RESUMO
Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.
Assuntos
Aciltransferases/administração & dosagem , Antígenos de Bactérias/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Imunidade nas Mucosas/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Vacinas contra a Tuberculose/administração & dosagem , Tuberculose Pulmonar/prevenção & controle , Aciltransferases/genética , Aciltransferases/imunologia , Administração Intranasal , Aerossóis , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Feminino , Cobaias , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Pulmão/imunologia , Pulmão/microbiologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Mucosa Nasal/imunologia , Mucosa Nasal/microbiologia , Temperatura , Fatores de Tempo , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Vacinação , Vacinas de DNA/administração & dosagemRESUMO
Immunity declines with advancing age. Lymphocyte proliferation, natural killer cell activity, and antibody response to tetanus toxoid vaccination were evaluated in cohorts of rhesus monkeys (Macaca mulatta) aged 2-36 years in order to characterize senescent changes in immune function. The results were analyzed in accordance with host age. Lymphocyte proliferation was generally low in older monkeys, especially males. Lymphocytes from old male monkeys responded significantly less to test mitogens than did those of old female (P<.05) or young males and females (P<.01). Natural killer cell function was similarly decreased in old monkeys; however, for this function there was no apparent gender difference. Antibody response to tetanus vaccine was less in older monkeys but was also low in several of the younger moskeys. These data confirm our expectation that, like other mammalian species, the rhesus monkey shows a decline in immune function with age and demonstrate further that the changes are more marked in males. Rhesus monkeys, therefore, are suitable for the investigation of mechanisms of immune senescence.
