RESUMO
For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
Assuntos
Adjuvantes Imunológicos , Bordetella pertussis , Imunoglobulina G , Células Th1 , Coqueluche , Bordetella pertussis/imunologia , Animais , Adjuvantes Imunológicos/administração & dosagem , Camundongos , Células Th1/imunologia , Coqueluche/imunologia , Coqueluche/prevenção & controle , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacina contra Coqueluche/imunologia , Vacina contra Coqueluche/administração & dosagem , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Toxoide Tetânico/imunologiaRESUMO
The disposition of illegal immigrants who lack social support and wish to return to their homeland is a frequent and difficult challenge for many mental health facilities in the United States. This case involved an undocumented Mexican patient with severe psychosis who was safely transferred to his hometown according to his and his family's wishes through the use of specific services provided by the Mexican Consulate. We hope that publication of this case will make the medical community more aware of the availability of these underused services, which can make a major difference in the prognosis of some undocumented patients who would otherwise be left without resources or appropriate care.