Biological challenges and technological opportunities for respiratory syncytial virus vaccine development

Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection, history of RSV vaccine-enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T-cell response patterns associated with enhanced disease. Live-attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials. Gene-based strategies, which can control the specificity and phenotypic properties of RSV-specific T-cell responses utilizing replication-defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV-specific antibody responses without induction of RSV-specific T-cell responses. These new technologies may allow development of vaccines that can protect against RSV-mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection.     

生物仿制药在全球的发展与机遇

 仿制药目前占据全球医药市场的重要份额，随着2001年第1个基因工程药物专利到期[1]，预计生物仿制药将在全球迅猛发展。对于中国、印度等创新能力较弱的国家，专利过期的生物仿制药无疑蕴藏着巨大的机遇。同时，欧美等生物制药产品发展领先的国家也不愿放弃生物仿制药的巨大市场，在生物仿制药的法规调整、审批和研制等方面已经开始实践。本文旨在介绍生物仿制药在欧美和我国的发展情况以及我国企业在开发生物仿制药领域的优势。...     

DNA vaccines for HIV: challenges and opportunities

In December 2005, the UNAIDS and WHO reported that the global epidemic known as acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25 million adults and children over the past 26 years. These figures included an estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to control the spread of human immunodeficiency virus (HIV) new infection rates are on the rise. An estimated 40.3 million people are now living with HIV, including 4.9 million new infections this past year. Nearly half of new HIV infections are in young people between the ages of 15 and 24. While drug therapies have helped sustain the lives of infected individuals in wealthy regions, they are relatively unavailable to the poorest global regions. This includes sub-Saharan Africa which has ∼25.8 million infected individuals, more than triple the number of infections of any other region in the world. It is widely believed that the greatest hope for controlling this devastating pandemic is a vaccine. In this review, we will discuss the current state of DNA-based vaccines and how they compare to other vaccination methods currently under investigation. We will also discuss innovative ideas for enhancing DNA vaccine efficacy and the progress being made toward developing an effective vaccine.     

Searching for genetic determinants of human aging and longevity: opportunities and challenges.

One way of testing possible causal relationships between various functional pathways and aging and longevity processes is to comparatively analyze groups of elderly individuals with select phenotypes for sequence variation in all genes participating in these pathways. Such direct association analysis to identify 'candidate pathways' in aging and longevity is theoretically feasible, with the complete sequence of the human genome known and massive gene annotation projects underway. To find all possible sequence variation of a large number of genes in aging populations, efficient genotyping methods are needed. Here, we describe the use of one such method, two-dimensional gene scanning (TDGS), for screening populations of centenarians and controls for polymorphic variation in the large BRCA1 breast cancer susceptibility gene.     

Ethical challenges in autism genomics: Recommendations for researchers

Equitable and just genetic research and clinical translation require an examination of the ethical questions pertaining to vulnerable and marginalized communities. Autism research and advocate communities have expressed concerns over current practices of genetics research, urging the field to shift towards paradigms and practices that ensure benefits and avoid harm to research participants and the wider autistic community. Building upon a framework of bioethical principles, we provide the background for the concerns and present recommendations for ethically sustainable and justice-oriented genetic and genomic autism research. With the primary goal of enhancing the health, well-being, and autonomy of autistic persons, we make recommendations to guide priority setting, responsible research conduct, and informed consent practices. Further, we discuss the ethical challenges particularly pertaining to research involving highly vulnerable individuals and groups, such as those with impaired cognitive or communication ability. Finally, we consider the clinical translation of autism genetics studies, including the use of genetic testing. These guidelines, developed by an interdisciplinary working group comprising autistic and non-autistic individuals, will aid in leveraging the potential of genetics research to enhance the quality of life of autistic individuals and are widely applicable across stigmatized traits and vulnerable communities.     

Human-hemato-lymphoid-system mice: opportunities and challenges

With the recent advances in human-hemato-lymphoid-system mice, this commentary discusses the utility of these mice and further improvements required to generate an accessible system that allows predictive in vivo human hematology and immunology research.     

Tissue engineering: challenges and opportunities

This article reviews the key developments in the tissue engineering field over the past several years. The issues related to the development of the components of tissue-engineered products including cells, biomaterials, and biomolecules, and their integration into safe and effective products are presented. Moreover, the article outlines the challenges to the commercialization of tissue-engineered products, and highlights the ongoing efforts by the American Society for Testing and Materials (ASTM) in developing standards for tissue-engineered medical products. Furthermore, funding opportunities at the Advanced Technology Program at NIST are presented. Published 2000 John Wiley & Sons, Inc.     

Carbohydrate-based vaccines: challenges and opportunities

Advances in the synthesis of oligo- or polysaccharides and new technologies developed in glycobiology studies have opened a new avenue in carbohydrate vaccine design. In principle, various types of cell-surface epitopes, characteristic of the invading organism or related to aberrant growth of cells, can be applied to develop vaccines. Numerous promising carbohydrate-based vaccine candidates have been prepared in recent years. This article, primarily for general readers, briefly presents the recent advances involving carbohydrate-based vaccines, including antibacterial, antiparasite, anticancer and antivirus vaccines.     

Veterinary immunology: opportunities and challenges.

The 6th International Veterinary Immunology Symposium (6IVIS) was held in Uppsala, Sweden from 15-20 July 2001.     

Competency-based residency training in pathology: challenges and opportunities

The Accreditation Council for Graduate Medical Education (ACGME) is requiring that all medical specialties adopt a new paradigm for residency education: competency-based residency education. Competency-based education includes not only the acquisition of knowledge and the demonstration of safe medical practice, but also competency in practice-based learning, practice improvement, interpersonal skills and communication, professionalism, and an awareness of pathology's role in a larger health care system. Implementation of this new training program will require new educational resources and the implementation of new faculty and resident skills and incentives.     

Genomic and metagenomic challenges and opportunities for bioleaching: a mini-review

High-throughput genomic technologies are accelerating progress in understanding the diversity of microbial life in many environments. Here we highlight advances in genomics and metagenomics of microorganisms from bioleaching heaps and related acidic mining environments. Bioleaching heaps used for copper recovery provide significant opportunities to study the processes and mechanisms underlying microbial successions and the influence of community composition on ecosystem functioning. Obtaining quantitative and process-level knowledge of these dynamics is pivotal for understanding how microorganisms contribute to the solubilization of copper for industrial recovery. Advances in DNA sequencing technology provide unprecedented opportunities to obtain information about the genomes of bioleaching microorganisms, allowing predictive models of metabolic potential and ecosystem-level interactions to be constructed. These approaches are enabling predictive phenotyping of organisms many of which are recalcitrant to genetic approaches or are unculturable. This mini-review describes current bioleaching genomic and metagenomic projects and addresses the use of genome information to: (i) build metabolic models; (ii) predict microbial interactions; (iii) estimate genetic diversity; and (iv) study microbial evolution. Key challenges and perspectives of bioleaching genomics/metagenomics are addressed.     

Synthetic carbohydrate-based antitumor vaccines: challenges and opportunities

The development of a clinically effective, carbohydrate-based antitumor vaccine is a longstanding ambition in the prevention and treatment of cancer. This review seeks to provide a discussion of some of the unique challenges facing this particular field of immunology. The authors present a historic account of their ongoing research program devoted to the development of fully synthetic, carbohydrate-based anticancer vaccines of clinical value. As will be seen, remarkable advances in carbohydrate and glycopeptide assembly techniques have allowed for the preparation of synthetic constructs of progressively increasing structural complexity. The authors describe the evolution of their synthetic carbohydrate program from first-generation constructs, which were monovalent in nature, to highly complex unimolecular multivalent vaccines, in which multiple carbohydrate antigens are displayed in the context of a single polypeptide backbone. It is the hope that each generation of vaccines represents a move closer to achieving the ultimate objective of developing broadly useful, robust anticancer vaccines.     

Chronic hepatitis B in pregnancy: unique challenges and opportunities

Chronic hepatitis B (CHB) affects 350 million individuals worldwide. Perinatal transmission leads to high rates of chronic infection and complications, including cirrhosis and hepatocellular carcinoma. It is important to recognize and appropriately treat CHB in pregnancy, thereby reducing the risk of neonatal transmission and HBV-associated morbidity and mortality. Screening for CHB is recommended in all pregnant mothers as is universal vaccination of infants with hepatitis B virus (HBV) vaccine with or without hepatitis B immunoglobulin (HBIG). This has resulted in a lower incidence of HBsAg seropositivity and HCC in regions where universal infant vaccination has been endorsed. Mode of delivery and breastfeeding do not appear to affect HBV transmission rates based on available data. Overall, CHB does not increase perinatal maternal-fetal mortality. Administration of oral antiviral therapy during the third trimester to HBsAg-positive mothers with HBV DNA≥7 log IU/mL may be useful in preventing breakthrough infection. Treatment may be considered earlier in pregnancy for persistently active liver disease shown by high ALT, HBV DNA levels and/or significant hepatic fibrosis. Lamivudine, tenofovir and telbivudine are safe and effective and are the agents of choice in pregnancy. However, further clinical studies are necessary to elucidate the role of antiviral therapy in the pregnant HBV carrier.     

Epigenetics and bipolar disorder: new opportunities and challenges

Despite significant effort, understanding of the molecular causes and mechanisms of bipolar disorder (BD) remains a major challenge. Numerous molecular genetic linkage and association studies have been conducted over the last two decades; however, the data are quite inconsistent or even controversial. This article develops an argument that molecular studies of BD would benefit significantly from adding an epigenetic (epiG) perspective. EpiG factors refer to modifications of DNA and chromatin that "orchestrate" the activity of the genome, including regulation of gene expression. EpiG mechanisms are consistent with various non-Mendelian features of BD such as the relatively high degree of discordance in monozygotic (MZ) twins, the critical age group for susceptibility to the disease, clinical differences in males and females, and fluctuation of the disease course, including interchanges of manic and depressive phases, among others. Apart from the phenomenological consistency, molecular epiG peculiarities may shed new light on the understanding of controversial molecular genetic findings. The relevance of epigenetics for the molecular studies of BD is demonstrated using the examples of genetic studies of BD on chromosome 11p and the X chromosome. A spectrum of epiG mechanisms such as genomic imprinting, tissue-specific effects, paramutagenesis, and epiG polymorphism, as well as epiG regulation of X chromosome inactivation, is introduced. All this serves the goal of demonstrating that epiG factors cannot be ignored anymore in complex phenotypes such as BD, and systematic large-scale epiG studies of BD have to be initiated.