RESUMEN
BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Inmunogenicidad Vacunal , SARS-CoV-2 , Vacunas de Productos Inactivados/efectos adversos , Pueblos de Medio Oriente , Emiratos Árabes Unidos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
Background: This study was designed to explore the effects of flaxseed oil on the metaphase II (MII) oocyte rates in women with decreased ovarian reserve (DOR). Methods: The women with DOR were divided into a study group (n = 108, flaxseed oil treatment) and a control group (n = 110, no treatment). All patients were treated with assisted reproductive technology (ART). Subsequently, the ART stimulation cycle parameters, embryo transfer (ET) results, and clinical reproductive outcomes were recorded. The influencing factors affecting the MII oocyte rate were analyzed using univariate analysis and multivariate analysis. Results: Flaxseed oil reduced the recombinant human follicle-stimulating hormone (r-hFSH) dosage and stimulation time and increased the peak estradiol (E2) concentration in DOR women during ART treatment. The MII oocyte rate, fertilization rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate were increased after flaxseed oil intervention. The embryo implantation rate of the study group was higher than that of the control group (p = 0.05). Additionally, the female age [odds ratio (OR): 0.609, 95% confidence interval (CI): 0.52-0.72, p < 0.01] was the hindering factor of MII oocyte rate, while anti-Müllerian hormone (AMH; OR: 100, 95% CI: 20.31-495, p < 0.01), peak E2 concentration (OR: 1.00, 95% CI: 1.00-1.00, p = 0.01), and the intake of flaxseed oil (OR: 2.51, 95% CI: 1.06-5.93, p = 0.04) were the promoting factors for MII oocyte rate. Conclusion: Flaxseed oil improved ovarian response and the quality of oocytes and embryos, thereby increasing the fertilization rate and high-quality embryo rate in DOR patients. The use of flaxseed oil was positively correlated with MII oocyte rate in women with DOR. Clinical trial number: https://www.chictr.org.cn/, identifier ChiCTR2300073785.
Asunto(s)
Aceite de Linaza , Reserva Ovárica , Femenino , Humanos , Suplementos Dietéticos , Transferencia de Embrión/métodos , Fertilización In Vitro , Aceite de Linaza/farmacología , Metafase , OocitosRESUMEN
AIM: To study the mechanism responsible for alteration of T cell response in IDDM patients. METHODS: T cells from peripheral blood of IDDM patients were activated by anti-TCR antibodies. The level of TCR-mediated signaling pathway was analyzed. RESULTS: T cells from IDDM patients responded weakly to anti-TCR antibody-induced proliferation, as compared with T cells from normal subjects (P < 0.05). The defect could be partially remedied by the addition of rIL-2, while the anti-CD28 antibody stimulation did not restore the proliferative response of anti-TCR-induced cells from IDDM patients (P = 0.03). CONCLUSION: Unresponsiveness of the T cells from IDDM patients to anti-TCR antibody may result from a defect in the signaling pathway, the CD28 co-stimulation-signaling pathway is normal. Defect in the TCR signaling pathway increases the sensitivity of T cells from IDDM patients to apoptosis or anergy.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Diabetes Mellitus Tipo 1/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Transducción de Señal , Linfocitos T/inmunología , Antígenos CD28/inmunología , Proliferación Celular , Células Cultivadas , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Activación de Linfocitos , Linfocitos T/citología , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
OBJECTIVE: To investigates the surgical treatment for congenital anophthalmia. METHODS: The operation was performed in two steps. At first, the orbit was enlarged and the tarsus was reconstructed with cartilage transplantation. At the second step, blepharoptosis was corrected with levator shortening or frontalis muscle suspension. RESULTS: Five cases have been treated successfully with this method and satisfactory results were obtained. CONCLUSION: Orbit amplification and tarsus reconstruction along with ptosis correction is an effective treatment for anophthalmia both aesthetically and functionally.
Asunto(s)
Anoftalmos/cirugía , Blefaroptosis/cirugía , Blefaroplastia , Blefaroptosis/congénito , Cartílago/trasplante , Músculos Faciales/cirugía , Humanos , Músculos Oculomotores/cirugía , Órbita/cirugía , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) is an important human pathogen that causes chronic liver disease worldwide. It is desirable to develop vaccines to prevent HCV infection, or at least to prevent progression to chronicity. We once constructed an optimized hepatitis C virus core and envelope 2 fusion antigen DNA vaccine, which could induce humoral and cellular immune responses against HCV core and E2 protein in BALB/c mice efficiently. Flt3 (Fms-like tyrosine kinase 3) -ligand has been identified as an important cytokine for the generation of professional antigen-presenting cells, particularly dendritic cells. We reasoned that a DNA vaccine coexpressing the antigen and FL may activate immune responses more effectually. In this study, The influence of FL on this HCV DNA vaccine was evaluated. The cDNA encoding signal peptide and extracellular domain of murine FL was inserted into the plasmid pST-CE2t, and the resulting plasmid pST-CE2t/FL was transfected into COS7 cells. The HCV core and E2 protein were detected by Western blotting, and the soluble murine FL was detected by ELISA. Eight-week-old female BALB/c mice were inoculated intramuscularly with 100 microg pST-CE2t, pST-CE2t/FL or mock vector, respectively, and boosted at the same dosage 3 weeks later. Anti-HCV core and E2 total IgG and isotypes were measured at weeks 1,3,5,7. Splenocyte proliferative response to recombinant HCV core and E2 protrein were detected at week 7. SP2/0 cells expressing HCV core protein were used as target cells for the detection of cytotoxic T lymphocyte (CTL) response. Western blot analysis showed that a protein band with molecular weight about 70 kD from lysate of COS7 cells transfected with plasmid pST-CE2t/FL could be detected by anti-HCV core or E2 monoclonal antibodies, which indicated that pST-CE2t could express glucosylated HCV core and E2 fusion protein. Murine FL could be detected in the culture supernatant of COS7 cells transfected with pST-CE2t/FL. Plasmid pST-CE2t immunized mice developed higher anti-HCV core and E2 IgG seroconversion rates and titers than pST-CE2t/FL group did at different various times, but the IgG2a/IgG1 ratio of anti-HCV E2 protein in pST-CE2t/FL group is much higher than pST-CE2t group. Splenocytes from pST-CE2t or pST-CE2t/FL immunized mice could proliferate with stimulation of HCV core or E2 protein in vitro, although pST-CE2t/FL group showed much stronger response. Splenocytes from mice immunized with pST-CE2t/FL induced 79.03% +/- 9.95% of target cell lysis at the effector/target ratio of 100:1, which was significantly greater than the lysis (62.2% +/- 8.62%) observed in mice immunized with pST-CE2t. Our data demonstrated that the incorporation of FL can preferentially enhance the cellular response to this HCV fusion antigen DNA vaccine. In contrast, HCV specific antibodies were inhibited by FL in vaccinated mice. More and more data supports that recovery from acute HCV infection may depend upon the generation of broad-based cellular immune responses to viral proteins. So, FL may be of potential value as an adjuvant in the development of DNA-based immunization for prophylactic and therapeutic vaccine against HCV infection.