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1.
Int J Clin Pract ; 60(4): 450-6, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16620359

RESUMEN

Risk factors for invasive pneumococcal disease (IPD) include young and old age, comorbidities (such as splenic dysfunction, immunodeficiencies, chronic renal disease, chronic heart or lung disease or cerebral spinal fluid leak), crowded environments or poor socioeconomic conditions. Universal use of the 7-valent pneumococcal conjugate (7vPncCRM) vaccine for infants and young children has led to significant decreases in IPD in the vaccinated population (direct protection), and there has also been a decrease in the incidence of IPD among the nonvaccinated population (indirect immunity; herd protection). While 7vPncCRM vaccine is administered universally to children in USA, many countries of the European Union have chosen to target children with comorbidities. This review aims to highlight individual risk factors for IPD, describe studies that evaluated pneumococcal conjugate vaccines in at-risk groups and estimate the proportion of at-risk children who may have been vaccinated in the European Union since the 7vPncCRM vaccine was introduced, using UK as an example. Although immunisation targeting only children with comorbidities may achieve satisfactory results for a few, many otherwise healthy children at risk simply because of their age will be neglected, and herd protection might not be established.


Asunto(s)
Programas de Inmunización/normas , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Anciano , Preescolar , Humanos , Lactante , Infecciones Neumocócicas/epidemiología , Factores de Riesgo , Reino Unido/epidemiología , Vacunas Conjugadas/administración & dosificación
2.
Expert Rev Vaccines ; 3(4): 353-7, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15270633

RESUMEN

There is risk attached to the development of respiratory syncytial virus vaccines, live attenuated or otherwise, but without the acceptance of this risk by manufacturers, health providers and the public, the conclusion of successful Phase III trials may lie in the distant future.


Asunto(s)
Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Humanos , Recién Nacido , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Virus Sincitiales Respiratorios/genética , Virus Sincitiales Respiratorios/fisiología , Vacunas Sintéticas/inmunología
4.
Pediatr Infect Dis J ; 20(2): 153-9, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11224833

RESUMEN

BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children. This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC. Routine childhood vaccines, including DTP, were coadministered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers. It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children.


Asunto(s)
Vacunas Bacterianas/inmunología , Meningitis Meningocócica/prevención & control , Neisseria meningitidis/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/efectos adversos , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunización Secundaria , Inmunoglobulina G/inmunología , Lactante , Masculino , Meningitis Meningocócica/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Seguridad , Sepsis/inmunología , Sepsis/prevención & control , Estados Unidos , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología
5.
Viral Immunol ; 13(1): 49-56, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10733168

RESUMEN

The safety and immunogenicity of four different regimens of CHIRON cytomegalovirus (CMV) gB subunit vaccine combined with MF59 adjuvant and administered to seropositive plasma donors were evaluated to ascertain whether vaccination of seropositive subjects would significantly increase antibody titer to gB glycoprotein. This was done to select the best vaccination regimen for generating high-titered plasma for manufacture of CMV immune globulin. No serious adverse events were attributed to this vaccine, and the vaccine was well tolerated. Only the first dose of vaccine in each regimen stimulated a four-fold or greater antibody response to gB glycoprotein and each regimen induced similar antibody titers. However, initial vaccination followed by a 1 week rest from plasmapheresis and two booster vaccinations at 8 and 24 weeks, each followed with another 1 week rest from plasmapheresis, maintained the highest geometric mean gB ELISA titer of the four regimens over the 34-week post-vaccination period. CMVIG manufactured from a pool of high titered plasma units from two of four subject groups had gB ELISA and neutralizing antibody titers nine and six times higher, respectively, compared to Cytogam, indicating that vaccination of seropositive subjects with CHIRON gB vaccine combined with MF59 adjuvant prior to harvesting plasma can enhance functional antibody in a CMVIG product.


Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Vacunación , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología , Adyuvantes Inmunológicos , Infecciones por Citomegalovirus/virología , Ensayo de Inmunoadsorción Enzimática , Humanos , Esquemas de Inmunización , Pruebas de Neutralización , Polisorbatos , Escualeno , Vacunas Virales/efectos adversos
6.
Pediatrics ; 101(4 Pt 1): 604-11, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9521941

RESUMEN

OBJECTIVE: To determine the safety and immunogenicity of heptavalent pneumococcal saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) individually conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of age. DESIGN: Two hundred twelve healthy 2-month-old infants were equally randomized to receive four consecutive doses of PNCRM7 or an investigational meningococcal group C conjugate vaccine, which served as a control. Concomitantly administered routine vaccines were oral polio vaccine and combined diphtheria toxoid, tetanus toxoid, and whole cell pertussis vaccine/Haemophilus influenzae type b vaccine consisting of capsular oligosaccharides conjugated to CRM197 (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vaccine or HbOC at 12 to 15 months. Active safety surveillance was conducted for 3 days after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes were measured by enzyme-linked immunosorbent assay prevaccination, after doses two and three, prebooster, and postbooster. RESULTS: Significantly fewer children experienced local reactions at the PNCRM7 injection site than at the DTP/HbOC site. There was no increase in the incidence or severity of local reactions at the PNCRM7 site with increasing doses of vaccine. Mild to moderate postvaccination fever was common in both the PNCRM7 and control vaccine groups, however DTP/HbOC was administered concurrently. All 7 vaccine serotypes were immunogenic. The kinetics of the immune responses were serotype-specific. After three doses of PNCRM7, between 92% to 100% of children had >/=0.15 microg/mL of antibody, and 51% to 90% achieved a level of >/=1 microg/mL against specific serotypes. A booster dose of PNCRM7 resulted in a brisk anamnestic response to all 7 vaccine serotypes, demonstrating effective stimulation of T-cell memory by the primary series of vaccinations. CONCLUSION: Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/inmunología , Vacunas Meningococicas , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Técnicas de Tipificación Bacteriana , Vacunas Bacterianas/administración & dosificación , Método Doble Ciego , Femenino , Vacuna Neumocócica Conjugada Heptavalente , Humanos , Inmunización Secundaria , Lactante , Masculino , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/clasificación , Estados Unidos , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos
7.
J Infect Dis ; 177(3): 634-41, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9498442

RESUMEN

Two different human vaccine trials examined interference arising from sequential administration of vaccines against heterologous alphaviruses. The first trial indicated that persons previously vaccinated against Venezuelan equine encephalitis virus (VEEV) exhibited poor neutralizing antibody responses to a live attenuated chikungunya virus (CHIKV) vaccine (46% response rate). The second trial prospectively examined neutralizing antibody responses to live attenuated VEEV vaccine in persons previously inoculated with either CHIKV vaccine or placebo. Following seroconversion to CHIKV, CHIKV vaccine recipients' geometric mean titers (GMTs) to VEEV by 80% plaque-reduction neutralization titration never exceeded 10, compared with a peak GMT of 95 after VEEV vaccination for alphavirus-naive volunteers who initially received placebo (P < .003). ELISA antibody responses demonstrated cross-reactive IgG to VEEV after primary CHIKV immunization and then an anamnestic response upon subsequent VEEV vaccination. These data indicate that preexisting alphavirus immunity in humans interferes with subsequent neutralizing antibody response to a live attenuated, heterologous vaccine.


Asunto(s)
Infecciones por Alphavirus/prevención & control , Anticuerpos Antivirales/sangre , Virus Chikungunya/inmunología , Virus de la Encefalitis Equina Venezolana/inmunología , Vacunas Virales/inmunología , Adolescente , Adulto , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Pruebas de Neutralización , Vacunación , Vacunas Atenuadas/inmunología , Interferencia Viral/inmunología
8.
Am J Hematol ; 57(2): 131-8, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9462545

RESUMEN

Intravenous immunoglobulin (IVIG) is an effective treatment for immune thrombocytopenic purpura (ITP) that induces transient blockade of the reticuloendothelial system (RES) with additional effects including alteration of T lymphocyte subsets and suppression of in vitro T lymphocyte proliferation. As anti-D also is an effective treatment for ITP, we investigated its in vitro and in vivo immunologic effects. The in vitro effects of various agents used in ITP therapy were compared using T lymphocyte proliferation assays. Anti-D caused significantly less inhibition than IVIG or dexamethasone, but non-specific protein was as suppressive as IVIG. Six children with chronic ITP were studied following anti-D administration. Patients received a single dose of anti-D (WinRho-SD, 50 microg/kg i.v. over 5 min) and were studied on day 0, day 7, and 1 month later. Anti-D did not affect T lymphocyte subsets including the T cell receptor variable beta repertoire, in vitro T lymphocyte proliferation to mitogens, recall antigens, or interleukin-2, in vitro IgG synthesis induced by pokeweed mitogen, or T lymphocyte cytokine mRNA levels. We conclude that anti-D has no demonstrable in vitro or in vivo effects on lymphocyte enumeration or function, and therefore likely is effective in the treatment of ITP primarily through RES blockade.


Asunto(s)
Inmunoglobulinas Intravenosas/administración & dosificación , Isoanticuerpos/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inmunología , Subgrupos de Linfocitos T/inmunología , Niño , Preescolar , Citocinas/inmunología , Humanos , Inmunofenotipificación , Lactante , Isoanticuerpos/inmunología , Isoanticuerpos/uso terapéutico , Globulina Inmune rho(D)
9.
Am J Trop Med Hyg ; 47(1): 98-103, 1992 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1322072

RESUMEN

Studies were conducted to determine the potential for transmission of a live, attenuated chikungunya (CHIK) virus vaccine by orally exposed or virus-inoculated mosquitoes. The vaccine (CHIK 181/clone 25) replicated in and was transmitted by female Aedes albopictus and Ae. aegypti after intrathoracic inoculation. Mosquitoes also became infected with the vaccine after ingesting virus from either a blood-soaked cotton pledget or a viremic monkey. However, because of the low viremias produced in inoculated humans, it is unlikely that mosquitoes would become infected by feeding on a person inoculated with the live, attenuated CHIK vaccine. Although the vaccine was transmitted by mosquitoes after intrathoracic inoculation, there was no evidence of reversion to a virulent phenotype.


Asunto(s)
Aedes/microbiología , Virus Chikungunya/inmunología , Insectos Vectores/microbiología , Infecciones por Togaviridae/transmisión , Vacunas Virales/efectos adversos , Animales , Animales Lactantes , Virus Chikungunya/patogenicidad , Virus Chikungunya/fisiología , Femenino , Macaca mulatta , Ratones , Vacunas Atenuadas/efectos adversos , Virulencia , Replicación Viral
10.
Vaccine ; 10(1): 39-42, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1539458

RESUMEN

Three healthy young men participating in phase 1 clinical vaccine trials had unexplained increases in their serum transaminase levels. Retrospective analysis indicated that these volunteers had participated in strenuous physical training 2-5 days prior to the noted elevations. The pattern of serum enzyme elevations, initially thought to be consistent with hepatic injury, were associated with parallel increases in creatine phosphokinase. One individual consented to repeat his exercise regimen. This was followed by a recurrence of the same pattern of increases in serum enzymes, including creatine phosphokinase. Thus, in trials where serum enzymes will be measured, it may be prudent to encourage subjects to refrain from increasing their activity above that which they normally perform.


Asunto(s)
Hepatopatías/enzimología , Esfuerzo Físico/fisiología , Rabdomiólisis/enzimología , Vacunas Atenuadas/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Creatina Quinasa/sangre , Humanos , L-Lactato Deshidrogenasa/sangre , Hepatopatías/etiología , Masculino , Estudios Retrospectivos , Rabdomiólisis/etiología
11.
Am J Trop Med Hyg ; 43(2): 219-26, 1990 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2389825

RESUMEN

To determine safety and immunogenicity, a single 0.5 ml dose of a monovalent live-attenuated dengue (DEN) 4 (341750 Carib) vaccine was given sc to 3 groups of flavivirus nonimmune volunteers in increasing concentrations. Two recipients received 10(3) plaque forming units (PFU)/dose (1:100 dilution of stock vaccine). One remained asymptomatic, but became viremic between days 12 and 15, experienced a mild elevation of temperature (37.4 degrees C), and developed DEN-4 specific antibody. Neither recipient of the 10(4) PFU became infected. Eight volunteers then received undiluted vaccine (10(5) PFU). Viremia and antibody (neutralizing, hemagglutination inhibition, and IgM) developed in 5 of the 8 (63%). These 5 volunteers also developed a scarcely noticeable macular, blanching rash and minimal temperature elevations (37.3, 38.1, 37, 37.9, and 37.9 degrees C). Clinically insignificant decreases in total white blood cell, lymphocyte, and polymorphonuclear cell counts and an elevation in mononuclear cell counts occurred in association with viremia. This vaccine is safe, reasonably immunogenic, and suitable for further evaluation.


Asunto(s)
Anticuerpos Antivirales/biosíntesis , Virus del Dengue/inmunología , Vacunas Virales/inmunología , Adulto , Dengue/etiología , Ensayo de Inmunoadsorción Enzimática , Pruebas de Inhibición de Hemaglutinación , Humanos , Immunoblotting , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/biosíntesis , Recuento de Leucocitos , Masculino , Pruebas de Neutralización , Vacunación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/normas , Vacunas Virales/efectos adversos , Vacunas Virales/normas , Viremia/etiología
12.
Antiviral Res ; 13(3): 139-49, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2353804

RESUMEN

The prophylactic efficacy of the broad-spectrum antiviral nucleoside analog ribavirin against flavivirus infection in non-human primates was investigated in a blinded, placebo-controlled study of rhesus monkeys infected with dengue virus. Both placebo- and ribavirin-treated monkeys developed viremia, as measured by direct plaque assay on Aedes albopictus C6/36 cells. Peak viremia occurred between days 3 and 9 after infection. No significant differences in time of onset, duration, or level of viremia were observed between placebo- and ribavirin-treated monkeys. Ribavirin induced predictable and reversible anemia and thrombocytosis. Serum ribavirin reached maximum levels of 30 microM by day 4, which approximates the in vitro minimum inhibitory concentration for dengue virus. Ribavirin appeared ineffective as a prophylactic drug for dengue type 1 viral infection, as evaluated by the magnitude of viremia in this monkey model.


Asunto(s)
Dengue/tratamiento farmacológico , Ribavirina/uso terapéutico , Ribonucleósidos/uso terapéutico , Animales , Macaca mulatta , Radioinmunoensayo , Ribavirina/sangre , Viremia
13.
Cancer Res ; 38(4): 969-77, 1978 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-205354

RESUMEN

The establishment of an epithelial cell line from a mouse pancreatic adenocarcinoma is described. The cell line, designated LTPA, was aneuploid and exhibited many transformed growth properties (rapid growth rate, failure to show density-dependent inhibition of growth, ability to grow in defined medium). A type C oncornavirus was isolated from the culture medium, and electron microscopy also revealed the presence of intracisternal type A particles. LTPA cells carried a persistent polyoma infection which produced only low levels of cytopathic effects. A mycoplasmal contamination was also carried. When injected s.c. into Swiss nu/nu mice, LTPA cells formed ductular structures which were destroyed by inflammatory reactions within 3 weeks.


Asunto(s)
Adenocarcinoma/microbiología , Neoplasias Pancreáticas/microbiología , Poliomavirus/aislamiento & purificación , Adenocarcinoma/genética , Adenocarcinoma/ultraestructura , Aneuploidia , Animales , Línea Celular , Femenino , Cuerpos de Inclusión Viral , Masculino , Ratones , Ratones Desnudos , Mycoplasma/aislamiento & purificación , Trasplante de Neoplasias , Neoplasias Experimentales/microbiología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/ultraestructura , Retroviridae/aislamiento & purificación , Trasplante Homólogo
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