RESUMEN
Streptococcus pneumoniae infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective protein-based alternative. We and others have shown that immunization with pneumococcal lipoproteins that lack the lipid anchor protects against colonization. Since immunity against S. pneumoniae is mediated through Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects of a lipid modification on the induced immune responses in either intranasally or subcutaneously vaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrA strongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhanced antibody concentrations and different induction kinetics. The induced humoral immune response was modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-type immunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderate but consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins, indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus, protein lipidation represents a promising approach for the development of a serotype-independent pneumococcal vaccine.
RESUMEN
Aparte de la importancia para el fisiólogo, la triyodotironina es de valor para el clínico. Uno de sus usos es en el diagnóstico del hipertiroidismo y en descubrir el bocio nodular no tóxico con nódulos activos. Otro uso es en el tratamiento del hipotiroidismo. Se han sugerido otras indicaciones, pero no se ha confirmado aún su eficacia. Se han comunicado tratamientos con éxito de pacientes hipotiroideos resistentes que no respondieron a la administración oral de tiroides desecada. Se ha sostenido que algunos casos de oligozoospermia masculina han mejorado consecutivamente a la administración del triyodotiroinina. Finalmente, se ha hecho aumentar el metabolismo basal en algunos pacientes con metabolismo disminuido pero sin hipotiroidismo. Estos resultados, sin embargo, requieren una evaluación crítica severa por medio del estudio de gran número de pacientes a los que se les administre la hormona y una sustancia testigo antes de que puedan admitirse en la práctica.
Apart from its importance to the physiologist, triiodothyroine has been of value to the clinician. One use has been in the diagnosis of hyperthyroidism and in the detection of nontoxic nodular goiter with "bot" or active nodules. Another has been in the treatment of hypothyroidism. Further indications have been suggested but efficacy has not yet been confirmed. Claims have been made for the successful treatment of resistant hypothyroid patients who did not respond to desiccated thyroid by mouth. Some instances of male oligozzospermia have been said to improve following triiodothyronine administration. Finally the basal metabolic rate has been made to increase in some patients with hypometabolism but without hypothyroidism. However, such claims require very critical appraisal by means of large series of patients receiving both hormone and a placebo, before they can be admitted into practice.
