPV16 virus-like particle (VLP) vaccine induced a strong IgG response and protected against genital HPV16 infection. However, an alternative route of administration that avoids parenteral injection while inducing mucosal immunity might facilitate vaccine implementation in some settings, and partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. In this study, women were vaccinated with escalating doses of HPV16L1 VLPs via nasal nebulisation, bronchial aerosolisation, or a combination of intramuscular and aerosol vaccination. The alternative routes of vaccination were well tolerated and many of the volunteers who received aerosol vaccinations exhibited serum antibody titers that were comparable to those induced by intramuscular vaccination. A mucosal immune response was induced by aerosol vaccination as demonstrated by the induction of anti-HPV16 VLP IgA secreting cells in PBMC and SIgA in secretions. Our data suggest that aerosol administration of HPV VLPs may represent a potential alternative to parenteral injection.


Subject(s)
Immunity, Mucosal , Papillomaviridae/immunology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines , Respiratory Mucosa/immunology , Uterine Cervical Neoplasms/prevention & control , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Administration, Intranasal , Adolescent , Adult , Aerosols , Antibodies, Viral/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Injections, Intramuscular , Middle Aged , Viral Vaccines/adverse effects
5.
Graefes Arch Clin Exp Ophthalmol ; 242(11): 966-70, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15221302

ABSTRACT

PURPOSE: To compare in-season eotaxin-1 levels in tears of patients suffering from seasonal allergic conjunctivitis (SAC) with (1) tears of normal subjects and (2) tears of SAC patients out of season. METHODS: Tears of 11 SAC patients and six control volunteers were collected during the pollen season. Tears of five SAC patients showing a strong sensitivity to grass pollen (skin-prick tests and specific serum IgE) were collected both in season and out of season. ELISA measured eotaxin-1 level. RESULTS: Eotaxin-1 concentration in tears of SAC patients [2,100+/-503 (SEM) pg/ml] and normal subjects (1,193+/-176 pg/ml) were significantly different (P=0.0049). Regarding allergic patients, the clinical score (sum of five allergic criteria) was significantly different in season and out of season (P=0.0043) as was also the case with eotaxin-1 concentration (P=0.024). CONCLUSIONS: The eotaxin-1 concentration in tears of patients showing hay fever could confirm a diagnosis of seasonal ocular allergy.


Subject(s)
Chemokines, CC/metabolism , Chemotactic Factors, Eosinophil/metabolism , Conjunctivitis, Allergic/metabolism , Tears/metabolism , Adult , Chemokine CCL11 , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Prospective Studies , Seasons , Up-Regulation
SELECTION OF CITATIONS
SEARCH DETAIL
...