RESUMEN
To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , SARS-CoV-2/inmunología , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/inmunología , Animales , Animales Modificados Genéticamente , Vacunas contra la COVID-19/administración & dosificación , Femenino , Células HEK293 , Humanos , Células K562 , Macaca mulatta , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Primates , Organismos Libres de Patógenos Específicos , Glicoproteína de la Espiga del Coronavirus/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación/métodos , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Phosphate starvation leads to a strong reduction in shoot growth and yield in crops. The reduced shoot growth is caused by extensive gene expression reprogramming triggered by phosphate deficiency, which is not itself a direct consequence of low levels of shoot phosphorus. However, how phosphate starvation inhibits shoot growth in rice is still unclear. In this study, we determined the role of OsCYCP4s in the regulation of shoot growth in response to phosphate starvation in rice. We demonstrate that the expression levels of OsCYCP4s, except OsCYCP4;3, were induced by phosphate starvation. Overexpression of the phosphate starvation induced OsCYCP4s could compete with the other cyclins for the binding with cyclin-dependent kinases, therefore suppressing growth by reducing cell proliferation. The phosphate starvation induced growth inhibition in the loss-of-function mutants cycp4;1, cycp4;2, and cycp4;4 is partially compromised. Furthermore, the expression of some phosphate starvation inducible genes is negatively modulated by these cyclins, which indicates that these OsCYCP4s may also be involved in phosphate starvation signaling. We conclude that phosphate starvation induced OsCYCP4s might coordinate phosphate starvation signaling and cell cycle progression under phosphate starvation stress.
Asunto(s)
Ciclo Celular , Oryza/citología , Oryza/metabolismo , Fosfatos/deficiencia , Proteínas de Plantas/metabolismo , Transducción de Señal , Proliferación Celular/genética , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Mutación con Pérdida de Función/genética , Oryza/genética , Fenotipo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Brotes de la Planta/crecimiento & desarrollo , Biosíntesis de Proteínas , Transcripción GenéticaRESUMEN
OBJECTIVE: To explore an efficacious protocol for the patients with acute promyelocytic leukemia (APL) after a complete remission (CR) by all-trans retinoic acid (ATRA). METHODS: A total of 32 APL patients with an induction of CR by ATRA at our hospital from January 2000 to October 2007 received conventional standard chemotherapy as a consolidation regimen. Stratified according to age, those under 50 years old received an intermediate dose of cytarabine(IDAra-C)and over 50 years old non-IDAra-C regimen. Maintenance regimen: all patients received ATRA, arsenic trioxide (As2O3) and 6-mercaptopurine (6-MP) + methotrexate (MTX) alternately and sequentially for 3 years. The efficacy and side effects of these chemotherapies were observed. RESULTS: The median follow-up was 72 (40 - 124) months. The 5-year disease-free survival (DFS) rates of under 50 years old and over 50 years old were 94.7% and 92.3% respectively. The difference was statistically insignificant (P > 0.05). One patient relapsed after a consolidation therapy and so did another on a maintenance regimen. Thirty patients achieved a constant CR. And 16 of 30 patients completed chemotherapy beyond 5 years and survived disease-free. The 5-year DFS rate of 32 patients was 93.8%. CONCLUSION: After the achievement of CR with ATRA, all APL patients have a higher rate of DFS after stratification. The side effects are generally mild. Thus a stratification therapy is both feasible and efficacious.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Leucemia Promielocítica Aguda/terapia , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
To achieve the complete remission (CR), acute leukemia (AL) patient must get through the period of myeloid ablation after chemotherapy that the white blood cell (WBC) count in peripheral blood decreases rapidly. To observe the relationship of WBC count with therapeutic effectiveness after chemotherapy in previously untreated AL, eighty cases of previously untreated acute leukemia who took the first induction chemotherapy course were analyzed. Blood routine was carried out 2 to 3 times every week while the bone marrow pictures on 12th and 20th day after chemotherapy were observed. 80 patients were divided into 3 groups based on the lowest value of WBC count after chemotherapy: