RESUMEN
CD46 (membrane cofactor protein), a complement-regulatory protein that participates in innate and acquired immunity, also serves as a receptor for viral and bacterial pathogens. CD46 isoforms terminate in one of two cytoplasmic tails, Cyt1 or Cyt2, which differ in signaling and trafficking properties. Dissecting the functions of the two cytoplasmic tails in these cellular processes has been hampered by the absence of specific reagents. Here we report the construction of Cyt1- and Cyt2-specific monoclonal antibodies (MAbs). These MAbs recognize unique epitopes within the tails and can be used for immunofluorescence microscopy, immunoblotting, and immunoprecipitation. Studies of Neisseria gonorrhoeae-infected cells with the CD46 tail MAbs demonstrate the differential recruitment of Cyt1 and Cyt2 to the cortical plaque.
Asunto(s)
Anticuerpos Monoclonales/metabolismo , Proteína Cofactora de Membrana/inmunología , Proteína Cofactora de Membrana/metabolismo , Neisseria gonorrhoeae/inmunología , Neisseria gonorrhoeae/aislamiento & purificación , Secuencia de Aminoácidos , Anticuerpos Monoclonales/biosíntesis , Adhesión Bacteriana/inmunología , Línea Celular Tumoral , Polaridad Celular/inmunología , Citoplasma/inmunología , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Humanos , Proteína Cofactora de Membrana/genética , Microscopía Fluorescente , Datos de Secuencia Molecular , Neisseria gonorrhoeae/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Isoformas de Proteínas/metabolismoRESUMEN
Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with >or=95% sensitivity and >or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.
Asunto(s)
Mpox/inmunología , Mpox/prevención & control , Vacuna contra Viruela/inmunología , Animales , Anticuerpos Antivirales , Reacciones Cruzadas , Brotes de Enfermedades , Reservorios de Enfermedades , Humanos , Mpox/transmisión , Sciuridae/virología , Linfocitos T/inmunología , Factores de Tiempo , Wisconsin/epidemiología , ZoonosisRESUMEN
Effective antibody responses are critical for protection against many human pathogens, including those with tropism for the respiratory tract (RT). Systemic immunoglobulin (Ig)G responses as well as mucosal IgA responses play complementary roles in protection against RT infections, and induction of a tissue-specific, isotype-appropriate humoral response is central to successful vaccination strategies. For respiratory virus infections in which current vaccines are either not available or not fully effective, antibody-mediated therapies may provide a viable treatment option. Prophylactic administration of polyclonal or monoclonal antibodies shows the best clinical efficacy, whereas therapeutic administration of antibodies after infection can also be highly protective but is greatly dependent on timing; efficacy declines soon after onset of disease symptoms. Further understanding of the mechanisms underlying antibody-mediated protection against respiratory virus infections may lead to improved immunization strategies as well as more effective antibody-based therapeutics.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/biosíntesis , Infecciones del Sistema Respiratorio/prevención & control , Vacunas Virales/uso terapéutico , Virosis/prevención & control , Anticuerpos Antivirales/sangre , Humanos , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Vacunación , Virosis/tratamiento farmacológico , Virosis/inmunologíaRESUMEN
PURPOSE: Human chorionic gonadotropin (hCG) is produced by colorectalcancers and may play a role in its progression. The clinical and immunological effects of a synthetic vaccine targeting beta-hCG composed of the COOH terminal peptide of beta-hCG (CTP37) conjugated to diphtheria toxoid (DT) was investigated in patients with metastatic colorectal cancer. EXPERIMENTAL DESIGN: Seventy-seven patients from 12 centers were randomly divided into two vaccine dose groups. CTP37-DT was formulated in an emulsion and administered i.m. on days 0, 28, and 70. Patients were evaluated for toxicity, overall survival, and antibody response to hCG and to DT. RESULTS: Immunizations were well tolerated with no patients requiring cessation of the injections. Anti-hCG antibody was detected in 56 of the 77 patients treated. Significant differences in antibody response and survival were not observed between the two dose groups. An intention-to-treat analysis of all vaccinated patients showed a median survival of 34 weeks. Patients who developed anti-hCG antibody levels higher than or equal to the median value exhibited a median survival of 45 weeks compared with 24 weeks for patients who developed anti-hCG antibody levels lower than the median (P = 0.0002). In contrast, no significant difference was observed when comparing survival based upon the level of DT antibody that developed (P = 0.80). CONCLUSIONS: Vaccination with CTP37-DT induced anti-hCG antibodies in most patients with advanced colorectal cancer. Anti-hCG antibody induction was associated with longer overall survival. CTP37-DT has an excellent safety profile and warrants further study in patients with colorectal cancer.