Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt) was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation.

There is increasing evidence that green tea polyphenols can protect against myocardial damage. Recently, we showed that they bind to cardiac troponin C and alter myofilament Ca(2+) sensitivity in cardiac muscle. In the present study, we examined whether green tea extract (GTE) could prevent the progressive remodeling seen in ischemic myocardium and improve cardiac function by modulation of the contractile apparatus utilizing a myocardial infarction (MI) model in the rat involving ligation of the left anterior descending branch. Using this model, severe myocardial injury was found, including altered cardiac performance and the appearance of extensive fibrosis and left ventricular (LV) enlargement. Supplementation with 400 mg/kg/day of GTE for 4, 18, or 46 days had beneficial effects in preventing the hemodynamic changes. Histopathological studies showed that GTE attenuated the progressive remodeling seen after myocardial injury. Echocardiography confirmed that GTE prevented LV enlargement and improved LV performance in post-MI rats. In addition, we showed that GTE supplementation for 18 or 46 days increased the myofilament Ca(2+) sensitivity of the ischemic myocardium in post-MI rats. These results validate the novel action of green tea polyphenols in protecting against myocardial damage and enhancing cardiac contractility by modulating myofilament Ca(2+) sensitivity in post-MI rats.