A recombinant rabies virus chimera expressing the DC-targeting molecular MAB2560 shows enhanced vaccine immunogenicity through activation of dendritic cells.

BACKGROUND: Rabies, caused by the rabies virus (RABV), is an ancient and neglected zoonotic disease posing a large public health threat to humans and animals in developing countries. Immunization of animals with a rabies vaccine is the most effective way to control the epidemic and the occurrence of the disease in humans. Therefore, the development of cost-effective and efficient rabies vaccines is urgently needed. The activation of dendritic cells (DCs) is known to play an important role in improving the host immune response induced by rabies vaccines. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we constructed a recombinant virus, rCVS11-MAB2560, based on the reverse genetic system of the RABV CVS11 strain. The MAB2560 protein (a DC-targeting molecular) was chimeric expressed on the surface of the viral particles to help target and activate the DCs when this virus was used as inactivated vaccine. Our results demonstrated that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, the inactivated recombinant virus rCVS11-MAB2560 could produce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs more quickly than rCVS11 post immunization. CONCLUSIONS/SIGNIFICANCE: In summary, the recombinant virus rCVS11-MAB2560 chimeric-expressing the molecular adjuvant MAB2560 can stimulate high levels of humoral and cellular immune responses in vivo and can be used as an effective inactivated rabies vaccine candidate.

Regulation of innate immune responses by rabies virus.

Rabies virus (RABV) is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals, posing a great threat to people and public safety. It is well known that innate immunity is the critical first line of host defense against viral infection. It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors, leading to the production of type I interferons (IFNα/ß), inflammatory cytokines, and chemokines, or the activation of autophagy or apoptosis to inhibit virus replication. In the case of RABV, the innate immune response is usually triggered when the skin or muscle is bitten or scratched. However, RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system (CNS). Once RABV reaches the CNS, it cannot be wiped out by the immune system or any drugs. Therefore, a better understanding of the interplay between RABV and innate immunity is necessary to develop effective strategies to combat its infection. Here, we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.

X-linked congenital adrenal hypoplasia: a case presentation.

BACKGROUND: Most patients with congenital adrenal hypoplasia (AHC) develop symptoms during infantile and juvenile periods, with varying clinical manifestations. AHC is a disease that is easily misdiagnosed as Addison's disease or congenital adrenal hyperplasia (CAH). There was also a significant time difference between the age at which patients developed symptoms and the age at which they were diagnosed with AHC. Most patients showed early symptoms during infantile and juvenile periods, but were diagnosed with AHC many years later. CASE PRESENTATION: We are currently reporting a male patient who developed systemic pigmentation at age 2 and was initially diagnosed with Addison's disease. At 22 years of age, he experienced a slipped capital femoral epiphysis (SCFE), a disease mostly seen in adolescents aged 8-15 years, an important cause of which is endocrine disorder. Testes evaluated using color Doppler Ultrasonography suggested microcalcifications. Further genetic testing and auxiliary examinations revealed that the patient had hypogonadotropic hypogonadism (HH) and DAX-1 gene disorders, at which time he was diagnosed with AHC complicated by HH. He was given hormone replacement therapy, followed by regular outpatient review to adjust the medication. CONCLUSIONS: The typical early symptoms of AHC are hyperpigmentation and ion disturbance during infantile and juvenile periods, while few patients with AHC develop puberty disorders as early symptoms. AHC is prone to being misdiagnosed as Addison's disease, and then gradually develops the symptoms of HH in adolescence. The definitive diagnosis of AHC ultimately is based on the patient's clinical presentation, laboratory results and genetic testing results.

Effect of Elevated Ketone Body on Maternal and Infant Outcome of Pregnant Women with Abnormal Glucose Metabolism During Pregnancy.

Ketone bodies are one of the products of fat metabolism which can be used as an alternative energy source for the human body in states of glucose deficiency. Normal pregnant women may develop ketosis due to physiological changes during pregnancy, while pregnant women with abnormal glucose metabolism are more likely to develop ketosis due to abnormal insulin secretion. Animal experiments and clinical studies have shown that exposure to high-ketone environments during pregnancy is closely related to adverse maternal and infant outcomes. However, there is no unified conclusion on whether ketone bodies should be routinely monitored during pregnancy. This review summarizes the existing studies on ketone body levels and pregnancy outcomes in the case of abnormal blood glucose during pregnancy, elaborates the current guidelines on the level of ketone bodies, provides the detection and treatment of ketosis in pregnant women with abnormal blood glucose in the clinical practice.

Research Progress on the Experimental Animal Model of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) refers to different degrees of abnormal glucose metabolism during pregnancy, where blood glucose levels do not reach the level of overt diabetes, accounting for 80-90% of pregnancy with hyperglycemia. Hyperglycemia affects the pregnancy process, leading to a series of adverse maternal outcomes that have a profound impact on the future of the offspring. The establishing of an appropriate GDM model will provide theoretical basis for study GDM pathogenesis involves, the choice of resonable drugs and the observation the disease trends and outcomes. At present, there are many methods for establishing experimental GDM animal models and animal choices. This paper examines the different GDM models and their induction methods.

A Review of Research Progress on Glycemic Variability and Gestational Diabetes.

Gestational diabetes mellitus (GDM) is associated with many adverse obstetric outcomes and neonatal outcomes, including preeclampsia, Cesarean section, and macrosomia. Active screening and early diabetes control can reduce the occurrence of adverse outcomes. Glycosylated hemoglobin (HbA1c) only reflects average blood glucose levels, but not glycemic variability (GV). Studies have shown that GV can cause a series of adverse reactions, and good control of GV can reduce the incidence of adverse pregnancy outcomes in patients with GDM. In order to provide clinicians with a better basis for diagnosis and treatment, this study reviewed the measurement, evaluation, and control of GV, the importance of GV for patients with GDM, and correlations between GV and maternal and neonatal outcomes.