RESUMEN
This study compared a tetravalent DTaP-IPV vaccine (Di-Te-Ki-Pol vaccine "SSI") with the vaccination regimen used in Denmark at that time, DT-IPV plus wholecell pertussis vaccine. Two hundred and seventy children were included at their five-week routine examination. The children were allocated to one of the two vaccination regimens. No hypotonic-hyporesponsive episodes or other vaccine-related serious adverse events were seen. Local reactions, febrile and crying episodes following the investigational vaccine were similar to the reactions seen after Di-Te-Pol vaccine. All children achieved protective antibody levels to polio, diphtheria and tetanus after completing the vaccination schedule. A significantly better response to pertussis toxin was seen after the investigational vaccine. We conclude that the Di-Te-Ki-Pol vaccine is safe and immunogenic when used according to the schedule tested.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina , Vacuna contra la Tos Ferina , Anticuerpos Antibacterianos/análisis , Anticuerpos Antivirales/análisis , Dinamarca , Toxina Diftérica/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/normas , Humanos , Lactante , Recién Nacido , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/efectos adversos , Vacuna contra la Tos Ferina/normas , Seguridad , Toxina Tetánica/inmunologíaRESUMEN
The objective of this study was to investigate whether a tetravalent vaccine containing diphtheria, tetanus, monocomponent acellular pertussis and inactivated poliovirus (DTaP-IPV) was immunogenic and safe compared with the vaccination regime used in Denmark at the time of the study. The study was performed as an open controlled study in which 270 Danish children were enrolled at their 5 weeks' routine examination. The children were allocated to receive either (i) DTaP-IPV (12.5 Lf, 7 Lf, 40 microg, 40, 8, 32 DU) at 3, 5 and 12 months of age (n = 186) or (ii) DT-IPV (50 Lf, 12.5 Lf, 40, 8, 32 DU) at 5, 6 and 15 months of age plus whole-cell pertussis vaccine (> or = 4 IU) at 5 and 9 weeks and at 10 months of age (n = 84). No hypotonic hyporesponsive episodes or other vaccine-related serious adverse events were seen. Local reactions, febrile and crying episodes with the investigational vaccine (DTaP-IPV) were similar to the reactions seen with the existing DT-IPV vaccine. One month after completing the vaccination schedule, all children had antibodies above the defined protective antibody concentrations to polio, tetanus and diphtheria. For pertussis toxin, there was a significantly better response in the investigational vaccine group. We therefore conclude that, when used according to the schedule tested, the tetravalent DTaP-IPV vaccine is safe and immunogenic. In addition, the number of visits and the number of injections necessary are reduced with this vaccine and vaccination schedule.
Asunto(s)
Toxoide Diftérico/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina , Vacuna contra la Tos Ferina/inmunología , Vacuna Antipolio de Virus Inactivados/inmunología , Toxoide Tetánico/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Toxoide Diftérico/efectos adversos , Humanos , Lactante , Toxina del Pertussis , Vacuna contra la Tos Ferina/efectos adversos , Vacuna Antipolio de Virus Inactivados/efectos adversos , Toxoide Tetánico/efectos adversos , Vacunación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Factores de Virulencia de Bordetella/inmunologíaRESUMEN
This study was designed to examine the effects of in vivo hyperthermia on the circulating concentrations of a number of glucoregulatory hormones potentially involved in immunomodulation. Eight healthy male volunteers were immersed for 2 h in a hot water bath (water temperature 39.5 degrees C) (WI) during which period their rectal temperature rose to 39.5 degrees C. In a control study the subjects were immersed in thermoneutral water (water temperature 34.5 degrees C). Blood samples were collected before, at body temperature 38 degrees C (42.5 (30-52), median and range), minutes of hot WI, 39 degrees C (72.5 (58-97) minutes of hot WI), and 39.5 degrees C (at the end of 2 h of hot WI), as well as 1 and 2 h after cessation of 2 h of hot WI. In the control experiment blood samples were collected at identical time points. The growth hormone concentrations were elevated already at 38 degrees C to 24.2 (3.9-55.0) mU/l and peaked at 39 degrees C to 48.4 (20.8-81.5) mU/l compared to 0.3 (0.3-9.0) mU/l at baseline; at 39.5 degrees C the concentration declined to 31.6 (13.0-48.0) mU/l and further to 7.4 (0.8-17.3) mU/l 1 h after ending hot WI. The beta-endorphin levels were augmented at 39 degrees C and 39.5 degrees, to 8.0 (3.4-27.8) pmol/l and 8.1 (3.1-44.6) pmol/l, respectively, from 2.2 (0.7-5.6) pmol/l baseline. Glucagon levels raised from 23.0 (12.0-32.0) pmol/l to 32.0 (24.0-52.0) pmol/l at 39 degrees C, and to 38.5 (26.0-57.0) pmol/l at 39.0 degrees C. Insulin levels remained unchanged. Plasma glucose increased from 4.75 (4.2-7.6) mmol/l to 5.20 (4.6-5.6) mmol/l alone after 90 min of WI (temperature 39-39.5 degrees C). It is concluded that in vivo whole body WI hyperthermia increases the circulating levels of several essential glucoregulatory hormones.
Asunto(s)
Glucocorticoides/sangre , Hipertermia Inducida/métodos , Adyuvantes Inmunológicos/sangre , Adulto , Glucemia/metabolismo , Glucagón/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Hipertermia Inducida/efectos adversos , Inmersión/efectos adversos , Inmersión/fisiopatología , Insulina/sangre , Masculino , Estrés Fisiológico/sangre , Estrés Fisiológico/etiología , Estrés Fisiológico/inmunología , betaendorfina/sangreRESUMEN
OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from 920 to 2550 g. Controls were 37 term infants. METHODS: All infants were immunized with HibCP-TT at 2, 4 and 12 months of age. Antibodies to HibCP and TT were determined at each immunization and 1 month after the second and third. RESULTS: After two doses of HibCP-TT the preterm infants with GAs < or = 30 weeks (n = 8; mean GA, 29.5 weeks) had a significantly lower HibCP antibody response than the preterm infants with GAs > 30 weeks (n = 23; mean GA, 34.2 weeks) (P = 0.004), who for their part had a response not significantly different from that of the term infants. After the third dose there were no significant differences among the groups. The response to the TT part of the vaccine showed the same pattern. CONCLUSION: Although the most immature infants may show an inadequate antibody response to the initial immunizations, many preterm infants can benefit from vaccination with HibCP-TT when starting immunization at the same chronologic age as term infants.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/inmunología , Enfermedades del Prematuro/inmunología , Enfermedades del Prematuro/microbiología , Polisacáridos Bacterianos/inmunología , Anticuerpos Antibacterianos/análisis , Cápsulas Bacterianas/inmunología , Humanos , Lactante , Recién Nacido , Polisacáridos Bacterianos/administración & dosificación , Antitoxina Tetánica/análisis , Toxoide Tetánico/inmunología , Vacunas Conjugadas/inmunologíaRESUMEN
This work was designed to investigate the effect of in vivo hyperthermia in man on circulating immunoglobulin-secreting cells. Eight healthy male volunteers were immersed into a hot waterbath (WI) (water temperature 39.5 degrees C) for 2 h, whereby their body temperature rose to 39.5 degrees C. On another occasion they served as their own controls, being immersed into thermoneutral water (water temperature 34.5 degrees C) for 2 h. Blood samples were drawn before immersion, at body temperatures of 38, 39 and 39.5 degrees C, as well as 2 h after WI when their body temperatures were normalized. In the control experiments, blood samples were drawn at identical time points. A significant increase in the number of IgM-secreting cells per fixed number of blood mononuclear cells (BMNC) occurred 2 h after WI, whereas the number of IgA-secreting cells per fixed number of BMNC did not change. When the possible redistribution of BMNC was taken into account, the concentrations of IgM- and IgA-secreting cells (per ml blood) increased non-significantly during WI.
Asunto(s)
Células Productoras de Anticuerpos/inmunología , Fiebre/inmunología , Adulto , Temperatura Corporal/inmunología , Fiebre/sangre , Humanos , Inmunoglobulina A/biosíntesis , Inmunoglobulina M/biosíntesis , Recuento de Linfocitos , MasculinoRESUMEN
The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or DT alone in 51 healthy adults and 9 infants was studied. In adults, the isotypes of TT and DT AbSC were dominated by immunoglobulin G1 (IgG1) followed by IgG4 and IgA1. HibCP AbSC were dominated by the isotype IgA1 followed by (in decreasing order) IgG2, IgA2, IgM, and IgG1. The isotype distributions of TT and DT AbSC were independent of whether the toxoids were coupled to HibCP, and the isotypes of HibCP AbSC were not influenced by the nature of the carrier (TT or DT). Furthermore, the isotype distributions were unaffected by recent immunization with components of the conjugates, although this reduced the numbers of AbSC. The heavy-chain gene usage of HibCP AbSC in adults differed clearly from that in infants, which was restricted largely to the genes mu, gamma 1, and alpha 1, all lying upstream in the heavy-chain constant-region gene locus, while the usage in adults also, to different extents, involved the downstream genes gamma 2 and alpha 2. The ratio between the numbers of HibCP AbSC using heavy-chain genes from the downstream duplication unit (gamma 2, gamma 4, and alpha 2) and those using genes from the upstream duplication unit (gamma 3, gamma 1, and alpha 1) correlated with the preimmunization level of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Células Productoras de Anticuerpos/inmunología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae/inmunología , Cadenas Pesadas de Inmunoglobulina/biosíntesis , Isotipos de Inmunoglobulinas/biosíntesis , Polisacáridos Bacterianos/inmunología , Adulto , Factores de Edad , Cápsulas Bacterianas , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Lactante , Masculino , VacunaciónRESUMEN
The present work was designed to examine the effect of in vivo hyperthermia on the cell number and functions of polymorphonuclear leucocytes (PMN) and monocytes in human beings. Eight healthy volunteers were immersed into a waterbath (WI) (water temperature 39.5 degrees C) for 2 h, whereby their rectal temperature rose to 39.5 degrees C. On a later day they served as their own controls, being immersed into thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected before immersion, at body temperatures of 38, 39 and 39.5 degrees C as well as 2 h after water immersion. The neutrophil count was significantly increased at 39.5 degrees C, as well as 2 h after hot WI, compared with control. The monocyte count was significantly augmented at 38 and 39 degrees C and 2 h after hyperthermic load. The FMLP-induced chemiluminescence response, for a given number of PMN, was significantly reduced 2 h after hot WI. The total amount (per litre of blood) of superoxide production by PMN stimulated with opsonized zymosan (OZ) was significantly augmented at 39 and 39.5 degrees C and 2 h after WI. In vivo hyperthermia did not affect the function of monocytes, but when correlated to the changes in the concentrations of monocytes (response per litre blood) a significant increase in the phorbol myristate acetate (PMA)- and OZ-enhanced superoxide production occurred at 38 and 39 degrees C, as well as 2 h after termination of hot WI. Furthermore the OZ-enhanced monocyte chemiluminescence response per litre of blood was significantly enhanced 2 h after hot WI.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hipertermia Inducida , Monocitos/fisiología , Neutrófilos/fisiología , Adulto , Humanos , Recuento de Leucocitos , Mediciones Luminiscentes , Masculino , Monocitos/efectos de los fármacos , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/efectos de los fármacos , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Zimosan/farmacologíaRESUMEN
Vaccination of infants with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to carrier proteins has proven protective against invasive Hib diseases in several trials. However, insufficient immunogenicity has been noted in certain populations. Therefore, studies analyzing factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One hundred forty-four infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized into three groups that received TT as part of a diphtheria-tetanus-polio vaccine at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months (group C). Maternally acquired TT antibodies inhibited the anti-HibCP response to the first HibCP-TT dose in groups A and B (r = -0.5 and -0.4, respectively; P < 0.005). In these groups, infants with prevaccination anti-TT levels above the median failed to reach the defined long-term protective level of HibCP antibodies (1 microgram/ml) more often than infants with low prevaccination levels after the first (P = 0.0001) and the second (P = 0.01) doses of HibCP-TT. In contrast, active priming with TT at 4 months resulted in a threefold-higher median level of anti-HibCP (group C; 1.34 micrograms/ml) than in the unprimed group (group A; 0.40 microgram/ml) after the first dose of HibCP-TT (P = 0.01). Coadministration of TT had no enhancing effect (group B; 0.58 microgram/ml). No significant differences between the median anti-HibCP levels were seen after the second HibCP-TT dose (6.72, 9.63, and 11.44 micrograms/ml in groups A, B, and C, respectively; P = 0.25).
Asunto(s)
Vacunas contra Haemophilus/inmunología , Haemophilus influenzae/inmunología , Anticuerpos Antibacterianos/inmunología , Vacunas contra Haemophilus/administración & dosificación , Humanos , Inmunización Pasiva , Lactante , Recién Nacido , Polisacáridos Bacterianos/inmunología , Toxoide Tetánico/inmunologíaRESUMEN
This study was performed to examine the in vivo effects of a bolus of recombinant human growth hormone (r-hGH) on the human immune system. In a double blind placebo controlled cross over study, healthy volunteers were given 2 IU r-hGH as an intravenous infusion. r-hGH did not influence the subpopulations of blood mononuclear cells (BMNC), natural killer cell activity, in vitro proliferative responses or production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), TNF beta or interferon gamma in supernatants from BMNC stimulated with either lipopolysaccharide or phytohemagglutinin. However, two h after infusion a significant neutrocytosis occurred. It is concluded that a bolus infusion of r-hGH to healthy volunteers exerts only minor effects on the human immune system.
Asunto(s)
Hormona del Crecimiento/farmacología , Sistema Inmunológico/efectos de los fármacos , Adulto , Antígenos CD/análisis , Método Doble Ciego , Hormona del Crecimiento/administración & dosificación , Humanos , Infusiones Intravenosas , Interferón gamma/biosíntesis , Interleucinas/biosíntesis , Cinética , Recuento de Leucocitos , Activación de Linfocitos/efectos de los fármacos , Masculino , Neutrófilos/citología , Placebos , Proteínas Recombinantes/farmacología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
During the last five years increasing evidence has accumulated that many tumours classified as 'histiocytic' in the past do not originate from macrophages, but from transformed (or anaplastic) large lymphoid cells. Most of these studies have focused upon adult neoplasms. Knowledge concerning the lineage of 'histiocytic' tumours in the paediatric age group is more limited. In this study we have examined the clinical, morphological and immunophenotypical features of six childhood malignancies originally diagnosed as being of histiocytic origin. Three patients showed an aggressive course with involvement of internal organs and very short survival times. Two patients were brought into remission: one is alive without active disease after seven years; the other died after seven years due to treatment-related cardiomyopathy. The remaining patient had a protracted course for two and a half years, but subsequently deteriorated and died three years after diagnosis. The histomorphological features in five cases were those of anaplastic large cell lymphomas. The remaining case consisted of pleomorphic (rather than anaplastic) large lymphoid cells. In all cases the immunophenotypical examination showed features characteristic of activated T lymphocytes. All cases were positive for Ki-1 (CD30), and three were positive for epithelial membrane antigen (EMA). Histiocyte-associated markers were positive in residual reactive macrophages, but nowhere could unequivocal positivity for macrophage-associated markers be seen in the neoplastic cells. It is concluded that most childhood malignancies in the past classified as 'histiocytic' are examples of anaplastic large cell (Ki-1) lymphomas of T-cell type and that true histiocytic malignancies are exceedingly rare in the paediatric age group.
Asunto(s)
Sarcoma Histiocítico/clasificación , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células T/clasificación , Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Niño , Preescolar , Femenino , Sarcoma Histiocítico/inmunología , Sarcoma Histiocítico/patología , Humanos , Inmunofenotipificación , Lactante , Antígeno Ki-1 , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Masculino , Glicoproteínas de Membrana/análisis , Mucina-1RESUMEN
In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Vacunas Bacterianas/farmacología , Cloroquina/farmacología , Toxoide Diftérico/farmacología , Hipersensibilidad Tardía , Vacuna Antipolio de Virus Inactivados/farmacología , Proguanil/farmacología , Toxoide Tetánico/farmacología , Adulto , Anticuerpos Antivirales/análisis , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Masculino , Streptococcus pneumoniae/inmunologíaRESUMEN
Immuno-alkaline phosphatase (AP) staining for T cell subsets (CD4 and CD8) of smears from fingerprick blood functioned well under tropical climatic conditions when smears were stored frozen with silica gel before being labelled. Unlabelled smears were stored for up to 12 months and could be transferred abroad without antigenic damage. Identical total CD4 and CD8 counts were obtained on venous and capillary blood, when compared using a FACS analyser. Although the AP method gave somewhat higher total CD4 and CD8 counts, the ratio remained the same. The major advantages of the method are: (i) no expensive equipment is required, (ii) only minute amounts of blood are needed, and (iii) slides can be stored for long periods before labelling and can be preserved for later reading. The method is suitable for community studies where there is a need for assessing the immune status of the population.