RESUMEN
1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation).
Asunto(s)
Anticuerpos Neutralizantes/metabolismo , Acrecentamiento Dependiente de Anticuerpo , Glicoproteínas de Membrana/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Proteínas del Envoltorio Viral/inmunología , Internalización del Virus , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Antivirales/metabolismo , Línea Celular Tumoral , Proteasas de Cisteína/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Monocitos , Peptidil-Dipeptidasa A/metabolismo , Receptores Fc/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Glicoproteína de la Espiga del Coronavirus , VacunasRESUMEN
OBJECTIVES: To describe the characteristics of patients in Hong Kong with or at risk of atherothrombosis, to determine the proportion of symptomatic patients with more than one vascular bed affected, and to assess the relationship between ankle brachial index and disease severity. DESIGN: Local participation in an international prevalence study. SETTING: Five centres in Hong Kong. PARTICIPANTS: A total of 210 subjects were recruited (105 women and 105 men). Patients were divided into the symptomatic group (with current or previous atherothrombotic symptoms, n=101) and at-risk group (with no current or previous symptoms, but aged over 55 years with at least two specified risk factors, n=109). MAIN OUTCOME MEASURES: Patient characteristics were described, including the number of arterial beds affected, ankle brachial index, presence of risk factors, and medications taken. RESULTS: Of the symptomatic patients, 30% had more than one arterial bed involved. A total of 55.4% of the symptomatic group and 18.4% of the at-risk group had abnormal ankle brachial index values. Lower ankle brachial indices were associated with a greater number of affected arterial beds. Diabetes mellitus and hypertension were the most prevalent risk factors in the at-risk group. Symptomatic patients were commonly treated with antihypertensive and antiplatelet agents, whereas at-risk patients were mostly treated with antihypertensive and antidiabetic agents. Only 20% of at-risk patients were taking antiplatelet agents. CONCLUSIONS: Ankle brachial index is a useful tool for predicting those at risk of atherothrombosis. This simple measurement can be used as part of the screening process in the general practice. The role of antiplatelet agents in primary prevention of atherothrombotic events in at-risk patients deserves further attention.