Vaccines against gonorrhea: Current status and future challenges

Gonorrhea occurs at high incidence throughout the world and significantly impacts reproductive health and the spread of human immunodeficiency virus. Current control measures are inadequate and seriously threatened by the rapid emergence of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however, recent advances justify significant effort in this area. Conserved vaccine antigens have been identified that elicit bactericidal antibodies and, or play key roles in pathogenesis that could be targeted by a vaccine-induced response. A murine genital tract infection model is available for systematic testing of antigens, immunization routes and adjuvants, and transgenic mice exist to relieve some host restrictions. Furthermore, mechanisms by which Neisseria gonorrhoeae avoids inducing a protective adaptive response are being elucidated using human cells and the mouse model. Induction of a Th1 response in mice clears infection and induces a memory response, which suggests Th1-inducing adjuvants may be key in vaccine-induced protection. Continued research in this area should include human testing and clinical studies to confirm or negate findings from experimental systems and to define protective host factors.     

TRIB1的研究进展

TRIB1属于人类TRIB家族，是促分裂原活化蛋白激酶（mitogen·activatedproteinkinase，MAPK）途径级联控制的调节蛋白，在多种组织中表达，与骨髓恶性肿瘤、卵巢癌、动脉粥样硬化及组织移植密切相关。此文就TRIB1的起源、家族、结构、功能、参与的信号途径及相关疾病作一综述。     

Mechanisms of liver involvement in systemic disease

The liver may be injured during the course of many systemic diseases. The mechanisms of injury can be broadly divided into four pathways: vascular, toxic, immune, and hormonal. Vascular obstruction may be an early event but is also the late common pathway from all mechanisms. Despite the large number of possible initiating factors, the end results are few, including death of hepatocytes or cholangiocytes, leading to the stereotyped syndromes of acute liver failure, non-cirrhotic portal hypertension, or cirrhosis. This small number of outcomes is a reflection of the few anatomic patterns that can be generated by microvascular obstruction. Vascular obstruction may occur by thrombosis, inflammation, or congestive injury. The innate immunity pathway is activated by endotoxin and other agents, leading to inflammatory infiltration, release of cytokines and reactive oxygen species, and necrosis. The adaptive immune pathway involves the generation of antibodies and antigen-specific cell-mediated attack on hepatic cells. Hormonal effects are principally involved when overnutrition leads to hyperinsulinemia followed by hepatocellular necrosis.     

Determinants of measles seroprevalence among pregnant women in Paris,France

Non-immune pregnant women are at risk of severe measles. As the measles vaccination is contraindicated during pregnancy, women should be vaccinated before conception or during the postpartum period. Nevertheless, measles serology is not recommended during pregnancy in France, and there are no data available concerning measles susceptibility and its associated risk factors among pregnant women. The socio-demographic determinants of measles seronegativity have been identified in a prospective cohort of 826 pregnant women in Paris, France. Measles seronegativity was 10.41% (95% CI 8.32–12.50). Women from higher socio-economic groups, born in France after 1980, were more frequently seronegative.     

4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.     

Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection

Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior influenza virus exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness. We first tested whether it was possible to use Advax to obtain single-dose vaccine protection of neonatal pups against lethal influenza infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single subcutaneous immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels and was associated with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells. Pups immunized with Advax had significantly higher splenocyte influenza-stimulated IFN-γ, IL-2, IL-4, and IL-10 production by CBA and a 3–10 fold higher frequency of IFN-γ, IL-2, IL-4 or IL-17 secreting T cells by ELISPOT. Immunization with iH1N1 + Advax induced robust protection of pups against virus challenge 3 weeks later, whereas pups immunized with iH1N1 antigen alone had no protection. Protection by Advax-adjuvanted iH1N1 was dependent on memory B cells rather than memory T cells, with no protection in neonatal μMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting ongoing development of Advax™ as a neonatal vaccine adjuvant.